Minor Changes in Response Modules Leading to a "U-Shaped" Conversion Rate of Docetaxel Prodrug Nanoassemblies.

The prodrug-based nanoassemblies offer an alternative to settle the deficiencies of traditional chemotherapy drugs. In this nanosystem, prodrugs typically comprise drug modules, modification modules, and response modules. The response modules are crucial for facilitating the accurate conversion of prodrugs at specific sites. In this work, we opted for differentiated disulfide bonds as response modules to construct docetaxel (DTX) prodrug nanoassemblies. Interestingly, a subtle change in response modules leads to a "U-shaped" conversion rate of DTX-prodrug nanoassemblies. Prodrug nanoassemblies with the least carbon numbers between the disulfide bond and ester bond (PDONα) offered the fastest conversion rate, resulting in powerful treatment outcomes with some unavoidable toxic effects. PDONß, with more carbon numbers, possessed a slow conversion rate and poor antitumor efficacy but good tolerance. With most carbon numbers in PDONγ, it demonstrated a moderate conversion rate and antitumor effect but induced a risk of lethality. Our study explored the function of response modules and highlighted their importance in prodrug development.

DHA and EPA inhibit porcine coronavirus replication by alleviating ER stress.

IMPORTANCE: Porcine epidemic diarrhea caused by porcine coronaviruses remains a major threat to the global swine industry. Fatty acids are extensively involved in the whole life of the virus. In this study, we found that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) significantly reduced the viral load of porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine delta coronavirus (PDCoV) and acted on the replication of the viruses rather than attachment and entry. We further confirmed that DHA and EPA inhibited PEDV replication by alleviating the endoplasmic reticulum stress. Meanwhile, DHA and EPA alleviate PEDV-induced inflammation and reactive oxygen species (ROS) levels and enhance the cellular antioxidant capacity. These data indicate that DHA and EPA have antiviral effects on porcine coronaviruses and provide a molecular basis for the development of new fatty acid-based therapies to control porcine coronavirus infection and transmission.

Rational Engineering Docetaxel Prodrug Nanoassemblies: Response Modules Guiding Efficacy Enhancement and Toxicity Reduction.

Prodrug-based nanoassemblies have been developed to solve the bottlenecks of chemotherapeutic drugs. The fabricated prodrugs usually consist of active drug modules, response modules, and modification modules. Among three modules, the response modules play a vital role in controlling the intelligent drug release at tumor sites. Herein, various locations of disulfide bond linkages were selected as response modules to construct three Docetaxel (DTX) prodrugs. Interestingly, the small structural difference caused by the length of response modules endowed corresponding prodrug nanoassemblies with unique characteristic. α-DTX-OD nanoparticles (NPs) possessed the advantages of high redox-responsiveness due to their shortest linkages. However, they were too sensitive to retain the intact structure in the blood circulation, leading to severe systematic toxicity. ß-DTX-OD NPs significantly improved the pharmacokinetics of DTX but may induce damage to the liver. In comparison, γ-DTX-OD NPs with the longest linkages greatly ameliorated the delivery efficiency of DTX as well as improved DTX's tolerance dose.

Effects of konjac glucomannan/pomegranate peel extract composite coating on the quality and nutritional properties of fresh-cut kiwifruit and green bell pepper.

The effects of an edible coating, based on konjac glucomannan (KG) incorporated with pomegranate peel extracts (PE), on the physicochemical and nutritional properties of fresh-cut kiwifruit and green bell pepper during storage were investigated. The optimal extract time (40.6 min), temperature (54.5 °C), and ultrasound power (255.5 W) with response surface method, provided a high total antioxidant activity (TAA) of (92.31 ± 1.43)%. Fresh-cut kiwifruit and green bell pepper were coated by dipping using five treatments (distilled water, ascorbic acid, KG, PE, KG + PE), packed into polymeric film and stored for 8 days at 10 °C. Distilled water treatment was used as control. KG + PE treatment resulted in the highest total soluble solid and titratable acidity in fresh-cut kiwifruit, while the maximum firmness in fresh-cut green bell pepper. The weight loss was both effectively decreased in samples treated with KG or KG + PE. All samples treated with KG + PE had significantly higher contents of chlorophyll, ascorbic acid, total phenolic and TAA than others. Moreover, the KG + PE group had the lowest counts of microorganisms in all samples. KG coating incorporated with PE was proved to be efficient in maintaining the physico-chemical and nutritional properties of fresh-cut kiwifruit and green bell pepper during low temperature storage compared with control. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05006-7.

DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy.

Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H2O2-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H2O2 and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl4 and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.

Motor style at rest and during locomotion in human.

Humans exhibit various motor styles that reflect their intra- and interindividual variability when implementing sensorimotor transformations. This opens important questions, such as, At what point should they be readjusted to maintain optimal motor control? Do changes in motor style reveal the onset of a pathological process and can these changes help rehabilitation and recovery? To further investigate the concept of motor style, tests were carried out to quantify posture at rest and motor control in 18 healthy subjects under four conditions: walking at three velocities (comfortable walking, walking at 4 km/h, and race walking) and running at maximum velocity. The results suggest that motor control can be conveniently decomposed into a static component (a stable configuration of the head and column with respect to the gravitational vertical) and dynamic components (head, trunk, and limb movements) in humans, as in quadrupeds, and both at rest and during locomotion. These skeletal configurations provide static markers to quantify the motor style of individuals because they exhibit large variability among subjects. Also, using four measurements (jerk, root mean square, sample entropy, and the two-thirds power law), it was shown that the dynamics were variable at both intra- and interindividual levels during locomotion. Variability increased following a head-to -toe gradient. These findings led us to select dynamic markers that could define, together with static markers, the motor style of a subject. Finally, our results support the view that postural and motor control are subserved by different neuronal networks in frontal, sagittal, and transversal planes.NEW & NOTEWORTHY During human locomotion, motor control can be conveniently decomposed into a static and dynamic components. Variable dynamics were observed at both the intra- and interindividual levels during locomotion. Variability increased following a head-to-toe gradient. Finally, our results support the view that postural and motor control are subserved by different neuronal networks in the frontal, sagittal, and transversal planes.

Viscoelastic lyotropic liquid crystals formed in a bio-based trimeric surfactant system.

Exploring the self-assembly of oligomeric surfactants is expected to bridge the gap between conventional and polymeric surfactants. Using the natural resource rosin as the starting material, a bio-based star-shaped trimeric quaternary ammonium surfactant (abbreviated tri-R-4-Phe) was synthesized. With three bulky dehydroabietic acid units in the hydrophobic group, tri-R-4-Phe has a molecular weight of 1684.9 and shows strong affinity towards both water and nonpolar organic compounds. In the presence of tri-R-4-Phe, C12EO3 was able to form lamellar lyotropic liquid crystals over a wide concentration range in water. The tri-R-4-Phe/C12EO3/water tertiary system was investigated by polarizing optical microscopy (POM), small angle X-ray scattering (SAXS) and rheological measurements. The investigated samples with different formulations all showed strong viscoelasticity, and the viscosity increased with the surfactant content. All samples showed interesting shear banding phenomena due to the shear induced mesoscale phase transition in tri-R-4-Phe/C12EO3/water systems. The present work reveals the unique behaviour of trimeric surfactant involved LLC systems and the result may be helpful in investigating delicate molecular self-assembly using natural resources.

PLOD3 is Upregulated in Gastric Cancer and Correlated with Clinicopathologic Characteristics.

BACKGROUND: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) has been proven to be involved in various human cancers; however, the function of PLOD3 in gastric cancer (GC) remains unclear. In this study, the role of PLOD3 in GC was evaluated. METHODS: The expression of PLOD3 in GC tissues and normal tissues was predicted by The Cancer Genome Atlas (TCGA). The kmplot online tool was performed to evaluate the impact of PLOD3 expression on GC patients' survival. Real-time PCR was conducted to verify PLOD3 expression in our own clinical samples and GC cells. The Cell Counting Kit-8 and the colony formation assay were used to detect GC cell proliferation ability. RESULTS: PLOD3 was upregulated in human GC tissues (compared to adjacent normal tissues, p < 0.001) and GC cells. High expression of PLOD3 was significantly correlated with larger tumor size (p = 0.007) and poor prognosis. Inhibition of PLOD3 could suppress cell proliferation in GC. CONCLUSIONS: These results revealed that PLOD3 may promote the progression of GC.

