bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative increases in direct-to-consumer menthol ads following 2020 FDA guidance on flavoured e-cigarettes
Authors: Do Elizabeth K , O’Connor Katie , Diaz Megan C , Schillo Barbara A , Kreslake Jennifer M , Hair Elizabeth C
Published: February 2022

Objective

To examine potential changes in email and direct mail advertisements for flavoured e-cigarettes following the 2020 Food and Drug Administration (FDA) flavour guidance.

Methods

Digital copies of e-cigarette advertisements were obtained from Mintel Comperemedia (November 2019–May 2020) and coded for the presence of flavours. Χ2tests were used to determine changes in the prevalence of email and direct mail advertisements for e-cigarettes with menthol, non-menthol and no flavours.

Results

Following FDA guidance, the relative proportion of menthol-flavoured e-cigarette advertisements sent via email significantly increased from 22.5% to 52.2%. No changes were found for e-cigarette advertisements mentioning no flavours, nor non-menthol-flavoured e-cigarettes, sent via email or direct mail.

Conclusions

The 2020 FDA flavour guidance was followed by an increased proportion of direct-to-consumer email advertisements of menthol-flavoured e-cigarette products.
General relativity and topological string duality through Penrose–Ward transform
Authors: Hristov J.
Published: February 2022

This paper discusses the relation between topological M-theory, self-dual Yang–Mills and general relativity. We construct a topological membrane field action from Witten’s cubic string field theory, which reduces to topological Yang–Mills on a one-parameter family of conifolds. It turns out that this can be interpreted as the twistor space of the four-dimensional Lagrangian submanifold M for large momenta. From the viewpoint of the target, we find that A-model and B-model onMunify in the topological membrane theory through the Penrose–Ward transform. The partition function is constructed and it is shown that, in the weak-coupling regime, it is equal to the partition function of Donaldson-Witten theory. Additionally, homological mirror symmetry, background independence as well as role of knot cobordisms as topological two-branes is discussed. It is outlined that all types of Floer homology are part of the topological membrane theory. Additionally, we find evidence that in the non-perturbative regime, the partition function of the membrane field action and that of the partially twisted (2,0) SU(N) superconformal field theory on the worldvolume of N topological fivebranes must coincide.
Discriminating the heavy jet production mechanisms in associated Z + heavy flavor events at the LHC
Authors: Baranov S. P. , Martinez A. Bermudez , Jung H. , Lipatov A. V. , Malyshev M. A. , Monfared S. Taheri
Published: February 2022

We reconsider the associated Z boson and charm or beauty jet production at the LHC by paying special attention to the formation dynamics of heavy jets. Two different approaches are studied: first one, where heavy quarks are produced in the hard scattering subprocesses, implemented in the Monte-Carlo generator pegasus, and another method, where the hard scattering is calculated at NLO with MadGraph5_aMC@NLO and TMD parton shower is included (implemented in the Monte-Carlo generator Cascade3). We compare the predictions obtained in both schemes with latest experimental data for associated $$Z + b$$

Z
+
b

production cross sections and the relative production rate $$\sigma (Z + c)/\sigma (Z + b)$$

σ
(
Z
+
c
)
/
σ
(
Z
+
b
)

collected by the ATLAS and CMS Collaborations at $$\sqrt{s} = 13$$

s

=
13

 TeV. We introduce two kinematic observables (denoted as $$z_b$$

z
b

and $$p_T^\mathrm{rel}$$

p
T
rel

) which can be used to discriminate between the heavy jet production mechanisms. Using these variables we trace the shape of the simulated b-jet events and recommend that these observables be taken into consideration in the forthcoming experimental analyses.
Design of neuro-swarming computational solver for the fractional Bagley–Torvik mathematical model
Authors: Guirao Juan L. G. , Sabir Zulqurnain , Raja Muhammad Asif Zahoor , Baleanu Dumitru
Published: February 2022

This study is to introduce a novel design and implementation of a neuro-swarming computational numerical procedure for numerical treatment of the fractional Bagley–Torvik mathematical model (FBTMM). The optimization procedures based on the global search with particle swarm optimization (PSO) and local search via active-set approach (ASA), while Mayer wavelet kernel-based activation function used in neural network (MWNNs) modeling, i.e., MWNN-PSOASA, to solve the FBTMM. The efficiency of the proposed stochastic solver MWNN-GAASA is utilized to solve three different variants based on the fractional order of the FBTMM. For the meticulousness of the stochastic solver MWNN-PSOASA, the obtained and exact solutions are compared for each variant of the FBTMM with reasonable accuracy. For the reliability of the stochastic solver MWNN-PSOASA, the statistical investigations are provided based on the stability, robustness, accuracy and convergence metrics.
A Tale of Two Hypersecreting Adrenal Neoplasms in the Heartland of COVID-19 Pandemic, Lombardy, Italy
Authors: Zampetti Benedetta , Attanasio Roberto , Carioni Emanuela , Dallabonzana Daniela , Pauna Iuliana , Boniardi Marco , Cozzi Renato
Published: February 2022

In this study, we report the management, in Lombardy, Italy, of one patient with Cushing’s syndrome due to adrenal adenoma and another one with pheochromocytoma, whose surgeries were deferred owing to the COVID-19 pandemic.
The Iterative Inversion Method of the Gravity Interface Based on the Regular-Integral Downward Continuation Method
Authors: Wu Heyu , Du Wei , Zhang Yangyang
Published: February 2022

