Unignored intracellular journey and biomedical applications of extracellular vesicles.

The intracellular journey of extracellular vesicles (EVs) cannot be ignored in various biological pathological processes. In this review, the biogenesis, biological functions, uptake pathways, intracellular trafficking routes, and biomedical applications of EVs were highlighted. Endosomal escape is a unique mode of EVs release. When vesicles escape from endosomes, they avoid the fate of fusing with lysosomes and being degraded, thus having the opportunity to directly enter the cytoplasm or other organelles. This escape mechanism is crucial for EVs to deliver specific signals or substances. The intracellular trafficking of EVs after endosomal escape is a complex and significant biological process that involves the coordinated work of various cellular structures and molecules. Through the in-depth study of this process, the function and regulatory mechanism of EVs are fully understood, providing new dimensions for future biomedical diagnosis and treatment.

Structural, physicochemical and digestive properties of non-covalent and covalent complexes of ultrasound treated soybean protein isolate with soybean isoflavone.

The non-covalent and covalent complexes of ultrasound treated soybean protein isolate (SPI) and soybean isoflavone (SI) were prepared, and the structure, physicochemical properties and in vitro digestion characteristics of SPI-SI complexes were investigated. Ultrasonic treatment increased the non-covalent and covalent binding degree of SPI with SI, and the 240 W ultrasonic covalent complexes had higher binding efficiency. Appropriate ultrasonic treatment caused more uniform particle size distribution, lower average particle size and higher surface charge, which enhanced the free sulfhydryl groups and surface hydrophobicity, thus improving the stability, solubility and emulsifying properties of complexes. Ultrasonic treatment resulted in more disordered secondary structure, tighter tertiary conformation, higher thermal stability and stronger SPI-SI covalent interactions of complexes. These structural modifications of particles had important effects on the chemical stability and gastrointestinal digestion fate of SI. The ultrasonic covalent complexation had a greater resistance to heat-induced chemical degradation of SI and improved its chemical stability. Furthermore, the 240 W ultrasonic covalent complexes showed lower protein digestibility during digestion, and provided stronger protection for SI, which improved the digestion stability and antioxidant activity. Therefore, appropriate ultrasound promoted SPI-SI interactions to improve the stability and functional properties of complexes, which provided a theoretical basis for the development of new complexes and their applications in functional foods.

Riboflavin-loaded soy protein isolate cold gel treated with combination of high intensity ultrasound and high hydrostatic pressure: Gel structure, physicochemical properties and gastrointestinal digestion fate.

Transglutaminase (TGase) was added to soy protein isolate (SPI) dispersion after the combination treatment of high intensity ultrasound (HIU) and high hydrostatic pressure (HHP) to catalyze the formation of cold gel, which was used to encapsulate riboflavin. The structure, physicochemical properties and in vitro digestion characteristics of riboflavin-loaded SPI cold gel were investigated. HIU-HHP combined treatment enhanced the strength, water retention, elastic property, thermal stability and protein denaturation degree of riboflavin-loaded SPI cold gels, and improved the gel network structure, resulting in a higher encapsulation efficiency of riboflavin and its chemical stability under heat and light treatment. HIU-HHP combined treatment reduced the erosion and swelling of SPI cold gel in simulated gastrointestinal fluid, and improved the sustained release effect of SPI gel on riboflavin by changing the digestion mode and rate of gel. In addition, HIU-HHP combined treated gels promoted the directional release of riboflavin in the simulated intestinal fluid, thereby improving its bioaccessibility, which was related to the secondary structure orderliness, tertiary conformation tightness and aggregation degree of protein during the gastrointestinal digestion. Therefore, HIU-HHP combined treatment technology had potential application value in improving the protection, sustained/controlled release and delivery of SPI cold gels for sensitive bioactive compounds.

Study on antimicrobial activity of sturgeon skin mucus polypeptides (Rational Design, Self-Assembly and Application).