Magnetic resonance imaging analysis of brain function in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional disease of the gastrointestinal tract. The current study aimed to examine the association between visceral hypersensitivity in IBS and cortical activation using functional magnetic resonance imaging (fMRI), and to elucidate the role of psychological factors in the pathogenesis of IBS. METHODS: The present study included 31 patients with IBS and 20 healthy controls. Cerebral function was assessed using fMRI. During imaging, a Sengstaken-Blakemore tube was placed within the rectum approximately 10 cm from the anus, following which gas was rapidly injected into the airbag using a 150-ml syringe. Images were obtained at 40 ml, 80 ml, and 120 ml of expansion. Psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Anxiety and depression scores were higher among patients with IBSthan among controls (both P < 0.05), although scores in both groups were below the level of clinical diagnosis. Brain activation in regions of interest (parietal areas, prefrontal cortex, cerebellum, anterior cingulate cortex, insular cortex, and thalamus) increased along with increases in rectal balloon dilation, except in women with IBS and patients with disease duration less than 5 years. Furthermore, region of interest (ROI) activation (such as the parietal region, prefrontal cortex, cerebellum, anterior cingulate cortex, insular cortex, and thalamus) differed significantly between the 40-ml and 120-ml conditions, and between the 80-ml and 120-ml conditions (P < 0.05), among patients with IBS with anxiety or depression scores less than 9 points. CONCLUSIONS: Overall, our findings indicate that changes in brain activation due to changes in rectal balloon distension can be objectively and accurately measured using fMRI. Although our results indicated that visceral hypersensitivity during IBS is associated with changes in cortical activation, further studies utilizing larger sample sizes are required to more fully elucidate the association between psychological factors and visceral hypersensitivity in IBS.

Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: a monocentric cohort study in China.

BACKGROUND: The search for better non-invasive biomarkers for gastric cancer remains ongoing. We investigated the predictive power of serum trefoil factor (TFF) levels as biomarkers for gastric cancer in comparison with the pepsinogen (PG) test. METHODS: Patients with gastric cancer, chronic atrophic gastritis (CAG) or chronic non-atrophic gastritis (CNAG), and healthy people were recruited. Serum concentrations of TFFs, PG I, and PG II, as well as the presence of antibodies against Helicobacter pylori, were measured by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristics (ROC) were used to compare the predictive powers of the selected factors. RESULTS: The serum concentrations of TFF1, TFF2, and TFF3 in the control groups were significantly lower than those in the gastric cancer group with the exception of TFF2 which was elevated in CAG. The area under the ROC curve for TFF3 was greater than that for the PG I/II ratio (0.81 vs 0.78). TFF3 also had a significantly higher predictive power for distinguishing gastric cancer than the PG test (odds ratio: 10.33 vs 2.57). Moreover, combining the serum TFF3 and PG tests for gastric cancer had better predictive power than either alone. CONCLUSIONS: Serum TFF3 may be a better predictor of gastric cancer than the PG test, while the combined testing of serum PG and TFF3 could further improve the efficacy of gastric cancer screening.

Investigation of morphology and structure of drug-loaded PLA-b-PEO-b-PLA polymeric micelle: A dissipative particle dynamics simulations study.

The dissipative particle dynamics (DPD) simulation was used to study the morphologies and structures of the paclitaxel-loaded PLA-b-PEO-b-PLA polymeric micelle. We focused on the influences of PLA block length, PLA-b-PEO-b-PLA copolymer concentration, paclitaxel drug content on morphologies and structures of the micelle. Our simulations show that: (i) with the PLA block length increase, the self-assemble structure of PLA-b-PEO-b-PLA copolymers with paclitaxel vary between onion-like structure (core-middle layer-shell) to spherical core-shell structure. The PEO shell thins and the size of the PLA core increases. The onionlike structures are comprised of the PEO hydrophilic core, the PLA hydrophobic middle layer, and the PEO hydrophilic shell, the distribution of the paclitaxel drug predominantly occurs within the hydrophobic intermediate layer; (ii) The system forms a spherical core-shell structure when a small amount of the drug is added, and within a certain range, the size of the spherical structure increases as the drug amount increases. When the drug contents (volume fraction) cdrug = 10%, it can be observed that the PLA4-b-PEO19-b-PLA4 spherical structures connect to form rod-shaped structures. With the length of PLA block NPLA = 8, as the paclitaxel drug concentrations cdrug = 4%, PEO has been insufficient to completely encapsulate the PLA and paclitaxel drug beads. To enhance drug loading capacity while maintaining stability of the system in aqueous solution, the optimal composition for loading paclitaxel is PLA4-b-PEO19-b-PLA4; the drug content is not higher than 4%; (iii) The paclitaxel-loaded PLA4-b-PEO19-b-PLA4 micelle undergo the transition from onionlike (core-middle layer-shell) to spherical (core-shell) to rod-shaped and lamellar structure as the PLA4-b-PEO19-b-PLA4 copolymer concentration increases from ccp = 10% to 40%.