In computational mathematics, the iterative method is a mathematical procedure. This method uses an initial value to generate a sequence of improving approximate solutions for a class of problems, in which the n-th approximation is derived from the previous ones. The iterative method is widely used to solve complex problems in engineering. In this paper, the iterative method is applied to inverse the subsurface interface with the gravity anomaly. First, the classical Parker-Oldenburg interface inversion formula was introduced and analogized to the downward continuation formula. Then, combined with the regular-integral downward continuation method, the iterative inversion formula of the gravity interface is derived. The iterative mode of the improved method suppresses high-frequency signals effectively. At the same time, there is no need to perform forward calculations in the iterative process. The model test shows that the proposed method can accurately calculate the depth of the interface. Finally, the proposed interface inversion method is applied to the Qinghai-Tibet Plateau, and the calculated Moho interface provides some geophysical data support for the geological interpretation of the area in the future.
Successful Treatment for a Large Chronic Expanding Hematoma Treated by Pneumonectomy after Arterial Embolization
Authors: Fujiwara-Kuroda Aki , Nozomu Iwashiro  , Ohara Masanori , Kichizo Kaga
Published: February 2022

A chronic expanding hematoma is a rare late complication of thoracoplasty for tuberculosis, before the development of drugs. Total resection of a chronic expanding hematoma often requires invasive surgery consisting of combined resection of the lung and chest wall, accompanied by intraoperative bleeding. We report a case of successful surgical resection of a chronic expanding hematoma with preoperative arterial embolization, 48 years after extraperiosteal paraffin plombage for pulmonary tuberculosis. The operative indication or procedure for a chronic expanding hematoma should be determined carefully, and preoperative preparations as well as strategies should be elaborated for safe surgical resection. It is important to share information about treatment for a large chronic expanding hematoma, as we may continue to encounter this complication over the long term.
New Robust Regression Method for Outliers and Heavy Sparse Noise Detection via Affine Transformation for Head Pose Estimation and Image Reconstruction in Highly Complex and Correlated Data: Applications in Signal Processing
Authors: Liang Peidong , Likassa Habte Tadesse , Zhang Chentao
Published: February 2022

In this work, we propose a novel method for head pose estimation and face recovery, particularly to solve the potential impacts of noises in signal processing to get an efficient and effective model that is more resilient with annoying effects through adding affine transformation with the low-rank robust subspace regression. Consequently, the corrupted images can be correctly recovered by affine transformations to render more best regression outcomes. Thereby, we need to search so as to get optimal parameters which can be regarded as convex constrained optimization techniques. Afterward, the alternating direction method for multipliers (ADMM) approach is considered and a new set of updated equations is well established so as to update the optimization parameters and affine transformations iteratively in a round-robin manner. Additionally, the convergence of these new updating equations is well scrutinized as well. Thus, the experimental simulations reveal that the proposed method outperforms the state-of-the-art works for head pose estimation and face recovery on some public databases.
Exercise and Oxidative Stress Biomarkers among Adult with Cancer: A Systematic Review
Authors: Longobucco Yari , Masini Alice , Marini Sofia , Barone Giuseppe , Fimognari Carmela , Bragonzoni Laura , Dallolio Laura , Maffei Francesca
Published: February 2022

Evidence shows that exercise can have a favourable effect in cancer patients. The exercise’s clinical benefits are likely to concern multiple interrelated biological pathways, among which oxidative stress plays a key role. Regular training can induce an adaptive response that strengthens the antioxidative status of the body. To formulate public health recommendations regarding the optimal exercise prescription for cancer patients, a detailed understanding is needed regarding the effect of exercise on variables linked to oxidative stress and antioxidant status of patients. The goal of this systematic review, based on PRISMA, was to explore and critically analyse the evidence regarding the efficacy of exercise on oxidative stress biomarkers among people with cancer. Study search was conducted in the following databases: PubMed, Cochrane, CINAHL, Embase, PEDro, and SPORTDiscus. The studies’ quality was assessed with the Cochrane risk-of-bias tool and STROBE scale. After identification and screening steps, 10 articles were included. The findings provide an encouraging picture of exercise, including resistance training and aerobic activities, in people with cancer. The exercise improved the indicators of the total antioxidant capacity, increased the antioxidant enzymes’ activity, or reduced the biomarkers of oxidative damage in various forms of cancer such as breast, lung, head, and neck. Regarding oxidative DNA damage, the role of exercise intervention has been difficult to assess. The heterogeneity of study design and the plethora of biomarkers measured hampered the comparison of the articles. This limited the possibility of establishing a comprehensive conclusion on the sensitivity of biomarkers to estimate the exercise’s benefits. Further high-quality studies are required to provide data regarding oxidative stress biomarkers responding to exercise. This information will be useful to assess the efficacy of exercise in people with cancer and support the appropriate prescription of exercise in anticancer strategy.
Shufeiya Recipe Improves Monocrotaline-Induced Pulmonary Hypertension in Rats by Regulating SIRT3/FOXO3a and Its Downstream Signaling Pathways
Authors: Jia Zhuangzhuang , Yan Haifeng , Wang Shuai , Wang Lin , Cao Yawen , Lin Shanshan , Zhang Zeyu , Wang Ci , Wang Xianliang , Mao Jingyuan
Published: February 2022