Despite the favorable biocompatibility of natural antimicrobial peptides (AMPs), their scarcity limits their practical application. Through rational design, the activity of AMPs can be enhanced to expand their application. In this study, we selected a natural sturgeon epidermal mucus peptide, AP-16 (APATPAAPALLPLWLL), as the model molecule and studied its conformational regulation and antimicrobial activity through amino acid substitutions and N-terminal lipidation. The structural and morphological transitions of the peptide self-assemblies were investigated using circular dichroism and transmission electron microscopy. Following amino acid substitution, the conformation of AL-16 (AKATKAAKALLKLWLL) did not change. Following N-terminal alkylation, the C8-AL-16 and C12-AL-16 conformations changed from random coil to ß-sheet or α-helix, and the self-assembly changed from nanofibers to nanospheres. AL-16, C8-AL-16, and C8-AL-16 presented significant antimicrobial activity against Pseudomonas and Shewanella at low concentrations. N-terminal alkylation effectively extended the shelf life of Litopenaeus vannamei. These results support the application of natural AMPs.

A robotic system for transthoracic puncture of pulmonary nodules based on gated respiratory compensation.

BACKGROUND AND OBJECTIVE: With the urgent demands for rapid and precise localization of pulmonary nodules in procedures such as transthoracic puncture biopsy and thoracoscopic surgery, many surgical navigation and robotic systems are applied in the clinical practice of thoracic operation. However, current available positioning methods have certain limitations, including high radiation exposure, large errors from respiratory, complicated and time-consuming procedures, etc. METHODS: To address these issues, a preoperative computed tomography (CT) image-guided robotic system for transthoracic puncture was proposed in this study. Firstly, an algorithm for puncture path planning based on constraints from clinical knowledge was developed. This algorithm enables the calculation of Pareto optimal solutions for multiple clinical targets concerning puncture angle, puncture length, and distance from hazardous areas. Secondly, to eradicate intraoperative radiation exposure, a fast registration method based on preoperative CT and gated respiration compensation was proposed. The registration process could be completed by the direct selection of points on the skin near the sternum using a hand-held probe. Gating detection and joint optimization algorithms are then performed on the collected point cloud data to compensate for errors from respiratory motion. Thirdly, to enhance accuracy and intraoperative safety, the puncture guide was utilized as an end effector to restrict the movement of the optically tracked needle, then risky actions with patient contact would be strictly limited. RESULTS: The proposed system was evaluated through phantom experiments on our custom-designed simulation test platform for patient respiratory motion to assess its accuracy and feasibility. The results demonstrated an average target point error (TPE) of 2.46 ± 0.68 mm and an angle error (AE) of 1.49 ± 0.45° for the robotic system. CONCLUSIONS: In conclusion, our proposed system ensures accuracy, surgical efficiency, and safety while also reducing needle insertions and radiation exposure in transthoracic puncture procedures, thus offering substantial potential for clinical application.

Interlayer coupling controlled electronic and magnetic properties of two-dimensional VOCl2/PtTe2 van der Waals heterostructure.

The coupling of hetero monolayers into van der Waals (vdW) heterostructures has become an effective way to obtain tunable physical and chemical properties of two dimensional (2D) materials. In this work, based on first principles calculations, we systematically explore the electronic and magnetic properties of a 2D VOCl2/PtTe2 heterostructure. Our results indicate that the ground state of the VOCl2/PtTe2 heterostructure is a ferromagnetic (FM) metal with large magnetic anisotropy energy, among which, the VOCl2 "sublayer" shows FM half metallic properties while the PtTe2 "sublayer" shows nonmagnetic metallic properties. The Curie temperature (TC) of VOCl2/PtTe2 is 111 K. Moreover, the FM-antiferromagnetic (AFM) phase transition can be obtained under biaxial strain. Our work provides an effective way to improve the performance of 2D monolayers in nano-electronic devices.

Transglutaminase-induced soybean protein isolate cold-set gels treated with combination of ultrasound and high pressure: Physicochemical properties and structural characterization.