Case report: A novel perspective on the treatment of primary tracheal small cell carcinoma: a patient's experience with immuno-combined EP therapy and literature review.

Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the therapeutic guidelines established for small cell lung cancer, although numerous unresolved issues remain. This paper details a case study of a patient with Stage IIIB primary tracheal SCC, who was treated with an immune-combined etoposide-platinum(EP) regimen. This treatment offers valuable insights into innovative approaches for managing such malignancies. Furthermore, the study includes a comprehensive literature review to better contextualize the findings. The patient, admitted on May 2, 2023, had been experiencing persistent symptoms of airway discomfort for 15 days. A bronchoscopy performed on May 4 revealed tracheal SCC, classified as T4N2M0, IIIB. Following the CAPSTONE-1 study's methodology, the patient underwent six cycles of PD-L1(adebrelimab) combined with EP therapy, leading to significant relief of symptoms and the eventual disappearance of the tracheal mass.

Grouped Multivariate Variational Mode Decomposition With Application to EEG Analysis.

OBJECTIVE: In this paper, a novel extended form of multivariate variational mode decomposition (MVMD) method to multigroup data named as grouped MVMD (GMVMD) is proposed. GMVMD is distinct from MVMD as it extracts common frequencies with strong correlations among regional channels. METHODS: Firstly, GMVMD utilizes a new clustering algorithm named as frequencies grouping algorithm to classify the nearest common frequencies among all channels to specified groups. Secondly, a generic variational optimization model which is extended from MVMD is formulated. Thirdly, alternating direction method of multipliers (ADMM) is utilized to obtain optimal solution of GMVMD model. RESULTS: The proposed method introduces an extra parameter to decide the number of clusterings which need to be specified by the user. The effectiveness and superiority of the algorithm are demonstrated on a series of experiments. The utility of GMVMD is verified by grouping real-world electroencephalogram (EEG) data having similar center frequencies successfully. CONCLUSION: GMVMD outperforms MVMD in mode-alignment, signal reduction error and et al. Significance: GMVMD can obtain more accurate center frequencies and less signal reduction error than MVMD.

Satellite-Type Sulfur Atom Distribution in Trithiocarbonate Bond-Bridged Dimeric Prodrug Nanoassemblies: Achieving Both Stability and Activatability.

Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo-drugs. However, the key challenge lies in designing rational chemical linkers that can simultaneously ensure the chemical stability, self-assembly stability, and site-specific activation of prodrugs. The "in series" increase in sulfur atoms, such as trisulfide bond, can improve the assembly stability of HDPNs to a certain extent, but limits the chemical stability of prodrugs. Herein, trithiocarbonate bond (─SC(S)S─), with a stable "satellite-type" distribution of sulfur atoms, is developed via the insertion of a central carbon atom in trisulfide bonds. ─SC(S)S─ bond effectively addresses the existing predicament of HDPNs by improving the chemical and self-assembly stability of homodimeric prodrugs while maintaining the on-demand bioactivation. Furthermore, ─SC(S)S─ bond inhibits antioxidant defense system, leading to up-regulation of the cellular ROS and apoptosis of tumor cells. These improvements of ─SC(S)S─ bond endow the HDPNs with in vivo longevity and tumor specificity, ultimately enhancing the therapeutic outcomes. ─SC(S)S─ bond is, therefore, promising for overcoming the bottleneck of HDPNs for efficient oncological therapy.

The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies.

The self-assembly prodrugs are usually consisted of drug modules, activation modules, and assembly modules. Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies. This study designed four docetaxel (DTX) prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules (C16, C18, C20, and C24). The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules' sensitivity. The extension of the carbon chains improved the prodrugs' self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity. The use of C20 can balance efficacy and safety. These results provide a great reference for the rational design of prodrug nanoassemblies.

Global and multi-partition local network analysis of scalp EEG in West syndrome before and after treatment.

West syndrome is an epileptic disease that seriously affects the normal growth and development of infants in early childhood. Based on the methods of brain topological network and graph theory, this article focuses on three clinical states of patients before and after treatment. In addition to discussing bidirectional and unidirectional global networks from the perspective of computational principles, a more in-depth analysis of local intra-network and inter-network characteristics of multi-partitioned networks is also performed. The spatial feature distribution based on feature path length is introduced for the first time. The results show that the bidirectional network has better significant differentiation. The rhythmic feature change trend and spatial characteristic distribution of this network can be used as a measure of the impact on global information processing in the brain after treatment. And localized brain regions variability in features and differences in the ability to interact with information between brain regions have potential as biomarkers for medication assessment in WEST syndrome. The above shows specific conclusions on the interaction relationship and consistency of macro-network and micro-network, which may have a positive effect on patients' treatment and prognosis management.