Pulmonary hypertension (PH) is a chronic and progressive disease caused by obstructions and functional changes of small pulmonary arteries. Current treatment options of PH are costly with patients needing long-term taking medicine. The traditional Chinese medicine (TCM) compound “Shufeiya Recipe” was used to intervene in monocrotaline- (MCT-) induced pulmonary hypertension in rats. The rats were randomly divided into the control group, model group, positive drug (Sildenafil) group, and Shufeiya Recipe low-, moderate-, and high-dose groups. The improvement effect of the Shufeiya Recipe on the mean pulmonary artery pressure (mPAP) was assessed in PH rats, and pathological staining was used to observe the pathological changes of lung tissue. The impact of the Shufeiya Recipe on oxidative stress damage in rats with pulmonary hypertension and the regulation of SIRT3/FOXO3a and its downstream signaling pathways were determined. The results showed that Shufeiya Recipe could significantly downregulate mPAP and improve lung histopathological changes; downregulate serum levels of reactive oxygen species (ROS); upregulate the concentrations of COX-1 and COX-2 and the activity of Mn-SOD; inhibit oxidative response damage; promote the protein expression of SIRT3, FOXO3a, p-PI3K, p-AKT, and p-eNOS; increase the level of expression of NO, sGC, cGMP, and PKG; and downregulate the level of protein expression of Ras, p-MEK1/2, p-ERK1/2 and c-fos. These results indicate that Shufeiya Recipe can improve MCT-induced pulmonary hypertension in rats by regulating SIRT3/FOXO3a and its downstream PI3K/AKT/eNOS and Ras/ERK signaling pathways.
Effect of Graded Levels of Dietary Emamectin Benzoate on Immunity, Enzyme Activity, and Withdrawal Period in Labeo rohita Juveniles (Hamilton, 1822)
Authors: Choudhary Pushpa , Swain Priyabrat , Das Rakesh , Sahoo Satya Narayan , Das Krushna Chandra , Patil Prasanna Kumar , Mishra Sudhansu Sekhar
Published: February 2022

This study was conducted to evaluate the effect of dietary emamectin benzoate (EB) levels on immune responses, serum enzyme activities, and retention of EB in muscle tissue to establish the withdrawal period in rohu, Labeo rohita juveniles (avg. wt.

18
±
0.11

 g). To ascertain this, 450 healthy L. rohita juveniles were fed with EB in graded doses viz., at 50 (1x), 125 (2.5x), 250 (5x), and 375 (7.5x) μg kg-1 of fish biomass day-1, respectively, in triplicate for 21 days through a basal feed. Upon completion of 21 days, the same experimental fish were fed with basal feed (without EB) for another 14 days to measure the retention of EB in the muscle tissue. Each 7-day interval, five fish were randomly sampled. The results showed that respiratory burst activity, myeloperoxidase activity, bacterial haemagglutination, and haemolysis activities were improved significantly (

p
<
0.05

) in 1x and 2.5x dose fed group from 7th day onwards until 14th day. Few selected enzyme activities viz., LDH and ALP were found to be significantly (

p
<
0.05

) high in the fish fed with EB at 5x and 7.5x dose compared to 1x. The LC-MS/MS study of the experimental fish discloses that EB was retained in muscle tissue at a dose-dependent manner and significantly (

p
<
0.05

) lowest level (

0.341
±
0.03

 ppb) was retained in the fish fed with 1x dose of EB. Hence, 1x dose of EB may be adhered to treat L. rohita juveniles through feed with 14 days of withdrawal period.
Risk Assessment and Prediction of Rainstorm and Flood Disaster Based on Henan Province, China
Authors: Deng Guoqu , Chen Hu , Wang Siqi
Published: February 2022

To reasonably evaluate and predict the loss of rainstorm and flood disaster, this study is based on the rainfall data and rainstorm and flood disaster data of 18 cities in Henan Province from 2010 to 2020, using GIS technology and weighted comprehensive evaluation method to analyze the risk of rainstorm and flood disaster factors in various regions. The four risk factors of hazard risk, hazard-pregnant environment sensitivity, hazard-bearing body vulnerability, and disaster resilience were analyzed in compartment analysis. At the same time, a new rainstorm and flood disaster prediction model was constructed in combination with the hybrid PSO-SVR algorithm. The research results show that there are many rivers in Henan Province, the terrain tends to be higher in the west and lower in the east, and most areas are low plains, making most cities in Henan Province at a moderate risk level. For the more developed cities such as Zhengzhou, Luoyang, and Nanyang, the hazard risk, sensitivity, vulnerability, and disaster resistance are high, and they are prone to heavy rains and floods. For the economically underdeveloped, the terrain is high or hills, such as Sanmenxia City; Xinyang City and other places have low hazard risk and are not prone to rainstorms and floods. By constructing a hybrid PSO-SVR model, selecting two representative cities of Zhengzhou and Luoyang, and predicting the daily rainfall, the number of disasters, and the direct economic loss, the calculated RMSE and MAPE values are both less than GA-SVR, the traditional SVR, and BPNN models, which have verified the superiority of the model proposed in this study and the practical value it brings. To further verify the prediction accuracy of the hybrid model, the average value of RMSE and MAPE of other 16 cities are calculated, and the result is still smaller than other three models, and the study can provide some decision-making references for the urban rainstorm and flood management.
Opium Use and Cancer Risk: A Comprehensive Systematic Review and Meta-Analysis of Observational Studies
Authors: Mansouri Masoume , Naghshi Sina , Parsaeian Mahbobeh , G Sepanlou Sadaf , Poustchi Hossein , Momayez Sanat Zahra , Sadeghi Omid , Pourshams Akram
Published: February 2022

