Preparation of multicore millimeter-sized spherical alginate capsules to specifically and sustainedly release fish oil

Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.

Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.

A Preliminary Study on a Specifically Expressed Arabidopsis Promoter in Vascular Bundle

From a population of about 3500 single plants in Arabidopsis promoter trapping bank, one plant whose GUS-gene had been specifically expressed in vascular bundle, was screened by the method of gus tissue staining. The T-DNA flanking sequence was amplified using TAIL-PCR. This band will be purified and connected to TA cloning vector. After sequencing and searching in the genebank, its function will be demonatrated through transformation.

Effect of specifically-adsorbed polysulfides on the electron transfer kinetics of sodium metal anodes

Room-temperature sodium-sulfur(RT Na-S)batteries hold great promise for large-scale energy storage applications owing to the high energy density and earth-abundance of Na and S.However,the dissolution and migration of sodium polysulfides,uncontrollable Na dendrite growth,and the lack of studies on Na electrodeposition kinetics have hindered the development of these batteries.Herein,we reveal the mechanism of sodium polysulfides on the Na plating/stripping kinetics using a three-electrode system.First,the kinetic behavior deviates from the commonly supposed Butler-Volmer model,which is well described by the Marcus model.In addition,the specific adsorption of polysulfides on the sodium electrode surface is a key factor influencing the kinetics.Higher-order polysulfides(S_(8)^(2-)and S_(6)^(2-))exhibit distinct specific adsorption behaviors because of their high adsorption energies compared to lower-order polysulfides(S_(4)^(2-)and S_(2)^(2-)).The electrostatic effect caused by specific adsorption can accelerate the kinetics,whereas the blocking effect can slow the kinetics.Thus,this competitive relationship enables low concentrations of high-order polysulfides to stimulate kinetics.This implies that a weak shuttle effect is beneficial for obtaining a stable Na deposition in RT Na-S batteries.An in-depth understanding of the Na electrodeposition kinetics provides beneficial clues for future metal sodium/electrolyte interface designs.

Identifying peptides that specifically bind to MDA-MB-468 breast cancer cells

Objective To use phage display technique to screen for small polypeptides that specifically bind to MDA-MB-468 cells.Methods A random heptapeptide phage display library was used for in vitro screening against target MDA-MB-468 cells.SC1180 cells were used for subtractive selection.High-affinity phage DNA was extracted,and peptides were sequenced.Results(1)The original library capacity of the polypeptide library was 2×10^13 pfu/mL,and phage titer was determined over 4 rounds.The average library capacity was 1.8×10^13 pfu/mL.(2)Subtractive screening showed that the phage library volume of each round was 1.8×10^12 pfu/mL,and that there was an enrichment effect in each subsequent round.Screening was stopped after the fourth round.(3)PCR results showed that the size of 39 products(78.0%)and 11 products(22%),were 300 bp and 258 bp,respectively.Thirty positive phages were selected for DNA extraction and sequencing,and the corresponding amino acid sequence was LMTRXSK.The sequence had no homology with known genes or proteins.Conclusion Using the phage display technique,we identified that the short polypeptide,LMTRXSK,specifically binds MDA-MB-468 human breast cancer cells.

Estimating Biological Age with DNA Methylation Clocks

Recently,a research team led by researchers from the Beijing Institute of Genomics and Institute of Zoology,both under the Chinese Academy of Sciences,and their collaborators from the Quzhou Affiliated Hospital of Wenzhou Medical University developed innovative epigenetic clocks specifically for Chinese populations,offering a more tailored approach to measuring biological age among Chinese population(doi:10.1093/procel/pwae011).

Durable K-ion batteries with 100% capacity retention up to 40,000 cycles

Currently,the major challenge in terms of research on K-ion batteries is to ensure that they possess satisfactory cycle stability and specific capacity,especially in terms of the intrinsically sluggish kinetics induced by the large radius of K+ions.Here,we explore high-performance K-ion half/full batteries with high rate capability,high specific capacity,and extremely durable cycle stability based on carbon nanosheets with tailored N dopants,which can alleviate the change of volume,increase electronic conductivity,and enhance the K+ion adsorption.The as-assembled K-ion half-batteries show an excellent rate capability of 468 mA h g^(−1) at 100 mA g^(−1),which is superior to those of most carbon materials reported to date.Moreover,the as-assembled half-cells have an outstanding life span,running 40,000 cycles over 8 months with a specific capacity retention of 100%at a high current density of 2000 mA g^(−1),and the target full cells deliver a high reversible specific capacity of 146 mA h g^(−1) after 2000 cycles over 2 months,with a specific capacity retention of 113%at a high current density of 500 mA g^(−1),both of which are state of the art in the field of K-ion batteries.This study might provide some insights into and potential avenues for exploration of advanced K-ion batteries with durable stability for practical applications.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Enzyme-Triggered Fluorescence Turn-on： A Probe for Specifically Imaging Ovarian-Cancer-Related γ-Glutamyltranspeptidase