Soybean protein isolate (SPI) was treated by the combined exposure to ultrasound and high pressure and then subjected to transglutaminase (TGase)-catalyzed cross-linking to prepare SPI cold-set gels. The effects of combined treatments on physicochemical and structural properties of TGase-induced SPI cold-set gels were investigated. The combination of ultrasound and high pressure promoted the covalent disulfide bonds and ε-(γ-glutaminyl) lysine isopeptide bonds as well as non-covalent hydrophobic interactions, which further improved the gelation properties of SPI compared to ultrasound or high pressure alone. In particular, the 480 W ultrasound followed by high pressure treatment of gels led to higher strength (120.53 g), water holding capacity (95.39 %), immobilized water (93.92 %), lightness (42.18), whiteness (51.03), and elasticity (G' = 407 Pa), as well as more uniform and compact microstructure, thus resulting in the improved gel network structure. The combination of two treatments produced more flexible secondary structure, tighter tertiary conformation and higher denaturation degree of protein in the gels, leading to more stable gel structure. The structural modifications of SPI contributed to the improvement of its gelation properties. Therefore, the combined application of ultrasound and high pressure can be an effective method for improving the structure and properties of TGase-induced SPI cold-set gels.

The effect of switchable electronic polarization states on the electronic properties of two-dimensional multiferroic TMBr2/Ga2SSe2 (TM = V-Ni) heterostructures.

Multiferroic van der Waals (vdW) heterostructures (HSs) prepared by combining different ferroic materials offer an exciting platform for next-generation nanoelectronic devices. In this work, we investigate the magnetoelectric coupling properties of multiferroic vdW HSs consisting of a magnetic TMBr2 (TM = V-Ni) monolayer and a ferroelectric Ga2SSe2 monolayer using first-principles theory calculations. It is found that the magnetic orderings in the magnetic TMBr2 layers are robust and the band alignment of these TMBr2/Ga2SSe2 HSs can be altered by reversing the polarization direction of the ferroelectric layer. Among them, VBr2/Ga2SSe2 and FeBr2/Ga2SSe2 HSs can be switched from a type-I to a type-II semiconductor, which allows the generation of spin-polarized and unpolarized photocurrent. Besides, CrBr2/Ga2SSe2, CoBr2/Ga2SSe2 and NiBr2/Ga2SSe2 exhibit a type-II band alignment in reverse ferroelectric polarization states. Moreover, the magnetic configuration and band alignment of these TMBr2/Ga2SSe2 HSs can be further modulated by applying an external strain. Our findings suggest the potential of TMBr2/Ga2SSe2 HSs in 2D multiferroic and spintronic applications.

Portal Fibrotic Cord is Associated with Transjugular Intrahepatic Portosystemic Shunt Failure and Death in Cirrhotic Patients.

Background and Aims: Occlusive portal vein thrombosis (PVT) often causes portal hypertension-related complications in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for this difficult problem. However, the factors influencing TIPS success and overall survival in patients with occlusive PVT are unknown. This study investigated the factors influencing TIPS success and overall survival in cirrhotic patients with occlusive PVT. Methods: Cirrhotic patients with occlusive PVT were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital between January 2015 and May 2021. Baseline characteristics, TIPS success rate, complications, and survival were collected, and the factors associated with the TIPS success rate and transplant-free survival were analyzed. Results: A total of 155 cirrhotic patients with occlusive PVT were enrolled. TIPS succeeded in 126 (81.29%) cases. The 1-year survival rate was 74%. Compared with those without, patients with portal fibrotic cord had a lower TIPS success rate (39.02% vs. 96.49%, p<0.001), shorter median overall survival (300 vs. 1,730 days, p<0.001) and more operation-related complications (12.20% vs. 1.75%, p<0.01). Logistic regression analysis found that portal fibrotic cord (odds ratio 0.024) was a risk factor for TIPS failure. Univariate and multivariate analysis showed that portal fibrotic cord was an independent predictor of death (hazard ratio 2.111; 95% CI: 1.094-4.071, p=0.026). Conclusions: Portal fibrotic cord increased the TIPS failure rate and is a risk factor for poor prognosis in cirrhotic patients.