Background. Epidemiological studies have reported inconsistent associations between opium use and cancer risk. We therefore conducted a systematic review and meta-analysis to investigate the relationship between opium use and cancer risk. Methods. We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until February 2021 and references of retrieved relevant articles for observational studies that reported the risk of cancer in relation to opium use. Random-effects models were used to calculate pooled effect sizes (ESs) as well as 95% confidence intervals (CIs) for the association between opium use and cancer risk by considering opium doses and types, duration of consumption, and routes of opium use. Results. In total, 21 observational articles, with a total sample size of 64,412 individuals and 6,658 cases of cancer, were included in this systematic review and meta-analysis. Ever opium users, compared with never opium users, had 3.53 times greater risk of overall cancer (pooled ES: 3.53, 95% CI: 2.60–4.79,

P

 ≤ 0.01). This positive association was also seen for some individual types of cancers except for esophageal and colon cancers. Also, we found that higher opium doses and higher duration of consumption were associated with an increased risk of overall and individual types of cancer. However, the associations between opium doses and the risk of head and neck and larynx cancers were not significant. In terms of the routes of opium use, both opium ingestion and smoking were positively associated with the risk of cancer. Regarding opium types, we found that using teriak, but not shireh, could increase the risk of cancer. Conclusions. Our findings showed that opium use, particularly in the form of teriak, is a risk factor for cancer.
Model of Epidemic Kinetics with a Source on the Example of Moscow
Authors: Borovsky Andrey V. , Galkin Andrey L.
Published: February 2022

A new theoretical model of epidemic kinetics is considered, which uses elements of the physical model of the kinetics of the atomic level populations of an active laser medium as follows: a description of states and their populations, transition rates between states, an integral operator, and a source of influence. It is shown that to describe a long-term epidemic, it is necessary to use the concept of the source of infection. With a model constant source of infection, the epidemic, in terms of the number of actively infected people, goes to a stationary regime, which does not depend on the population size and the characteristics of quarantine measures. Statistics for Moscow daily increase in infected is used to determine the real source of infection. An interpretation of the waves generated by the source is given. It is shown that more accurate statistics of excess mortality can only be used to clarify the frequency rate of mortality of the epidemic, but not to determine the source of infection.
An EEG Classification-Based Method for Single-Trial N170 Latency Detection and Estimation
Authors: Zang Siyuan , Ding Xiaojun , Wu Meihong , Zhou Changle
Published: February 2022

Event-related potentials (ERPs) can reflect the high-level thinking activities of the brain. In ERP analysis, the superposition and averaging method is often used to estimate ERPs. However, the single-trial ERP estimation can provide researchers with more information on cognitive activities. In recent years, more and more researchers try to find an effective method to extract single-trial ERPs, because most of the existing methods have poor generalization ability or suffer from strong assumptions about the characteristics of ERPs, resulting in unsatisfactory results under the condition of a very low signal-to-noise ratio. In this paper, an EEG classification-based method for single-trial ERP detection and estimation was proposed. This study used a linear generated EEG model containing templates of ERP local descriptors which include amplitude and latency, and this model can avoid the invalid assumption about ERPs taken by other methods. The purpose of this method is not to recover the whole ERP waveform but to model the amplitude and latency of ERP components. This method afterwards examined the three machine learning models including logistic regression, neural network, and support vector machine in the EEG signal classification for ERP detection and selected the best performed MLPNN model for detection. To get the utmost out of information produced in the classification process, this study also used extra information to propose a new optimization model, with which outperformed detection results were obtained. Performance of the proposed method is evaluated on simulated N170 and real P50 data sets, and the results show that the model is more effective than the Woody filter and the SingleTrialEM algorithm. These results are also consistent with the conclusion of sensory gating, which demonstrated good generalization ability.
3D-Slicer Software-Assisted Neuroendoscopic Surgery in the Treatment of Hypertensive Cerebral Hemorrhage
Authors: Liao Rongfang , Liu Longmao , Song Bo , Wan Xinhong , Wang Shuo , Xu Jianhong
Published: February 2022

Objective. To explore the 3D-slicer software-assisted endoscopic treatment for patients with hypertensive cerebral hemorrhage. Methods. A total of 120 patients with hypertensive cerebral hemorrhage were selected and randomly divided into control group and 3D-slicer group with 60 cases each. Patients in the control group underwent traditional imaging positioning craniotomy, and patients in the 3D-slicer group underwent 3D-slicer followed by precision puncture treatment. In this paper, we evaluate the hematoma clearance rate, nerve function, ability of daily living, complication rate, and prognosis. Results. The 3D-slicer group is better than the control group in various indicators. Compared with the control group, the 3D-slicer group has lower complications, slightly higher hematoma clearance rate, and better recovery of nerve function and daily living ability before and after surgery. The incidence of poor prognosis is low. Conclusion. The 3D-slicer software-assisted endoscopic treatment for patients with hypertensive intracerebral hemorrhage has a better hematoma clearance effect, which is beneficial to the patient’s early recovery and reduces the damage to the brain nerve of the patient.
Entropy and Heat Transfer Analysis for MHD Flow of

C
u

/

A
g

-Water-Based Nanofluid on a Heated 3D Plate with Nonlinear Radiation
Authors: Eswaramoorthi S. , Divya S. , Faisal Muhammad , Namgyel Ngawang
Published: February 2022

This paper scrutinizes the consequences of radiation and heat consumption of MHD convective flow of nanofluid on a heated stretchy plate with injection/suction and convective heating/cooling conditions. The nanofluid encompasses with

C
u

and

A
g

nanoparticles. We enforce the suited transformation to remodel the governing mathematical models to ODE models. The HAM (homotopy analysis method) idea is applied to derive the series solutions. The divergence of fluid velocity, temperature, skin friction coefficient, local Nusselt number, entropy generation, and Bejan number on disparate governing parameters is exhibited via graphs and tables. It is seen that the fluid velocity in both directions is subsided when elevating the magnetic field and Forchheimer number. Also, the