A fluorescent turn-on probe for specifically targeting γ-glutamyltranspeptidase （GGT） was designed and synthe- sized by integrating boron-dipyrromethene （BODIPY） as a chromophore and glutathione （GSH） as the GGT sub- strate. GGT-catalyzed the cleavage of the γ-glutamyl bond and generated the aromatic hydrocarbon transfer between the sulfur and the nitrogen atom in BODIPY, leading to distinct optical changes. Such specific responsiveness pro- vides an easily distinguishable fluorescence signal to visualize the GGT activity in living cells and differentiate GGT-positive cancer cells from GGT-negative cells.

A novel saliva-based miRNA profile to diagnose and predict oral cancer

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

Magnetic and electrical transport properties in GdAlSi and SmAlGe

We conduct a detailed examination of the magnetic and electrical transport properties in GdAlSi and SmAlGe crystals,which possess a LaPtSi-type structure(space group I4_(1)md).The magnetic susceptibility data unambiguously reveal magnetic ordering below a characteristic transition temperature(T_(N)).For GdAlSi,a hysteresis loop is observed in the magnetization and magnetoresistance curves within the ab plane when the magnetic field is applied below T_(N),which is around32 K.Notable specific heat anomalies are detected at 32 K for GdAlSi and 6 K for SmAlGe,confirming the occurrence of magnetic transitions.In addition,the extracted magnetic entropy at high temperatures is consistent with the theoretical value of Rln(2J+1) for J=7/2 in Gd^(3+) and J=5/2 in Sm^(3+),respectively.SmAlGe also exhibits Schottky-like specific heat contributions.Additionally,both GdAlSi and SmAlGe exhibit positive magnetoresistance and a normal Hall effect.

Review of the SiC LDMOS power device

Silicon carbide(SiC),as a third-generation semiconductor material,possesses exceptional material properties that significantly enhance the performance of power devices.The SiC lateral double-diffused metal–oxide–semiconductor(LDMOS)power devices have undergone continuous optimization,resulting in an increase in breakdown voltage(BV)and ultra-low specific on-resistance(Ron,sp).This paper has summarized the structural optimizations and experimental progress of SiC LDMOS power devices,including the trench-gate technology,reduced surface field(RESURF)technology,doping technology,junction termination techniques and so on.The paper is aimed at enhancing the understanding of the operational mechanisms and providing guidelines for the further development of SiC LDMOS power devices.

Gamma oscillations and their role in orchestrating balance and communication following stroke

Induced brain oscillations in the gamma range have recently garnered attention due to their reported neuroprotective effects in the treatment of Alzheimer’s disease.This method differs from pharmacological approaches by tapping into the neuronal population dynamics that underlie the homeostatic processes in the brain that are crucial for the recovery of function.Recently,induced gamma-range oscillations have been used to improve cerebral blood flow,motor function,and synaptic plasticity in a mouse model of focal stroke,highlighting the broad potential of recruiting intrinsic recovery processes for the treatment of neurological conditions.Addressing open questions,such as the frequency specificity of the benefits,will shed light on the intrinsic processes involved and allow clinicians to optimize recovery after stroke.

Linear magnetoresistance and structural distortion in layered SrCu_(4-x)P_(2) single crystals

We report a systematic study on layered metal SrCu_(4-x)P_(2) single crystals via transport, magnetization, thermodynamic measurements and structural characterization. We find that the crystals show large linear magnetoresistance without any sign of saturation with a magnetic field up to 30T. We also observe a phase transition with significant anomalies in resistivity and heat capacity at T_(p)~140 K. Thermal expansion measurement reveals a subtle lattice parameter variation near Tp, i.e.,?L_(c)/L_(c)~0.062%. The structural characterization confines that there is no structure transition below and above T_(p). All these results suggest that the nonmagnetic transition of SrCu_(4-x)P_(2) could be associated with structural distortion.

Accurate diagnosis of severe coronary stenosis based on resting magnetocardiography: a prospective, single-center, cross-sectional analysis

