Electron Dynamics in Alkane C-H Activation Mediated by Transition Metal Complexes.

Alkanes, ideal raw materials for industrial chemical production, typically exhibit limited reactivity due to their robust and weakly polarized C-H bonds. The challenge lies in selectively activating these C-H bonds under mild conditions. To address this challenge, various C-H activation mechanisms have been developed. Yet, classifying these mechanisms depends on the overall stoichiometry, which can be ambiguous and sometimes problematic. In this study, we utilized density functional theory calculations combined with intrinsic bond orbital (IBO) analysis to examine electron flow in the four primary alkane C-H activation mechanisms: oxidative addition, σ-bond metathesis, 1,2-addition, and electrophilic activation. Methane was selected as the representative alkane molecule to undergo C-H heterolytic cleavage in these reactions. Across all mechanisms studied, we find that the CH3 moiety in methane consistently uses an electron pair from the cleaved C-H bond to form a σ-bond with the metal. Yet, the electron pair that accepts the proton differs with each mechanism: in oxidative addition, it is derived from the d-orbitals; in σ-bond metathesis, it resulted from the metal-ligand σ-bonds; in 1,2-addition, it arose from the π-orbital of the metal-ligand multiple bonds; and in electrophilic activation, it came from the lone pairs on ligands. This detailed analysis not only provides a clear visual understanding of these reactions but also showcases the ability of the IBO method to differentiate between mechanisms. The electron flow discerned from IBO analysis is further corroborated by results from absolutely localized molecular orbital energy decomposition analysis, which also helps to quantify the two predominant interactions in each process. Our findings offer profound insights into the electron dynamics at play in alkane C-H activation, enhancing our understanding of these critical reactions.

Mucoadhesive, antioxidant, and lubricant catechol-functionalized poly(phosphobetaine) as biomaterial nanotherapeutics for treating ocular dryness.

Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.

Stimulatory Action of Telmisartan, an Antagonist of Angiotensin II Receptor, on Voltage-Gated Na⁺ Current: Experimental and Theoretical Studies.

Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this agent has any direct effects on ion currents remains unexplored. In whole-cell current recordings, addition of Tel increased the peak amplitude of voltage-gated Na⁺ (NaV) current (INa) accompanied by the increased time constant of INa inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated INa in these cells is unlinked to either blockade of AT1R or activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). In order to explore how this compound affects the amplitude and kinetics of INa in neurons, a Hodgkin-Huxley-based (HH-based) model designed to mimic effect of Tel on the functional activities of neurons was computationally created in this study. In this framework, the parameter for h inactivation gating variable, which was changed in a stepwise fashion, was implemented to predict changes in membrane potentials (V) as a function of maximal Na⁺ (GNa), K⁺ conductance (GK), or both. As inactivation time course of INa was increased, the bifurcation point of V versus GNa became lower, and the range between subcritical and supercritical values at the bifurcation of V versus GK correspondingly became larger. During a slowing in INa inactivation, the critical boundary between GNa and GK was shifted towards the left. Simulation studies demonstrated that progressive slowing in the inactivation time course of INa resulted in unanticipated increase of neuronal excitability by mimicking the effect of Tel in neuronal cells. Collectively, Tel can directly interact with the NaV channel to increase peak INa as well as to slow INa inactivation. It is thus highly likely that the effects of Tel or its structurally similar drugs could be another intriguing mechanism underlying their pharmacological actions in neurons or neuroendocrine cells occurring in vivo.

Guanine nucleotide induced conformational change of Cdc42 revealed by hydrogen/deuterium exchange mass spectrometry.