C
u

nanoparticles possess hefty speed compared to

A
g

nanoparticles because the density of

A
g

nanoparticles is high compared to that of

C
u

nanoparticles. The fluid temperature upturns when enlarging the heat generation and radiation parameters. The skin friction coefficients and local Nusselt number are high in

A
g

nanoparticles than in

C
u

nanoparticles.
Hyaluronic Acid Modified Curcumin-Loaded Chitosan Nanoparticles Inhibit Chondrocyte Apoptosis to Attenuate Osteoarthritis via Upregulation of Activator Protein 1 and RUNX Family Transcription Factor 2
Authors: Wang Jian , Zhang Liaoran , Zhu Jiaxue , Gu Jianhua , Wang Xiang , Tao Hairong
Published: February 2022

Hyaluronic acid (HA) and curcumin (CUR) have been previously utilized for osteoarthritis (OA) treatment. CUR-loaded chitosan nanoparticles (CUR@CS NPs) and HA CUR@CS NPs were synthesized in our research to ascertain the synergistic impacts of HA and CUR-loaded NPs on OA treatment. CUR@CS
NPs and HA CUR@CS NPs were synthesized with evaluation of their particle size, potential, PDI, encapsulation efficiency, drug loading and surface coating as well as HA binding rate. The in vitro CUR release curve and stability of HA-CUR@CS NPs were measured. Chondrocytes were isolated
from the cartilages of OA patients, followed by cell uptake assay. The chondrocyte viability and apoptosis were determined. Subsequently, the knee OA model was established, followed by H&E, Safranin O/Fast green staining and micro-CT. HA CUR@CS NPs improved CUR stability and bioavailability.
CUR@CS NPs and HA-CUR@CS NPs were successfully characterized and could further be internalized by chondrocytes. CUR@CS NPs promoted tBHP-induced chondrocyte viability and inhibited chondrocyte apoptosis. HA-CUR@CS NPs upregulated the AP-1 and RUNX2 transcription levels to activate Hedgehog
pathway, which subsequently blocked the Notch pathway. Mechanically, HA-CUR@CS NPs sustained release and long-lasting effect and long-term retention in the joint cavity and downregulated the expression of several pro-inflammatory cytokines in vivo. HA-CUR@CS NPs exhibited superior effects
in the preceding experiments than CUR@CS NPs. Altogether, HA-CUR@CS NPs may restrict inflammation and chondrocyte apoptosis in OA through upregulation of AP-1 and RUNX2.
Itraconazole for Topical Treatment of Skin Carcinogenesis: Efficacy Enhancement by Lipid Nanocapsule Formulations
Authors: El-Sheridy Nabila A. , El-Moslemany Riham M. , Ramadan Alyaa A. , Helmy Maged W. , El-Khordagui Labiba K.
Published: February 2022

Itraconazole (ITC), an antifungal drug with anticancer activity, shows potential for oral treatment of skin cancer. There is clinical need for topical ITC for treating low-risk skin carcinogenesis. Our objective was to develop ITC nanoformulations with enhanced anticancer efficacy.
Lipid nanocapsules (LNC), either unmodified (ITC/LNC) or modified with the amphiphiles miltefosine (ITC/MF-LNC) or the lipopeptide biosurfactant surfactin (ITC/SF-LNC) as bioactive additives were developed. LNC formulations showed high ITC entrapment efficiency (>98%), small diameter (42–45
nm) and sustained ITC release. Cytotoxicity studies using malignant SCC 9 cells and normal human fibroblasts (NHF) demonstrated significant enhancement of ITC anticancer activity and selectivity for cancer cells by the LNC formulations and a synergistic ITC-amphiphile interaction improving
the combination performance. Treatment of intradermal tumor-bearing mice with the ITC nanoformulation gels compared with ITC and 5-FU gels achieved significant tumor growth inhibition that was remarkably enhanced by ITC/MF-LNC and ITC/SF-LNC as well as recovery of skin architecture. Molecularly,
tumoral expression of Ki-67 and cytokeratin proliferative proteins was significantly suppressed by LNC formulations, the suppressive effect on cytokeratins was superior to that of 5-FU. These findings provide new evidence for effective topical treatment of low-risk skin carcinogenesis utilizing
multiple approaches that involve drug repurposing, nanotechnology, and bioactive amphiphiles as formulation enhancing additives.
Effect of Olive Oil Acidity on Skin Delivery of Diclofenac: In Vitro Evaluation and Ex Vivo Skin Permeability Studies
Authors: Shalaby Khaled
Published: February 2022

Olive oil is a vegetable oil which has been successfully used as a skin penetrating agent. Acidity of olive oil is considered as one of the characteristic properties of olive oil. Olive oil acidity was selected as a parameter under investigation for evaluation of skin permeability.
The acidities of the three investigated olive oils are varying from 0.75±0.16 to 2±0.17. Olive oil with acidity equals 2.0 showed the highest skin permeation for 12 h and cutaneous deposition with significant difference compared to the permeation values of 0.75 and F1.4 acidities.
Results of cutaneous secretion of cytokines suggested that higher penetration was accompanied higher cytokines’ secretions. Olive oil with acidity equals 2.0 also showed more prominent skin changes which suggested to be due to acidity and fatty acids’ content. These results suggest
that olive oil might improve the epidermal permeability, which is more pronounced in highly acidic olive oil, through weakening of skin barriers followed by acting of cytokines on re-building effective barriers. Finally, based on the current study, highly acidic olive oil is more efficient
skin permeation enhancer vehicle than less acidic ones and can be efficiently used in formulation of cutaneous drug delivery systems.
Effect of Hypoxia-Inducible Factor-1α on Osteogenesis of Titanium Dioxide Nanotube Bone Marrow Mesenchymal Stem Cells with Different Diameters Under Periodic Tensile Stress
Authors: Meng Yu , Chen Juwu , Wu Xuejian
Published: February 2022