OBJECTIVE To evalu ate the role of resting magnetocardiography in identifying seve re coronary artery stenosis in patients with suspected coronary artery disease.METHODS A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography:the non-severe coronary stenusis group(<70% stenosis) and the severe coronary stenosis group(≥70% stenosis).The diagnostic model was constructed using magnetic field map(MFM) parameters,either individually or in combination with clinical indicators.The performance of the models was evaluated using receiver operating characteristic curves,accuracy,sensitivity,specificity,positive predictive value(PPV) and ne gative predictive value(NPV).Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models,respectively.RESULTS In the severe coronary stenosis group,QR_MCTDd,S_MDp,and TT_(MA)C_(50) were significantly higher than those in the non-severe coronary stenosis group(10,46±10.66 vs,5.11±6.07,P <0.001;7.2±8.64 vs.4.68±6.95,P=0.003;0.32±57.29 vs.0.26±57.29,P <0.001).While,QR_MV_(amp),R_(MA),and T_(MA) in the severe coronary stenosis group were lower(0.23±0.16 vs.0.28±0.16,P<0.001;55.06±48.68 vs.59.24±53.01,P<0.001;51.67±39.32 vs. 60.45±51.33,P <0.001).Seven MFM parameters were integrated into the model,resulting in an area under the curve of 0.810(95% CI:0.765-0.855).The sensitivity,specificity,PPV,NPV,and accurecy were 71.7%,80.4%,93.3%,42.8 %,and 73.5%;respectevely.The combined model exhibited an area under the curve of 0.845(95% CI:0.798-0.892).The sensitivity,specificity,PPV,NPV,and accuracy were 84.3%,73.8%,92.6%,54.6%,and 82.1%;respectively.Calibration curves demonstrate d excellent agreement between the nomogram prediction and actual observation.The decision curve analysis showed that the c ombine d model provided greater net benefit compared to the magnetocardingraphy model.CONCLUSIONS The novel quantitative MFM parameters,whether used individually or in combination with clinical indicators,have been shown to effectively pre dict the risk of severe coronary stenosis in patients presenting with angina-like symptoms.Magnetocardiography,an emerging non-invasive diagnostic tool,warrants further exploration for its potential in diagnosing coronary heart disease.

Optimality of Group Testing with Differential Misclassification

Group testing is a method that can be used to estimate the prevalence of rare infectious diseases,which can effectively save time and reduce costs compared to the method of random sampling.However,previous literature only demonstrated the optimality of group testing strategy while estimating prevalence under some strong assumptions.This article weakens the assumption of misclassification rate in the previous literature,considers the misclassification rate of the infected samples as a differentiable function of the pool size,and explores some optimal properties of group testing for estimating prevalence in the presence of differential misclassification conforming to this assumption.This article theoretically demonstrates that the group testing strategy performs better than the sample by sample procedure in estimating disease prevalence when the total number of sample pools is given or the size of the test population is determined.Numerical simulation experiments were conducted to evaluate the performance of group tests in estimating prevalence in the presence of dilution effect.

A comparison of model choice strategies for logistic regression

Purpose:The purpose of this study is to develop and compare model choice strategies in context of logistic regression.Model choice means the choice of the covariates to be included in the model.Design/methodology/approach:The study is based on Monte Carlo simulations.The methods are compared in terms of three measures of accuracy:specificity and two kinds of sensitivity.A loss function combining sensitivity and specificity is introduced and used for a final comparison.Findings:The choice of method depends on how much the users emphasize sensitivity against specificity.It also depends on the sample size.For a typical logistic regression setting with a moderate sample size and a small to moderate effect size,either BIC,BICc or Lasso seems to be optimal.Research limitations:Numerical simulations cannot cover the whole range of data-generating processes occurring with real-world data.Thus,more simulations are needed.Practical implications:Researchers can refer to these results if they believe that their data-generating process is somewhat similar to some of the scenarios presented in this paper.Alternatively,they could run their own simulations and calculate the loss function.Originality/value:This is a systematic comparison of model choice algorithms and heuristics in context of logistic regression.The distinction between two types of sensitivity and a comparison based on a loss function are methodological novelties.

Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated.Objectives: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one another.Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022.Results: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

Energy dissipation mechanism and ballistic characteristic optimization in foam sandwich panels against spherical projectile impact

This study systematically examines the energy dissipation mechanisms and ballistic characteristics of foam sandwich panels(FSP)under high-velocity impact using the explicit non-linear finite element method.Based on the geometric topology of the FSP system,three FSP configurations with the same areal density are derived,namely multi-layer,gradient core and asymmetric face sheet,and three key structural parameters are identified:core thickness(t_(c)),face sheet thickness(t_(f))and overlap face/core number(n_(o)).The ballistic performance of the FSP system is comprehensively evaluated in terms of the ballistic limit velocity(BLV),deformation modes,energy dissipation mechanism,and specific penetration energy(SPE).The results show that the FSP system exhibits a significant configuration dependence,whose ballistic performance ranking is:asymmetric face sheet>gradient core>multi-layer.The mass distribution of the top and bottom face sheets plays a critical role in the ballistic resistance of the FSP system.Both BLV and SPE increase with tf,while the raising tcor noleads to an increase in BLV but a decrease in SPE.Further,a face-core synchronous enhancement mechanism is discovered by the energy dissipation analysis,based on which the ballistic optimization procedure is also conducted and a design chart is established.This study shed light on the anti-penetration mechanism of the FSP system and might provide a theoretical basis for its engineering application.