Cdc42 regulates pathways related to cell division. Dysregulation of Cdc42 can lead to cancer, cardiovascular diseases and neurodegenerative diseases. GTP induced activation mechanism plays an important role in the activity and biological functions of Cdc42. P-loop, Switch I and Switch II are critical regions modulating the enzymatic activity of Cdc42. We applied amide hydrogen/deuterium exchange coupled with liquid chromatography mass spectrometry (HDXMS) to investigate the dynamic changes of apo-Cdc42 after GDP, GTP and GMP-PCP binding. The natural substrate GTP induced significant decreases of deuteration in P-loop and Switch II, moderate changes of deuteration in Switch I and significant changes of deuteration in the α7 helix, a region far away from the active site. GTP binding induced similar effects on H/D exchange to its non-hydrolysable analog, GMP-PCP. HDXMS results indicate that GTP binding blocked the solvent accessibility in the active site leading to the decrease of H/D exchange rate surrounding the active site, and further triggered a conformational change resulting in the drastic decrease of H/D exchange rate at the remote α7 helix. Comparing the deuteration levels in three activation states of apo-Cdc42, Cdc42-GDP and Cdc42-GMP-PCP, the apo-Cdc42 has the most flexible structure, which can be stabilized by guanine nucleotide binding. The rates of H/D exchange of Cdc42-GDP are between the GMP-PCP-bound and the apo form, but more closely to the GMP-PCP-bound form. Our results show that the activation of Cdc42 is a process of conformational changes involved with P-loop, Switch II and α7 helix for structural stabilization.

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells.

BACKGROUND: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. METHODS: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp techniques. RESULTS: ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50 value of 11.2 µM and enhanced IK(DR) inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. CONCLUSION: Under ART exposure, the inhibitory actions on both IK(DR) and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

Optically active two-dimensional MoS2-based nanohybrids for various biosensing applications: A comprehensive review.

Following the discovery of graphene, there has been a surge in exploring other two-dimensional (2D) nanocrystals, including MoS2. Over the past few decades, MoS2-based nanocrystals have shown great potential applications in biosensing, owing to their excellent physico-chemical properties. Unlike graphene, MoS2 shows layer-dependent finite band gaps (∼1.8 eV for a single layer and ∼1.2 for bulk) and relatively strong interaction with the electromagnetic spectrum. The tunability of the size, shape, and intrinsic properties, such as high optical absorption, electron mobility, mechanical strength and large surface area, of MoS2 nanocrystals, make them excellent alternative probe materials for preparing optical, photothermal, and electrical bio/immunosensors. In this review, we will provide insights into the rapid evolutions in bio/immunosensing applications based on MoS2 and its nanohybrids. We emphasized the various synthesis, characterization, and functionalization routes of 2D MoS2 nanosheets/nanoflakes. Finally, we discussed various fabrication techniques and the critical parameters, including the limit of detection (LOD), linear detection range, and sensitivity of the biosensors. In addition, the role of MoS2 in enhancing the performance of biosensors, the limitations associated with current biosensing technologies, future challenges, and clinical implications are addressed. The advantages/disadvantages of each biosensor technique are also summarized. Collectively, we believe that this review will encourage resolute researchers to follow up further with the state-of-the-art MoS2-based biosensing technology.

Shape and size control of Cu nanoparticles by tailoring the surface morphologies of TiN-coated electrodes for biosensing applications.

A method for controlling the shapes and sizes of Cu nanoparticles during electrodeposition has been developed by tailoring the surface morphologies of TiN-coated electrodes. Larger octahedral Cu NPs grew on a granular TiN film; smaller, irregular Cu NPs formed on a pyramidal TiN film. The surface morphology of the TiN film affected the accumulation of Cu(2+) and hexadecyltrimethylammonium (CTA(+)) ions, leading to the different shapes and sizes of the resulting Cu NPs. The significant steric effect of the CTA(+) ions was confirmed when using the film of pyramidal TiN as the electrode in the CTAB-containing electrolyte; it contributed to the growth of the smaller, irregular Cu NPs. The sensitivity of the smaller, irregular Cu NPs in the detection of glucose was better than that of the larger, octahedral Cu NPs because of the former's greater increase in the Cu(2+)-to-Cu(0) ratio.

A prospective comparison of 3 scoring systems in upper gastrointestinal bleeding.