Interactions of soy protein isolate with common and waxy corn starches and their effects on acid-induced cold gelation properties of complexes.

Soy protein isolate (SPI) was mixed with different concentrations of common starch (CS) and waxy starch (WS) from corn. The interactions of SPI with CS or WS and their effects on the acid-induced cold gelation properties of complexes were investigated. Compared with WS, SPI could bind to CS more strongly and formed a tighter SPI-CS non-covalent complex, which resulted in the increased ß-sheet and a more ordered secondary structure. The gel strength, water holding capacity (WHC), viscoelasticity, hydrophobic interactions and thermal stability of SPI-CS complex gels were enhanced as increasing CS concentration, and the complex with 2% of CS had the best gelation properties. Although adding WS reduced the gel strength, rheological properties and hydrophobic interactions of SPI-WS complex gels, it improved the WHC and thermal stability of the complex gels. Therefore, CS had a broader effect on improving acid-induced cold gelation properties of SPI than WS.

Gut-derived ß-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis.

Peripheral ß-amyloid (Aß), including those contained in the gut, may contribute to the formation of Aß plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aß in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aß and several key proteins involved in Aß metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aß was detected throughout the gut in both mice and human, and gut Aß42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aß42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aß combined with vagotomy was also performed to investigate the transmission of Aß from gut to brain. The data showed that, in aged mice, the gut Aß42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aß in the brain, and gut microbiota can further upregulate gut Aß production, thereby potentially contributing to AD pathogenesis.

QT Prolongation and In-Hospital Ventricular Arrhythmic Complications in Patients With Apical Ballooning Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly high-risk of arrhythmias. OBJECTIVES: The aim of the study was to determine the association of QT interval on electrocardiogram for ventricular arrhythmic complications in patients with apical ballooning Takotsubo syndrome in a diverse population at a large urban hospital in the U.S. METHODS: We reviewed 105 cases of apical ballooning Takotsubo syndrome in patients admitted between 2011 and 2017. Two cardiologists reviewed the electrocardiograms to measure QT interval, adjusted for rate using the Fridericia formula (QTCF), and ventricular arrhythmic complications during the hospitalization. Data are reported as median and interquartile range or number and percentage. RESULTS: Of the 105 patients, 86 (82%) were female, and 34 (32%) were self-reported Black or African American. The mean age was 65 years (range: 58-72 years). Left ventricular ejection fraction was 25% (range: 25%-35%). Heart rate was 101 beats/min (range: 83-121 beats/min). Ten (11%) patients experienced a ventricular arrhythmic complication and had significantly longer QTCF (470 [range: 422-543] milliseconds) than did those without complications (417 [range: 383-456] milliseconds, P = 0.031). The area under the curve for QTCF was 0.708 (95% CI: 0.536-0.880; P = 0.031). Twenty-eight (27%) patients had a QTCF ≥460 milliseconds and significantly more arrhythmic complications (21% vs 5%, odds ratio 4.997 [95% CI: 1.288-19.237], P = 0.021). QTCF was an independent predictor of ventricular arrhythmias: odds ratio 1.090 for each 10-millisecond increase in QTCF (95% CI: 1.004-1.183; P = 0.040, corrected for sex). CONCLUSIONS: In a diverse population of patients with apical ballooning Takotsubo syndrome admitted to a large urban hospital in the United States, QTCF at admission ≥460 milliseconds identifies patients at high risk for in-hospital arrhythmic complications. Further studies are needed to determine strategies aimed at shortening QT interval to potentially prevent life-threatening arrhythmic events.

Application of a combined response surface methodology (RSM)-artificial neural network (ANN) for multiple target optimization and prediction in a magnetic coagulation process for secondary effluent from municipal wastewater treatment plants.