Bone marrow mesenchymal stem cells (BMSC) have the ability to multi polarize with multiple tropisms and participate in tissue remodeling. This study assessed the effect of titanium dioxide nanotubes with different diameters on ossification of BMSC cells and HIF-1α expression
in BMSC ossification. Titanium dioxide nanotubes with different diameters were prepared and then the following groups were set according to the size of pressure; Ti group, NT10 group, NT30 group, and NT60 group. Analysis of cell morphology was done by fluorescence microscope, while adhesion
and proliferation were assessed by MTT assay. Moreover, ALP activity, collagen secretion and outer matrix mineralization and expression of HIF-1α, VEGF, and TWIST were assessed by RT-PCR and Western blot. The P3 generation of BMSC cells was successfully obtained. Three types of
nanotubes were arranged regularly and contact angle showed NT60<NT30<NT10Ti>NT30>NT60 (P < 0.05). Cells from NT30 and N60 groups showed obvious expansion with pseudopodia and pseudo plates of cells. Cell adhesion showed changes
in sizes of NT10>Ti>NT30>NT66. NT60 group showed lower cell proliferation and higher ALP activity and collagen secretion than the other groups. NT30 and NT60 group presented higher mineralization level, larger diameter, and higher degree of promotion. The NT30 group presented lowest
content of HIF-1α (0.12 ± 0.03), VEGF (0.013 ± 0.004), and TWIST (0.014 ± 0.003). Inoculation of BMSCs on titanium dioxide nanotubes of different diameters under cyclical tensile stress environment can promote growth of BMSC cells in a diameter-dependent manner.
Rapid and Label-Free Prenatal Detection of Down’s Syndrome Using Body Fluid Surface Enhanced Raman Spectroscopy
Authors: Wu Qiong , Zheng Lin , Huang Hailong , Lin Huijing , Lin Xueliang , Xu Liangpu , Chen Rong , Lin Duo , Chen Guannan
Published: February 2022

Down’s syndrome (DS) is the leading genetic cause of intellectual disability. In this work, the surface enhanced Raman spectroscopy (SERS) was used for the detection of amniotic fluid and plasma from pregnant women with DS fetus for the first time. High-quality and characteristic
spectral features of amniotic fluid and plasma samples from DS groups can be obtained in comparison to normal group. Moreover, principal component analysis with linear discriminant analysis was applied to generate the efficient diagnostic model, achieving accuracies of 94.3% and 88.5% for
the DS detection with amniotic fluid and plasma samples, respectively. This preliminary study would provide a novel, convenient and accurate prenatal test based on blood SERS technology for clinical DS screening.
Evaluation of the Efficacy, Biocompatibility, and Permeation of Bupivacaine-Loaded Poly(epsilon-caprolactone) Nano-Capsules as an Anesthetic
Authors: Zhao Wangcheng , Du Yan , Ashfaq Shameen , Ali Shafaqat , Alanazi Amer M. , Santi Moreno
Published: February 2022

In this study bupivacaine (BVC) was encapsulated in Nano-capsules of poly-ε-caprolactone (PCL) and its cytotoxicity in HaCaT (MTT) cells, its permeability in the oesophageal epithelium of pigs, as well as its anesthetic effect in the incision model of rat’s hind paw
(electronic von Frey anesthesiometer) were evaluated. BVC and epinephrine-associated bupivacaine (BVC-Epi) have been compared to BVC-Nano and it was demonstrated that BVC-Nano had high physicochemical properties and remained stable for 120 days; also, encapsulation of bupivacaine did not affect
its toxicity to HaCaT cells, but epinephrine reduced its toxicity. Although both methods of combination with epinephrine and encapsulation in nanocapsules resulted in an extended time of anesthesia, the efficacy of epinephrine was more favorable. The permeation evaluation indicated that encapsulation
increased both the permeability coefficient and the steady-state flux of bupivacaine across the esophageal epithelium. BVC permeation was enhanced by encapsulation into Nano-capsules, as a new novel therapeutic strategy, facilitating future research as a topical anesthetic.
Radionanomedicine: Advanced Strategy for Precision Theranostics of Breast Cancer
Authors: Guo Yang , Liu Xiaoying
Published: February 2022

Breast carcinoma remains one of the most common and fatal cancers, and even though a series of general therapeutic approaches have been used to treat breast cancer, their outcomes are significantly affected by a variety of side effects. However, nanomedicine could offer novel strategies
for dealing with breast carcinoma. In fact, an increasing number of radionanomedicine approaches have recently been used in both diagnostics and therapy. To highlight this trend, the aim of the current review is to systemically summarize the latest advances in radionanomedicine, including
single-modular imaging, multiple-modular imaging, and nanomedicine-based theranostics. Barriers to clinical application, the development of next-generation radionanomedicine, and challenges associated with future design are also discussed.
Prostate-Specific Membrane Antigen-1-Mediated Au@SiO2@Au Core–Shell Nanoparticles: Targeting Prostate Cancer to Enhance Photothermal Therapy and Fluorescence Imaging
Authors: Wang Ruizhi , Zhou Guofeng , Yang Yuchan , Wang Shiqing , Gao Shanshan , Gao Dongmei , Wang Xiaolin
Published: February 2022