BACKGROUND: The clinical severities of upper gastrointestinal bleeding (UGIB) are of a wide variety, ranging from insignificant bleeds to fatal outcomes. Several scoring systems have been designed to identify UGIB high- and low-risk patients. The aim of our study was to compare the Glasgow-Blatchford score (GBS) with the preendoscopic Rockall score (PRS) and the complete Rockall score (CRS) in their utilities in predicting clinical outcomes in patients with UGIB. METHODS: We designed a prospective study to compare the performance of the GBS, PRS, and CRS in predicting primary and secondary outcomes in UGIB patients. The primary outcome included the need for blood transfusion, endoscopic therapy, or surgical intervention and was labeled as high risk. The secondary outcomes included rebleeding and 30-day mortality. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values for each system were analyzed. A total of 303 consecutive patients admitted with UGIB during a 1-year period were enrolled. RESULTS: For prediction of high-risk group, AUC was obtained for GBS (0.808), PRS (0.604), and CRS (0.767). For prediction of rebleeding, AUC was obtained for GBS (0.674), PRS (0.602), and CRS (0.621). For prediction of mortality, AUC was obtained for GBS (0.513), PRS (0.703), and CRS (0.620). CONCLUSIONS: In detecting high-risk patients with acute UGIB, GBS may be a useful risk stratification tool. However, none of the 3 score systems has good performance in predicting rebleeding and 30-day mortality because of low AUCs.

Poly(l-Histidine)-Mediated On-Demand Therapeutic Delivery of Roughened Ceria Nanocages for Treatment of Chemical Eye Injury.

Development of topical bioactive formulations capable of overcoming the low bioavailability of conventional eye drops is critically important for efficient management of ocular chemical burns. Herein, a nanomedicine strategy is presented to harness the surface roughness-controlled ceria nanocages (SRCNs) and poly(l-histidine) surface coatings for triggering multiple bioactive roles of intrinsically therapeutic nanocarriers and promoting transport across corneal epithelial barriers as well as achieving on-demand release of dual drugs [acetylcholine chloride (ACh) and SB431542] at the lesion site. Specifically, the high surface roughness helps improve cellular uptake and therapeutic activity of SRCNs while exerting a negligible impact on good ocular biocompatibility of the nanomaterials. Moreover, the high poly(l-histidine) coating amount can endow the SRCNs with an ≈24-fold enhancement in corneal penetration and an effective smart release of ACh and SB431542 in response to endogenous pH changes caused by tissue injury/inflammation. In a rat model of alkali burn, topical single-dose nanoformulation can efficaciously reduce corneal wound areas (19-fold improvement as compared to a marketed eye drops), attenuate ≈93% abnormal blood vessels, and restore corneal transparency to almost normal at 4 days post-administration, suggesting great promise for designing multifunctional metallic nanotherapeutics for ocular pharmacology and tissue regenerative medicine.

Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease.

Dry eye (DE) disease, which is primarily linked to aqueous deficiency, is an escalating health issue worldwide, mainly due to the widespread use of electronic devices. The major obstacles in DE pharmacotherapy include insufficient therapeutic efficacy and low ocular bioavailability. This study presents the development of a ceria-based nanosystem to carry gabapentin (GBT), aiming to offer comprehensive relief from DE symptoms. We prepared multifunctional nanoceria capped with thiolated gelatin followed by cross-linking with glutaraldehyde, yielding a nanocarrier with desirable biocompatibility and antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, and neuronal protective activities. Specifically, the highly abundant thiol groups on gelatin increased the cellular uptake of the nanocarrier by 2.3-fold and its mucin-binding efficiency by 10-fold, thereby extending ocular retention and amplifying therapeutic activity. Moderate cross-linking of the thiolated gelatin not only enhanced the ocular bioavailability of the nanoceria but also provided slow, degradation-controlled release of GBT to promote the lacrimal stimulation to restore the tear film. In a rabbit model of DE, topical administration of our GBT/nanoceria nanoformulation resulted in comprehensive alleviation of symptoms, including repairing corneal epithelial damage, preserving corneal nerve density, and stimulating tear secretion, demonstrating superior performance in comparison to the free drug. These results underscore the safety and potential of this innovative nanoformulation for DE pharmacotherapy.

Highly Retina-Permeating and Long-Acting Resveratrol/Metformin Nanotherapeutics for Enhanced Treatment of Macular Degeneration.