In this study, an enhanced coagulation-flocculant process incorporating magnetic powder was used to further treat the secondary effluent of domestic wastewater from a municipal wastewater treatment plant. The purpose of this work was to improve the discharged water quality to the surface water class IV standard of China. A novel approach using a combination of the response surface methodology and an artificial neural network (RSM-ANN) was used to optimize and predict the total phosphorus (TP) pollutant removal and turbidity. This work was first evaluated by RSM using the concentrations of coagulant, magnetic powder, and flocculant as the controllable operating variables to determine the optimal TP removal and turbidity. Next, an ANN model with a back-propagation algorithm was constructed from the RSM data along with the non-controllable variables, raw TP concentration, and raw water turbidity. Under the optimized experimental conditions (28.42 mg/L coagulant, 623 mg/L magnetic powder, and 0.18 mg/L flocculant), the TP and turbidity removal reached 88.79 ± 5.45% and 63.48 ± 9.60%, respectively, compared with 83.28% and 59.80%, predicted by the single RSM model, and 87.71 ± 5.74% and 64.62 ± 10.75%, predicted by the RSM-ANN model. The treated water were 0.17 ± 6.69% mg/L of TP and 2.46 ± 5.09% NTU of turbidity, respectively, which completely met the surface water class IV standard (TP < 0.3 mg/L; turbidity < 3 NTU). Therefore, this work demonstrated that the discharged water quality was completely improved using the magnetic coagulation process. In addition, the combined RSM-ANN approach could have potential application in municipal wastewater treatment plants.

Enhancement of algae ponds for rural domestic sewage treatment by prolonging daylight using artificial lamps.

Algal ponds (APs) are widely used as treatment facilities for domestic sewage in sparsely populated rural areas. However, few AP studies have focused on daylight length to enhance pollutants removal. In this study, four algae ponds were set up, daylight was prolonged by 0, 2, 4, and 6 h with an illuminating intensity of 3000 lx. The highest removal efficiencies of total nitrogen, ammonium, and total phosphorus were 37.36%, 41.20%, and 21.56% due to the highest microbial abundance under optimum conditions (2 h PD), respectively. Excessive PD (4 h and 6 h) could inhibit the removal abilities. PD also increased the maximum relative electron transport rate of algae, leading to an increase in the photosynthetic capacity of APs. Meanwhile, the high microbial abundance indicates that chemoheterotrophic bacteria are the main influencing factor for the removal of nitrogen and phosphorus by the APs. Moreover, the system with PD using artificial lamps was proven to be feasible for engineering applications and potentially utilized in rural domestic wastewater treatment.

Discontinuation of Transmission Precautions for COVID-19 Patients: Polymerase Chain Reaction Diagnostics, Patient Delays, and Cycle Threshold Values.

BACKGROUND: The decision of when it is safe to discontinue transmission-based precautions for SARS-CoV-2 coronavirus disease 2019 (COVID-19) hospitalized patients has been controversial. The Centers for Disease Control and Prevention offered reverse transcriptase polymerase chain reaction (PCR) diagnostic test- or symptom-based guidelines. METHODS: A retrospective chart review of Vidant Health system, Eastern North Carolina, was conducted. Length of stay, days in isolation unit, and date appropriate for discharge or isolation discontinuation based on the symptom-based strategy were recorded. RESULTS: Of 196 COVID hospitalized patients, 34 had repeated COVID PCR tests 3 or more days from their first positive test result. Half of these patients experienced delays in release from transmission-based precautions because of repeated positive PCR test results and use of the test-based approach. This resulted in an additional 166 days of hospitalization, costing an estimated $415,000. Furthermore, 2 subjects had a combined 16-day delay in necessary medical procedures. Most of the COVID PCR platforms yield quantitative results in the form of cycle threshold (Ct) values, the number of cycles needed to detect the genome. These values have also been used to assess whether patients are likely to remain contagious. None of our patients who met the criteria for symptom-based strategy for transmission-based precaution discontinuation had positive PCR test results with Ct values lower than 25, but 4 had Ct values lower than 30. CONCLUSIONS: Concerns surround immunocompromised patients and those treated with steroids who might be delayed or incapable of stopping viral replication and thus remain contagious. Our results suggest that clinicians use all available data including Ct values to evaluate the safety of discontinuation of transmission precautions.

