Miracle-dz/UniFAR-FTUs huggingface dataset:
Purification, Characterization and Degradation Performance of a Novel Dextranase from Penicillium cyclopium CICC-4022

A novel dextranase was purified from Penicillium cyclopium CICC-4022 by ammonium sulfate fractional precipitation and gel filtration chromatography. The effects of temperature, pH and some metal ions and chemicals on dextranase activity were investigated. Subsequently, the dextranase was used to produce dextran with specific molecular mass. Weight-average molecular mass (Mw) and the ratio of weight-average molecular mass/number-average molecular mass, or polydispersity index (Mw/Mn), of dextran were measured by multiple-angle laser light scattering (MALS) combined with gel permeation chromatography (GPC). The dextranase was purified to 16.09-fold concentration; the recovery rate was 29.17%; and the specific activity reached 350.29 U/mg. Mw of the dextranase was 66 kDa, which is similar to dextranase obtained from other Penicillium species reported previously. The highest activity was observed at 55 °C and a pH of 5.0. This dextranase was identified as an endodextranase, which specifically degraded the α-1,6 glucosidic bonds of dextran. According to metal ion dependency tests, Li+, Na+ and Fe2+ were observed to effectively improve the enzymatic activity. In particular, Li+ could improve the activity to 116.28%. Furthermore, the dextranase was efficient at degrading dextran and the degradation rate can be well controlled by the dextranase activity, substrate concentration and reaction time. Thus, our results demonstrate the high potential of this dextranase from Penicillium cyclopium CICC-4022 as an efficient enzyme to produce specific clinical dextrans.
Effect of blackberry juice (Rubus fruticosus L.) on anxiety-like behaviour in Wistar rats

Abstract The present study evaluated the effects of blackberry juice that is rich in different concentrations of anthocyanins and polyphenols (2.6 mg/kg anthocyanins, 14.57 mg/kg polyphenols; 5.83 mg/kg anthocyanins, 27.10 mg/kg polyphenols; 10.57 mg/kg anthocyanins, 38.40 mg/kg polyphenols) on anxiety-like behaviour in Wistar rats. The rats were treated with blackberry juice for 21 days and then tested in the elevated plus maze, locomotor activity test and forced swim test. The results were compared with a reference anxiolytic drug diazepam (2.0 mg/kg) and vehicle (8.7 ml/kg). The intermediate dose of blackberry juice exerted an anxiolytic-like effect that was similar to diazepam, without affecting locomotive activity. The low and high doses of blackberry juice exerted no significant effects on anxiety-like behaviour compared with vehicle. In the forced swim test, both the high and intermediate doses of blackberry juice reduced total immobility time, suggesting a protective effect against behavioural changes that are induced by acute stress. These findings suggest a potential therapeutic effect of blackberry juice on anxiety that is associated with a stressful event. Graphical Abstract
Neurocognitive SuperAging in Older Adults Living With HIV: Demographic, Neuromedical and Everyday Functioning Correlates

Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
The effect of age on in-vivo spine stiffness, postures and discomfort responses during prolonged sitting exposures

Abstract Many industrialised working populations are ageing and prolonged sitting exposures are prevalent across occupational sectors. The purpose of this work was to determine the effect of age and sex on passive spine stiffness, postures and discomfort in response to seated work. A total of 34 participants were recruited, with 17 older adults with an average age of (standard deviation) 63.7 (±3.9) years and 17 younger adults aged 23.8 (±5.0) years. Participants were asked to sit continuously for 90 min while typing. Baseline passive spine stiffness was higher in older adults at 40% flexion compared to younger adults (p = .0233). Older adults sat in less normalised flexion, at 33.4% (±16.4) compared to 60.9% (±20.2) in the younger group (p = .0003). Discomfort was higher among older adults in the neck, right shoulder and middle back regions (p < .0086). An understanding of age-specific responses to workplace exposures is essential to determine whether age-specific interventions are warranted. Practitioner summary: Older adults had higher passive spine stiffness and sat with less flexion during prolonged sitting. Discomfort was higher among older adults and occurred earlier in the simulation compared to younger participants, indicating that interventions, such as walking breaks may need to be implemented earlier during sitting for aged workers.
In vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies.