The advantages of deep tissue penetration and the high spatial accuracy of photothermal therapy have been widely studied. Gold, as a photothermal material, has received particular attention. Different sizes and shapes of gold have been studied and characterized for their varying photothermal
properties. The core–shell structure of gold nanoparticles and silica enhances the photothermal conversion through the coupling effect between gold clusters on the material’s surface. With excellent photothermal conversion performance, the core–shell nanoparticles can quickly
reach 40 °C in 200 s under the irradiation of 808 nm, 1.5 W·cm−2. The highest conversion temperature of these nanoparticles is 56 °C, and the photothermal conversion rate is 45%. In vitro cell experiments displayed that NPs with targeted function can
efficiently aggregate in prostate cancer cells and effectively kill cells. In vitro experiments showed that the tumor cells of mice after photothermal treatment completely disappeared after 15 days, which fully demonstrated the potential of the nanoparticles for targeted photothermal
therapy.
Lateral Flow Strip Assay for Detection of Mycoplasma hyorhinis Based on a Pair of Sandwich-Type Aptamers
Authors: Zhang Yibin , Dai Jing , Yang Yuan , Guo Junxiao , Cao Lanqin , Ye Mao
Published: February 2022

Mycoplasma hyorhinis is a normal flora in swine respiratory tract and also often found in multiple human tumor tissues, which is considered to be highly correlated with human tumors. Due to the detection of Mycoplasma hyorhinis mainly relies on PCR-based assay at present,
thus it is critical for developing a novel assay for rapid detection and providing support diagnosis evidence. In our work, we screened and characterized a high affinity aptamer zyb1 that can recognize Mycoplasma hyorhinis based on infectious cell-SELEX. On this basis, we developed
a lateral flow strip assay by using zyb1 and another aptamer AP15-1 to form a sandwich-type aptasensor. Using this new lateral flow strip assay biosensor, Mycoplasma hyorhinis could be detected within the detectable limit as low as 1 × 103 CCU/mL. Therefore, our study
successfully developed a convenient and effective lateral flow strip for Mycoplasma hyorhinis detection and demonstrated the potential of utilizing aptamer for the development of point-of-care testing products for mycoplasma detection.
Effect of microRNA-455-5p (miR-455-5p) on the Expression of the Cytokine Signaling-3 (SOCS3) Gene During Myocardial Infarction
Authors: Zhang Zaiyong , Luo Wenzhi , Han Yuanyuan , Misrani Afzal , Chen Hanwei , Long Cheng
Published: February 2022

To explore the effect of microRNA-455-5p (miR-455-5p) and Cytokine Signaling-3 (SOCS3) expression, a model of the cell damage induced during myocardial infarction was established using H2O2. The cell counting Kit-8 (CCK-8) and quantitative reverse transcriptase-polymerase
chain reaction (qRT-PCR) assays were used to detect the cell viability and the expression of miR-455-5p and SOCS3 in cells cultured with different concentrations of H2O2. After the selection of the optimum culture concentration, a dual-luciferase reporter gene assay was
used to detect the binding between and miR-455-5p and its potential target SOCS3. SOCS3 siRNA was transfected into cardiomyocytes using chitosan nanoparticles as a gene carrier, which led to the knockdown of SOCS3 expression, and the cells were transfected with miR-455-5p mimics and inhibitors.
The expression of cardiac protective proteins was detected by western blotting, cell viability was detected by CCK8, and cell apoptosis was detected by flow cytometry. The aim of this study was to investigate the effect of miR-455-5p and SOCS3 expression on the activity and apoptosis of damaged
cardiomyocytes, and to identify any protective effect on cardiomyocytes. Finally, after the simultaneous overexpression of SOCS3 and miR-455-5p, and the expression of cardiac protective proteins, cell activity, and apoptosis rate were detected. The results showed that the expression of miR-455-5p
decreased in a concentration-dependent manner and that the expression of SOCS3 increased in a concentration-dependent manner when the cells were cultured in different concentrations of H2O2. The knockdown of SOCS3 expression promoted an increase in cell activity, an increase
in cardiac protective proteins, and a decrease in apoptosis. The upregulation of miR-455-5p significantly inhibited the expression of SOCS3, increased cell activity, inhibited apoptosis, and exerted protective effects in myocardial cells. The overexpression of SOCS3 reversed the inhibition
of SOCS3 by miR-455-5p and reduced the protective effect of miR-455-5p on myocardial cells. Therefore, this study showed that the upregulation of miR-455-5p significantly inhibited the expression of SOCS3 and resulted in the increased protection of cells damaged by H2O2,
which was used as a model of myocardial infarction. These results indicate the potential of miR-455-5p in myocardial protection, suggesting that miRNA may be a resource for myocardial therapy.
Hyaluronic Acid-Melatonin Nanoparticles Improve the Dysregulated Intestinal Barrier, Microbiome and Immune Response in Mice with Dextran Sodium Sulfate-Induced Colitis
Authors: Jing Wanghui , Zhu Min , Wang Fushuo , Zhao Xinxin , Dong Sijing , Xu Yinyue , Wang Sicen , Yang Jianhai , Wang Ke , Liu Wenguang
Published: February 2022