Three-dimensional reconstruction using variable exponential function regularization for wide-field polarization modulation imaging of surface texture of particles.

Shapes from the diffuse polarization method effectively realize the three-dimensional (3D) reconstruction of the object surface by using the polarization information of the diffuse reflection light. However, due to the nonconvexity of the particle surface, the reconstruction often falls into a local optimal solution. Indeed, the depth image obtained by the scanning electron microscope has serious stripe noise, which distorts the surface texture of the particle. In this Letter, a variable exponential function regularization method is proposed to realize 3D reconstruction for the nonconvexity of the surface and inclination of the particles. We focus on the gradient unintegrability caused by the skew and surface undulation of the specimen. An adaptive 3D reconstruction method is proposed based on variable exponential function regularization to fit the surface function of the particle. Experimental results of finite-difference time-domain simulations and actual imaging demonstrate the effectiveness of the method.

Ultra-Conformable Ionic Skin with Multi-Modal Sensing, Broad-Spectrum Antimicrobial and Regenerative Capabilities for Smart and Expedited Wound Care.

While rapid wound healing is essential yet challenging, there is also an unmet need for functional restoration of sensation. Inspired by natural skin, an ultra-conformable, adhesive multi-functional ionic skin (MiS) with multi-modal sensing capability is devised for smart and expedited wound care. The base of MiS is a unique skin-like, conductive and self-adaptive adhesive polyacrylamide/starch double-network hydrogel (PSH) and self-powered, flexible, triboelectric sensor(s) is integrated on top of PSH for multi-tactile sensing. MiS could enhance wound contraction, collagen deposition, angiogenesis, and epidermis formation in a full-thickness skin defect wound model in vivo, while significantly inhibiting the biofilm formation of a wide range of microorganisms. MiS also exhibits multi-modal sensing capability for smart and instant therapeutics and diagnostics, including skin displacement or joint motion, temperature, pressure and tissue exudate changes of wound bed, and locally releasing drugs in a pH-responsive manner. More importantly, MiS could restore the skin-mimicking tactile sensing function of both touch location and intensity, and thus could be used as a human-machine interface for accurate external robotic control. MiS demonstrates a new comprehensive paradigm of combining wound diagnosis and healing, broad-spectrum anti-microbial capability and restoration of multi-tactile sensing for the reparation of severe wound.

Out of Hospital Sudden Death in a Rural Population: Low Rates of ICD Underutilization Among Decedents.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients at risk for life-threatening arrhythmias. Implantation of ICDs in rural or economically disadvantaged populations is suspected to be low. This study examined Out of Hospital Premature Natural Death (OHPND) and electronic medical record (EMR) data to identify rates of non-implantation of ICDs among decedents in eastern North Carolina. METHODS: OHPND cases in 2016 were identified using mortality data and matched with EMRs. Those meeting criteria for ICD implantation based on chart review were adjudicated by two electrophysiologists to determine whether they qualified for implantation. Comorbidity burden was established using Charlson's Comorbidity Index (CCI). RESULTS: Out of 1316 OHPND cases, 967 (73.4%) had EMR records. Chart review identified 70 (7.2%) potential ICD candidates with a LVEF ≤35 of which 5 (7.1%) did not meet criteria because LVEF subsequently improved. Of the remaining 65 patients, 32 (49.2%) already received an ICD, and 33 patients (50.7%) met criteria but had not received one. Reasons for non-implantation included: limited life expectancy secondary to comorbidities, principally chronic kidney disease (CKD) (N = 11, 17%), physician non-adherence to guidelines (N = 9, 14%), loss to follow-up (N = 7, 11%), patient refusal (N = 5, 8%), and death before commencing medical therapy (N = 1, 2%). Among our cohort of 967 individuals who died unexpectedly, nine (0.9%) patients may have avoided death with an ICD. CONCLUSION: This study using decedent data shows low rates of ICD-underutilization in a rural population and emphasizes the role of advanced comorbidities such as CKD in ICD-underutilization.