OBJECTIVES To investigate the in vitro activity of olorofim (F901318), a novel broad-spectrum antifungal agent, against 150 strains belonging to 16 different cryptic species of Aspergillus by EUCAST and CLSI methodologies. METHODS Olorofim, amphotericin B, micafungin, posaconazole and voriconazole were tested against cryptic species belonging to Aspergillus fumigatus complex (n = 57), Aspergillus ustus complex (n = 25), Aspergillus niger complex (n = 20), Aspergillus flavus complex (n = 20), Aspergillus circumdati complex (n = 15) and Aspergillus terreus complex (n = 13) using EUCAST and CLSI methodologies for broth microdilution susceptibility testing of antifungal agents. RESULTS Olorofim was the only drug with activity against all cryptic species of Aspergillus tested, including the multiresistant species Aspergillus lentulus, Aspergillus fumigatiaffinis and Aspergillus calidoustus. Geometric means of MICs for olorofim were lower (0.017, 0.015 and 0.098 mg/L, respectively, for EUCAST; and 0.015, 0.015 and 0.048 mg/L, respectively, for CLSI) than for amphotericin B (4.438, 12.699 and 0.554 mg/L, respectively, for EUCAST; and 0.758, 1.320 and 0.447 mg/L, respectively, for CLSI), voriconazole (2.549, 2.297 and 5.856 mg/L, respectively, for EUCAST; and 2.071, 1.741 and 5.657 mg/L, respectively, for CLSI) and posaconazole (0.307, 0.308 and 12.996 mg/L, respectively, for EUCAST; and 0.391, 0.215 and 9.514 mg/L, respectively, for CLSI). CONCLUSIONS Olorofim shows encouraging in vitro activity against cryptic species of Aspergillus that can be hard to treat with current antifungal therapies. Further studies are warranted in order to assess its efficacy.
Design of a light-gated proton channel based on the crystal structure of Coccomyxa rhodopsin

Structural analysis enables conversion of an Arctic algal light-driven ion pump into a light-gated ion channel. The light between pumps and channels Whereas pumps move ions actively, channels move ions passively. Fudim et al. generated a high-resolution crystal structure for Coccomyxa subellipsoidea rhodopsin, a light-activated proton pump. These data enabled the authors to identify a critical interaction between Arg83 and Tyr14 in a transmembrane domain and generate a point mutant of this rhodopsin that behaved as a light-gated proton channel. These results provide greater insight into the molecular determinants that distinguish proton pumps from channels. The light-driven proton pump Coccomyxa subellipsoidea rhodopsin (CsR) provides—because of its high expression in heterologous host cells—an opportunity to study active proton transport under controlled electrochemical conditions. In this study, solving crystal structure of CsR at 2.0-Å resolution enabled us to identify distinct features of the membrane protein that determine ion transport directivity and voltage sensitivity. A specific hydrogen bond between the highly conserved Arg83 and the nearby nonconserved tyrosine (Tyr14) guided our structure-based transformation of CsR into an operational light-gated proton channel (CySeR) that could potentially be used in optogenetic assays. Time-resolved electrophysiological and spectroscopic measurements distinguished pump currents from channel currents in a single protein and emphasized the necessity of Arg83 mobility in CsR as a dynamic extracellular barrier to prevent passive conductance. Our findings reveal that molecular constraints that distinguish pump from channel currents are structurally more confined than was generally expected. This knowledge might enable the structure-based design of novel optogenetic tools, which derive from microbial pumps and are therefore ion specific.
Use of ion mobility mass spectrometry to enhance cumulative analytical specificity and separation to profile 6-C/8-C-glycosylflavone critical isomer pairs and known-unknowns in medicinal plants.