The development of therapeutics for effective treatments of retinal diseases is significantly constrained by various biological barriers. We herein report a nanomedicine strategy to develop nanotherapeutics featured with not only high retinal permeability but also sustained bioactive delivery. Specifically, the nanotherapeutics are rationally designed via aminolysis of resveratrol-encapsulated polycaprolactone nanoparticles (R@PCL NPs), followed by the formation of amide linkages with carboxyl-terminated transacting activator of transcription cell penetrating peptide (T) and metformin (M). The R@PCL-T/M NP nanotherapeutics are demonstrated in vitro to possess persistent drug release profiles, good ocular biocompatibility, and potent bioactive activities for targeting prevailing risk factors associated with retinal diseases. In vivo studies indicate that single-dose intravitreal administration of the R@PCL-T/M NPs can effectively improve retinal permeability (∼15-fold increase), prevent loss of endogenous antioxidants, and suppress the growth of abnormal vessels in the retina with macular degeneration for 56 days. This high treatment efficacy can be ascribed to the enhanced retinal permeability of the nanotherapeutics in conjunction with the sustained pharmacological activity of the dual drugs (R and M) in the retinal pigment epithelial region. These findings show a great promise for the development of pharmacological nanoformulations capable of targeting the retina and thereby treating complex posterior segment diseases with improved efficacies.

Critical slowing down near a magnetic quantum phase transition with fermionic breakdown.

When a system close to a continuous phase transition is subjected to perturbations, it takes an exceptionally long time to return to equilibrium. This critical slowing down is observed universally in the dynamics of bosonic excitations, such as order-parameter collective modes, but it is not generally expected to occur for fermionic excitations. Here using terahertz time-domain spectroscopy, we find evidence for fermionic critical slowing down in YbRh2Si2 close to a quantum phase transition between an antiferromagnetic phase and a heavy Fermi liquid. In the latter phase, the relevant quasiparticles are a quantum superposition of itinerant and localized electronic states with a strongly enhanced effective mass. As the temperature is lowered on the heavy-Fermi-liquid side of the transition, the heavy-fermion spectral weight builds up until the Kondo temperature TK ≈ 25 K, then decays towards the quantum phase transition and is, thereafter, followed by a logarithmic rise of the quasiparticle excitation rate below 10 K. A two-band heavy-Fermi-liquid theory shows that this is indicative of the fermionic critical slowing down associated with heavy-fermion breakdown near the quantum phase transition. The critical exponent of this breakdown could be used to classify this system among a wider family of fermionic quantum phase transitions that is yet to be fully explored.

Traveler's knowledge, attitude, and practice about travel health insurance: A community-based questionnaire study.

BACKGROUND: Travel, especially international travel, has become one of the most popular leisure activities in the world. The risk of accidents and travel-related illnesses, including infectious and non-communicable diseases, should not be neglected. To provide a more comprehensive pre-travel consultation to international travelers, this study aimed to investigate the knowledge, attitude, and practice of travelers about travel health insurance. METHODS: This was a cross-sectional study. Anonymous structured questionnaires were distributed to 1000 visitors to the Taiwan International Travel Fair in May 2019. RESULTS: The top three important travel health insurances were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%), and 24-hour emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel health insurances and the willingness of pre-travel consultation. CONCLUSIONS: Most travelers would buy travel health insurance; however, disproportional respondents understood the content of travel health insurance. Most travelers considered travel clinics to be the most reliable information source regarding travel health insurance. Therefore, travel medicine specialists are encouraged to offer more information about travel health insurance during pre-travel consultation.

Is direct transport to a trauma centre best for patients with severe traumatic brain injury? A study in south-central Taiwan.

OBJECTIVE: This study attempted to identify any differences between the outcomes of patients with severe traumatic brain injury (TBI) who were directly transported to Chang Gung Memorial Hospital and those who were stabilised initially at other hospitals in south-central Taiwan. METHODS: A retrospective review of the records of 254 patients with isolated severe TBI who visited this hospital's emergency department from July 2003 to June 2008, of whom 167 were referred from other hospitals. Logistic regression was used to assess the effects of transfer and its components on mortality. RESULTS: Transfer from another hospital was not significantly correlated with mortality in this study (OR 0.513, 95% CI 0.240 to 1.097). Moreover, neither intubation (OR 1.356, 95% CI 0.445 to 4.133) nor transfer time over 4 h (OR 0.549, 95% CI 0.119 to 1.744) had a significant effect on mortality. CONCLUSION: No differences in outcome were found between patients with isolated severe TBI who were directly transported and those transferred to this hospital's emergency room.