Exploring the optimal chain length of modification module in disulfide bond bridged paclitaxel prodrug nanoassemblies for breast tumor treatment.

In the prodrug-based self-assembled nanoassemblies, prodrugs usually consist of drug modules, response modules, and modification modules. Modification modules play a critical role in regulating the nano-assembly ability of the prodrugs. Herein, we carried out a "fatty alcoholization" strategy and chose various lengths of aliphatic alcohol chains (AC) as modification modules to construct disulfide bond bridged paclitaxel (PTX) prodrug nanoassemblies. The PTX-AC prodrugs would self-assemble into nanoassemblies (PTX-AC PNs) with higher drug loading, stability, and tumor selectivity than commercial preparations. After comprehensive exploration, we found the chain length (AC12, AC16, AC20, AC24) of modification modules affected the assembly of PTX-AC PNs, further leading to disparate in vivo fate and antitumor efficacy. With the increase of the chain length of the modification modules (from AC12 to AC20), the assembly ability of the nanoassemblies was improved, attributed to the appropriate enhancement of hydrophobic force. When the chain length was further increased to AC24, the excessive hydrophobic force will lead to the aggregation of prodrugs and weaken the assembly ability. Therefore, PTX-AC20 PNs with proper chain length may solve the paradox of efficacy and tolerance in 4 T1 breast tumor owing to their optimal nano-assembly stability and modest redox-sensitivity. In short, this work highlighted the importance of screening optimal modification modules in developing prodrug nanoassemblies.

Grit in second language acquisition: a systematic review from 2017 to 2022.

Recent years have witnessed increasing attention to personality strength (grit) due to its merit in goal-seeking language learning processes. Two facets of grit, namely perseverance of effort (PE) and consistency of interest (CI), play a critical role in overcoming learning difficulties and strengthening willpower to pursue learning goals. The current review seeks to explore various issues related to grit, including its factor structure, the relationship between grit and frequently associated factors, as well as the utility of PE and CI in facilitating language learning. This exploration is based on the findings of 32 empirical articles published between 2017 and 2022 from three databases. The results indicate that although research which examines the role of grit has entered a fast growth phase since 2020, there is still a need for expansion and diversification in scopes, participants, research methods, and language contexts. Moreover, previous studies have not adequately addressed the critical issue of grit's conceptualization and factor structure. Finally, this study suggests that future researchers should impartially assess the factor structure and nature of PE and CI, to provide more robust evidence to clarify the relationship between grit and diverse emotions and positive institutions, in order to advance understanding of grit in second language learning.

Becoming a Non-native Chinese Language Teacher: An Identity Triangle Model Analysis.

This study utilises the Identity Triangle Model (Dugas in Teach Dev 25(3):243-262, 2021, 10.1080/13664530.2021.1874500) to examine the experiences of one particular novice non-native Mandarin Chinese teacher at a university in New Zealand. A case study design was employed to track the identity negotiations of this European non-native Chinese speaker during 12 weeks of her first semester of teaching. Analysis of the data revealed nine subcategories within the psychological, behavioural, and relational domains according to the Identity Triangle Model. The findings suggest that this new non-native speaker teacher viewed her as an accidental teacher, exploring a teaching career without a strong instrumentalist aspiration or a clear career path in language teaching. Instead, she was more motivated by a desire for personal growth and the opportunity to reinvent themselves in a new cultural context. The results of this study offer theoretical implications for the adoption of a unified framework in future research on the identity of first-time language teachers, and practical implications for developing sustainable strategies aimed at recruiting and retaining non-native speaker teachers in foreign language education.

[Retracted] MicroRNA­616 promotes the growth and metastasis of non­small cell lung cancer by targeting SOX7.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cell formation assay data shown in Figs. 3D, 4D, 8D and 9D were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Wang Z, Jiang C, Chen W, Zhang G, Luo D, Cao Y Wu J, Ding Y and Liu B: Baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma. Biomed Res Int: 732516, 2014]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 2078­2086, 2017; DOI: 10.3892/or.2017.5854].