INTRODUCTION Plant medicine/herbal extracts are typically complex, encompassing a wide range of flavonoid diversity and biological benefits. Combined with a lack of standards; species authentication profiling is a challenge. A non-targeted screening strategy using two-dimensional (2D) separation and specificity of ultra-high-performance liquid chromatography ion mobility collision-induced dissociation mass spectrometry (UHPLC-IM-CID-MS) has been investigated, to identify the 6-C and 8-C-glycosylflavone isomer orientin/isoorientin and vitexin/isovitexin pairs in Passiflora species. Utilising available standards and "known-unknowns" a reference CCS (collision cross-section) speciation finger print for Passiflora extracts could be generated to illustrate species profiling. MATERIAL AND METHODS SPE was performed to extract flavonoids of interest from powdered and ground Passiflora leaf. Chromatographic separation was achieved via UHPLC and analysis performed using positive/negative ion electrospray coupled with linear T-wave IM-MS (calibrated to perform accurate mass and CCS measurements). RESULTS Comparative phytochemical screening of Passiflora alata, P. edulis, P. incarnata and P. caerulea leaf extracts has generated CCS, CID IM product ion spectra, 2D separation with UHPLC-IM-MS, enabling the unequivocal identification of flavone C-glycosides in complex extracts. A phytochemical reference CCS library was generated comprised of "knowns" and "known-unknowns". Isomers have been differentiated using a CCS metric enabling novel CCS specific isomeric quantitation of co-eluting isomers. CONCLUSIONS The screening approach illustrated has the potential to play an important role in the profiling of medicinal plants to determine phytochemical make-up and improve consumer safety through generation of highly specific speciation profiles.
Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Siltuximab in High-Risk Smoldering Multiple Myeloma

Purpose: IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma. Patients and Methods: In a randomized, double-blind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety. Results: Median age was 62 years (range: 21–84); 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24–1.04); P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3; the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group). Conclusions: Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.
Structure of Vibrio FliL, a New Stomatin-like Protein That Assists the Bacterial Flagellar Motor Function

Some flagellated bacteria regulate motor torque in response to the external load change. This behavior is critical for survival, but the mechanism has remained unknown. Here, we focused on a key protein, FliL of Vibrio alginolyticus, and solved the crystal structure of its periplasmic region (FliLPeri). FliLPeri reveals striking structural similarity to a conserved domain of stomatin, which is involved in ion channel regulation in some organisms, including mammals. FliLPeri forms a ring with an inner diameter that is comparable in size to the stator unit. The mutational analyses suggested that the presence of the ring-like assembly of FliL around the stator unit enhances the surface swarming of Vibrio cells. Our study data also imply that the structural element for the ion channel regulation is conserved from bacteria to mammals. ABSTRACT Many motile bacteria swim or swarm using a filamentous rotating organelle, the flagellum. FliL, a component protein of the flagellar motor, is known to enhance the motor performance under high-load conditions in some bacteria. Here we determined the structure of the periplasmic region of FliL (FliLPeri) of the polar flagellum of Vibrio alginolyticus. FliLPeri shows a remarkable structural similarity to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain of stomatin family proteins, some of which are involved in modulation of ion channel activities in various organisms. FliLPeri forms a ring assembly in the crystal with an inner diameter of around 8 nm, which is comparable to the size of the stator unit. Mutational analyses suggest that the FliL ring forms a complex with the stator unit and that the length of the periplasmic linkers of FliL and the stator B-subunit is essential for the complex formation. We propose a model of the FliL-stator complex to discuss how Vibrio FliL modulates stator function in the bacterial flagellar motor under conditions of high viscosity. IMPORTANCE Some flagellated bacteria regulate motor torque in response to the external load change. This behavior is critical for survival, but the mechanism has remained unknown. Here, we focused on a key protein, FliL of Vibrio alginolyticus, and solved the crystal structure of its periplasmic region (FliLPeri). FliLPeri reveals striking structural similarity to a conserved domain of stomatin, which is involved in ion channel regulation in some organisms, including mammals. FliLPeri forms a ring with an inner diameter that is comparable in size to the stator unit. The mutational analyses suggested that the presence of the ring-like assembly of FliL around the stator unit enhances the surface swarming of Vibrio cells. Our study data also imply that the structural element for the ion channel regulation is conserved from bacteria to mammals.
External Stimuli Predict Financial Market Behavior From the Brain Perception Perspective