Pretravel preparation and factors associated with willingness to seek pretravel consultation among Taiwanese travelers.

BACKGROUND: Although globalization promotes economic development, cross-border infectious disease transmission is still a serious threat to health. Taiwan is geographically close to Southeast and South Asia, but the needs and expectations of Taiwanese travelers with regard to travel medicine are still largely unknown. This study aimed to clarify the pretravel preparations, needs, willingness to seek pretravel consultation, and factors associated with willingness, in order to provide valuable information for improvement of healthcare service. METHODS: Data were collected with anonymous structured questionnaires distributed to 477 visitors who tried to get travel health information from New Southbound Health Center between June and November 2019. A multivariate stepwise logistic regression analysis was applied to identify factors associated with the visitors' willingness to seek pretravel consultation. RESULTS: A total of 304 questionnaires (64%) were collected. Eighty-three percent of the respondents were willing to seek pretravel consultation. A higher level of education (odds ratio 3.6 [95% CI 1.58-8.22]), having a plan to obtain travel medical insurance (2.5 [1.18-5.28]), concern with gastrointestinal diseases (2.0 [1.04-3.94]), concern with mosquito-borne diseases (2.0 [2.07-3.95]), and concern with noncommunicable diseases (2.2 [1.02-4.96]) were independent factors associated with willingness to seek pretravel consultation.: CONCLUSIONS: We found that most of the travelers were willing to seek pretravel consultation. Our study highlighted the need to enhance awareness about travel-related illness among these travelers. Strategies should be tailored according to these findings to help prevent epidemics and improve healthcare service in the future.

The association between anemia and the mortality of severe traumatic brain injury in emergency department.

BACKGROUND: Anemia is a common medical problem for critically ill patients. Blood transfusion to augment oxygen delivery for these patients has been a traditional therapy. However, few studies have identified the impact of anemia on individuals suffering from severe traumatic brain injury (TBI). Hence, this study aims to evaluate the effects of initial anemia on patients with severe TBI admitted to the Emergency Unit. METHODS: We reviewed the medical records of patients with isolated severe TBI admitted to the Emergency Unit of a university hospital from July 2003 to June 2008. Patients were divided into two groups based on their initial anemia data taken while in the Emergency Unit. The anemia datum is defined as hemoglobin (Hb) <10 mg/dL. The t test was used to identify the differences between the two groups, while logistic regression was applied to determine any significant differences found in the statistical analysis. RESULTS: A total of 234 patients were signed up in our study. Based on their initial hemoglobin at emergency department, 23 patients (9.8%) comprised the anemia group, 17 patients (7.3%) comprised the nonanemia group, whereas 112 patients (47.9%) belonging to the nonanemia group were deceased. There is no significant difference between the two groups (p = 0.076; odds ratio, 0.97; confidence interval, 0.78-1.05). CONCLUSION: This study shows that initial anemia is not a mortality risk factor for patients with isolated severe blunt TBI.

Field Sanitation and Foliar Application of Streptomyces padanus PMS-702 for the Control of Rice Sheath Blight.

Rice sheath blight (ShB), caused by Rhizoctonia solani Kühn AG1-IA, is one of the destructive rice diseases worldwide. The aims of this study were to develop biocontrol strategies focusing on field sanitation and foliar application with a biocontrol agent for ShB management. Streptomyces padanus PMS-702 showed a great antagonistic activity against R. solani. Fungichromin produced by S. padanus PMS-702, at 3.07 mg/l inhibited 50% mycelial growth, caused leakage of cytoplasm, and inhibited the formation of infection structures of R. solani. Fungichromin could reach to 802 mg/l when S. padanus PMS-702 was cultured in MACC broth for 6 days. Addition of 0.5% S. padanus PMS-702 broth into soil decreased the survival rate of the pathogen compared to the control. Soil amended with 0.5% S. padanus broth and 0.5% tea seed pomace resulted in the death of R. solani mycelia in the infested rice straws, and the germination of sclerotia was inhibited 21 days after treatment. Greenhouse trials revealed that S. padanus cultured in soybean meal-glucose (SMGC-2) medium after mixing with different surfactants could enhance its efficacy for inhibiting the pathogen. Of six surfactants tested, the addition of 2% tea saponin was the most effective in suppressing the pathogen. S. padanus broth after being fermented in SMGC-2, mixed with 2% tea saponin, diluted 100 fold, and sprayed onto rice plants significantly reduced ShB disease severity. Thus, S. padanus PMS-702 is an effective biocontrol agent. The efficacy of S. padanus PMS-702 for disease control could be improved through formulation.