Although the cause of inflammatory bowel disease (IBD) is unclear, current studies have found that the main factors involved in its pathogenesis include imbalance of mucosal immune response, intestinal dysbiosis, and destruction of the intestinal barrier. We synthesized an amphiphilic conjugate of hyaluronic acid (HA) and melatonin (MT), which have established immunomodulatory and antioxidant properties, by stimulating their nano-aggregation. Inducing colitis by dextran sodium sulfate (DSS), HA-MT accumulated in the inflamed colon epithelium of colitis mice, and markedly improved the colitis symptoms, repaired the damaged intestinal barrier and inhibited colon inflammation. In addition, through bacterial 16S rDNA sequencing, it was found that HA-MT can restore the ratio ofFirmicutes/Bacteroidetesby increasing the overall microbial richness and diversity, and alleviate the intestinal dysbiosis of mice with colitis. In the analysis of the intestinal flora at the species level, the abundance ofLactobacillusincreased in colitis mice treated with HA-MT while that ofBacteroides,BlautiaandStreptococcusdecreased in the colitis mice treated with HA-MT. Our findings suggest that the HA-MT system is a promising prebiotic, which can relieve the symptoms of IBD by regulating the intestinal microflora and restoring intestinal homeostasis, inhibiting inflammation.
Reactive Oxygen Species-Responsive Polyether Micelle Nanomaterials for Targeted Treatment of Ulcerative Colitis
Authors: Zhao Xin-Xin , Ma Shan-Bo , Wen Jin-Peng , Hu Da-Tao , Gao Ju-Shan , Peng Qiao , Zhang Yu-Chen , Wang Jin-Qing , Wang Ke , Shi Xiao-Peng
Published: February 2022

As one of the most challenging inflammatory diseases, the incidence of ulcerative colitis (UC) is increasing year by year, but the existing therapeutic drugs are not effective and lack of targeting. Nanomaterials are expected to become promising delivery system due to their good targeting
effects. Here, we designed a nanomaterial sensitive to reactive oxygen species, which can be used to treat IBD, especially UC. It is a self-assembled polyether micelle that can be oxidized at the inflammation site where the concentration of reactive oxygen increases, and effectively release
the encapsulated budesonide (Bud). Experiments have proved that for DSS-induced colitis, the synthetic drug-loaded nanoparticles have excellent therapeutic effects, can effectively repair intestinal barrier, and significantly improve the damaged colon tissue. At the same time, it has a beneficial
regulatory effect on inflammatory factors. Molecular mechanism studies have shown that it achieves its therapeutic effects by activating the peroxisome proliferators-activated receptors-γ (PPAR-γ) pathway and inhibiting the nuclear factor (NF)-κB pathway.
This study proves that oral nano-micelles have an important impact on improving the efficacy of UC treatment drugs and have far-reaching significance for the targeted treatment of gastrointestinal diseases.
Study on the Influence of Shear Stress and Pulse Electrical Stimulation to the Growth of Cardiomyocytes
Authors: Xu Junwei , Feng Limin , Wang Jingxi , Liu Meili , Li Ping , Fan Yubo
Published: February 2022

Engineered myocardial tissue is expected to be used in the treatment of myocardial defects and other diseases, and one of the keys is to construct a suitable environment for the culture of myocardial tissuein vitro. In this study, flow shear stress and pulse electrical stimulation were applied to cardiomyocytes with a self-designed device by simulating the mechanical and electrical physiological microenvironment of myocardial tissue. The strength and duration of pulse electrical stimulation as well as the intensity of shear stress were studied in detail to optimize the experimental parameters. Concretely, 100 mV pulse electrical stimulation (1 Hz and 10 ms pulse width) and 10 dyn/cm2shear stress were used for studying the influence of combined mechanical-electrical stimulation to the growth of cardiomyocytes. The mechanical factor of the combined stimulation promoted the expression ofα-cardiac actin mRNA, the electrical factor caused an increase in Cx-43 mRNA expression, and shear stress and pulse electrical stimulation showed a synergistic action on the expression of GATA-4 mRNA. It indicated that combined mechanical-electrical stimulation had a better effect on the functionalized culture of cardiomyocytes, which provided an important theoretical basis for the further construction ofin vitroengineered myocardial tissue.
A Novel Targeted Delivery of Valeric Acid Using Liposomal Nanoparticles in Treatment of Lung Cell Carcinoma
Authors: Chen Hongdou , Wan Jinxiang , Chen Douren
Published: February 2022

With a high mortality rate, non-small cell lung cancer (NSCLC) is a major challenge for patients and clinicians. The high cost and side effects of chemo-drugs severely influence disease outcome. With advantages of action prolongation and solitary target for embedded drugs, liposomal
nanoparticle-based modification was investigated in this study with valeric acid, aimed at exploring its impacts and value on NSCLC. The efficacy comparisons of chemo-drugs (cisplatin, paclitaxel and liposomal nanoparticle-modified valeric acid) were conducted utilizing human NSCLC cell lines,
normal lung fibroblasts, pulmonary epithelial cell line, and mouse tumor models. Additionally, the underlying therapeutic mechanisms for this novel liposomal nanoparticle in NSCLC were also explored via analysis of protein changes in tumor tissues. Results showed that, in comparison with conventional
chemotherapeutics (cisplatin and paclitaxel), novel liposomal nanoparticle-modified valeric acid effectively retarded the growth of human NSCLC cell lines to a greater extent, and even successfully restrained further progression of tumor tissues in vivo. Furthermore, this novel liposomal
nanoparticle-modified valeric acid exhibited lower cytotoxicity towards normal lung cell lines. Additionally, the anti-cancer function of this novel liposomal nanoparticle-modified valeric acid was found to be related to STAT3/Cyclin D1 pathway. The current study confirmed that, compared with
cisplatin and paclitaxel, this novel liposomal nanoparticle-modified valeric acid displayed significant therapeutic effect on NSCLC, with lower cytotoxicity to normal cells. It has therefore further promoted research progress and significance on NSCLC research in the clinical management of
NSCLC.