The information that the brain perceives is usually consistent with a range of possible incentives. Therefore, all of our perceptual decisions are almost made in an uncertain situation. As we all know, this uncertainty affects our behavior, but how this uncertainty to modify human behavior is unclear. We attempt to establish the relationship between financial market behavior and external stimulus information. We adopt a new approach that is entirely different from the existing literature. This approach combines neuroscience and machine learning methods to explore how the brain perceives external stimulus information and ultimately influences financial market behavior. We improve the BP neural network in two aspects. Firstly, the output of the brain perception model serves as the input of the BP neural network. By this method, the number of input nodes of the BP neural network can be reduced to six, and the mental process behind the stimulus is simulated. Secondly, we optimize the parameters of the brain perception model and construct the optimal brain perception model for specific external stimuli. By comparing the performance of all models, the results show that the improved BP neural network is superior to other models. Firstly, in all two periods, trends are similar between the improved BP neural network and other models. Secondly, in all three samples, except for one result, the average prediction performance of the improved BP neural network is better than other models.
Surprise-related activation in the nucleus accumbens interacts with music-induced pleasantness

Abstract How can music—merely a stream of sounds—be enjoyable for so many people? Recent accounts of this phenomenon are inspired by predictive coding models, hypothesizing that both confirmation and violations of musical expectations associate with the hedonic response to music via recruitment of the mesolimbic system and its connections with the auditory cortex. Here we provide support for this model, by revealing associations of music-induced pleasantness with musical surprises in the activity and connectivity patterns of the nucleus accumbens (NAcc)—a central component of the mesolimbic system. We examined neurobehavioral responses to surprises in three naturalistic musical pieces using fMRI and subjective ratings of valence and arousal. Surprises were associated with changes in reported valence and arousal, as well as with enhanced activations in the auditory cortex, insula and ventral striatum, relative to unsurprising events. Importantly, we found that surprise-related activation in the NAcc was more pronounced among individuals who experienced greater music-induced pleasantness. These participants also exhibited stronger surprise-related NAcc–auditory cortex connectivity during the most pleasant piece, relative to participants who found the music less pleasant. These findings provide a novel demonstration of a direct link between musical surprises, NAcc activation and music-induced pleasantness.
In Situ Quantification of the Young’s Modulus of Nuclei in Multiple Cellular States Using a Modified Fiber Probe Sensor

In this paper, a modified fiber probe sensor (MFP sensor) with a considerable length–diameter ratio tip was developed to quantitatively characterize the Young’s modulus of the cell nucleus in multiple cellular states. The MFP sensor has a needle tip with an extended length of $30~\mu \text{m}$ and a diameter of 150 nm. The length of the tip exceeds the diameter of most cells so that it can penetrate the cell membrane with minimal damage and reach the nucleus. This allows the measurement of the Young’s modulus of intact cell nuclei under different cellular states without the phenomenon that the cantilever contacts the cell membrane. Moreover, the stiffness of the MFP sensor is reduced by a factor of 25 to better match that of the cell membrane and nucleus, which enables high-precision mechanical measurements. The MFP sensor was successfully used to quantify the Young’s modulus of the intact cell nuclei in the non-adherent, adherent, and early apoptotic states. Experimental results validated the capability and the versatility of the developed method.
Effects of a brain tumor in a dispersive human head on SAR and temperature rise distributions due to RF sources at 4G and 5G frequencies

ABSTRACT In this paper, effects of a brain tumor located in a dispersive human head model on specific absorption rate (SAR) and temperature rise distributions due to different types of RF sources at 4G and 5G cellular frequencies are investigated with the use of a multiphysics model. This multiphysics model analyzes the dispersive human head with the brain tumor and provides the SAR and temperature rise distributions in the head due to the RF source operated at 4G and 5G cellular frequencies in a single finite-difference time-domain simulation. An adjacent antenna operated at 4G and 5G cellular frequencies to the human head is considered as the RF source for near-field exposure, while a plane wave field radiated by base stations operated at 4G and 5G cellular frequencies is considered as the RF source for far-field exposure. Numerical results show that the brain tumor in the head slightly affects the SAR and temperature rise distributions due to different RF sources at 4G and 5G cellular frequencies.