Using Deep Neural Networks for Predicting Age and Sex in Healthy Adult Chest Radiographs.

BACKGROUND: The performance of chest radiography-based age and sex prediction has not been well validated. We used a deep learning model to predict the age and sex of healthy adults based on chest radiographs (CXRs). METHODS: In this retrospective study, 66,643 CXRs of 47,060 healthy adults were used for model training and testing. In total, 47,060 individuals (mean age ± standard deviation, 38.7 ± 11.9 years; 22,144 males) were included. By using chronological ages as references, mean absolute error (MAE), root mean square error (RMSE), and Pearson's correlation coefficient were used to assess the model performance. Summarized class activation maps were used to highlight the activated anatomical regions. The area under the curve (AUC) was used to examine the validity for sex prediction. RESULTS: When model predictions were compared with the chronological ages, the MAE was 2.1 years, RMSE was 2.8 years, and Pearson's correlation coefficient was 0.97 (p < 0.001). Cervical, thoracic spines, first ribs, aortic arch, heart, rib cage, and soft tissue of thorax and flank seemed to be the most crucial activated regions in the age prediction model. The sex prediction model demonstrated an AUC of >0.99. CONCLUSION: Deep learning can accurately estimate age and sex based on CXRs.

Gene ontology concept recognition using named concept: understanding the various presentations of the gene functions in biomedical literature.

OBJECTIVE: A major challenge in precision medicine is the development of patient-specific genetic biomarkers or drug targets. The firsthand information of the genes associated with the pathologic pathways of interest is buried in the ocean of biomedical literature. Gene ontology concept recognition (GOCR) is a biomedical natural language processing task used to extract and normalize the mentions of gene ontology (GO), the controlled vocabulary for gene functions across many species, from biomedical text. The previous GOCR systems, using either rule-based or machine-learning methods, treated GO concepts as separate terms and did not have an efficient way of sharing the common synonyms among the concepts. MATERIALS AND METHODS: We used the CRAFT corpus in this study. Targeting the compositional structure of the GO, we introduced named concept, the basic conceptual unit which has a conserved name and is used in other complex concepts. Using the named concepts, we separated the GOCR task into dictionary-matching and machine-learning steps. By harvesting the surface names used in the training data, we wildly boosted the synonyms of GO concepts via the connection of the named concepts and then enhanced the capability to recognize more GO concepts in the text. The source code is available athttps://github.com/jeroyang/ncgocr. RESULTS: Named concept gene ontology concept recognizer (NCGOCR) achieved 0.804 precision and 0.715 recall by correct recognition of the non-standard mentions of the GO concepts. DISCUSSION: The lack of consensus on GO naming causes diversity in the GO mentions in biomedical manuscripts. The high performance is owed to the stability of the composing GO concepts and the lack of variance in the spelling of named concepts. CONCLUSION: NCGOCR reduced the arduous work of GO annotation and amended the process of searching for the biomarkers or drug targets, leading to improved biomarker development and greater success in precision medicine.

The comprehensive electrophysiological study of curcuminoids on delayed-rectifier K+ currents in insulin-secreting cells.

Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic ß-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of IK(DR) in INS-1 cells was 1.26µM. Despite the inability of CUR to alter the activation rate of IK(DR), it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of IK(DR) to hyperpolarized potential and slowed the recovery of IK(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on IK(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na+ current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of IK(DR) and the increase of current inactivation also occurred in ßTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect.