Modulus alteration of thin polystyrene films by their neighboring PDMS: Soft and hard confinement.

It is highly demanded to understand the confinement effect on nanoconfined polymers. Recent studies reported a strong perturbation of local dynamics and substantial alteration of glass transition temperature Tg at nanoscale. However, how confinement affects the mechanical properties of polymers is not fully understood. Here, we show that the modulus of thin polymer films could be remarkedly altered through a polymer-polymer interface. The modulus of a thin polystyrene (PS) film next to a polydimethylsiloxane (PDMS) was determined from the PS-PDMS bilayer bulging test. A series of experiments show that the modulus of PS can be increased up to 37%, when the modulus of the neighboring PDMS varies from 1.04 to 4.88 MPa. The results demonstrate a strong sensitivity of mechanical properties of thin polymers to the hard/soft environment, which we attribute to the change of high-mobility layer by the polymer-polymer interface.

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications - review article.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.

KNSTRN Is a Prognostic Biomarker That Is Correlated with Immune Infiltration in Breast Cancer and Promotes Cell Cycle and Proliferation.

Kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) promotes the progression of bladder cancer and lung adenocarcinoma. However, its expression and biological function in breast cancer remain largely unknown. Therefore, this study aimed to analyze KNSTRN expression, prognoses, correlation with immune infiltration, expression-associated genes, and regulated signaling pathways to characterize its role in regulating the cell cycle using both bioinformatics and in vitro functional experiments. Analyses of The Cancer Genome Atlas, Gene Expression Omnibus, TIMER, and The Human Protein Atlas databases revealed a significant upregulation of KNSTRN transcript and protein levels in breast cancer. Kaplan-Meier survival analyses demonstrated a significant association between high expression of KNSTRN and poor overall survival, relapse-free survival, post-progression survival, and distant metastases-free survival in patients with breast cancer. Furthermore, multivariate Cox regression analyses confirmed that KNSTRN is an independent prognostic factor for breast cancer. Immune infiltration analysis indicated a positive correlation between KNSTRN expression and T regulatory cell infiltration while showing a negative correlation with Tgd and natural killer cell infiltration. Gene set enrichment analysis along with single-cell transcriptome data analysis suggested that KNSTRN promoted cell cycle progression by regulating the expression of key cell cycle proteins. The overexpression and silencing of KNSTRN in vitro, respectively, promoted and inhibited the proliferation of breast cancer cells. The overexpression of KNSTRN enhanced the expression of key cell cycle regulators, including CDK4, CDK6, and cyclin D3, thereby accelerating the G1/S phase transition and leading to aberrant proliferation of breast cancer cells. In conclusion, our study demonstrates that KNSTRN functions as an oncogene in breast cancer by regulating immune response, promoting G1/S transition, and facilitating breast cancer cell proliferation. Moreover, KNSTRN has potential as a molecular biomarker for diagnostic and prognostic prediction in breast cancer.

Roles of PPAR activation in cancer therapeutic resistance: Implications for combination therapy and drug development.

Therapeutic resistance is a major obstacle to successful treatment or effective containment of cancer. Peroxisome proliferator-activated receptors (PPARs) play an essential role in regulating energy homeostasis and determining cell fate. Despite of the pleiotropic roles of PPARs in cancer, numerous studies have suggested their intricate relationship with therapeutic resistance in cancer. In this review, we provided an overview of the roles of excessively activated PPARs in promoting resistance to modern anti-cancer treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The mechanisms through which activated PPARs contribute to therapeutic resistance in most cases include metabolic reprogramming, anti-oxidant defense, anti-apoptosis signaling, proliferation-promoting pathways, and induction of an immunosuppressive tumor microenvironment. In addition, we discussed the mechanisms through which activated PPARs lead to multidrug resistance in cancer, including drug efflux, epithelial-to-mesenchymal transition, and acquisition and maintenance of the cancer stem cell phenotype. Preliminary studies investigating the effect of combination therapies with PPAR antagonists have suggested the potential of these antagonists in reversing resistance and facilitating sustained cancer management. These findings will provide a valuable reference for further research on and clinical translation of PPAR-targeting treatment strategies.

Direct measurement and modeling of viscoelastic-viscoplastic properties of freely standing thin polystyrene films.

The demand for applications, such as coatings, separation filters, and electronic packaging, has greatly driven the research of polymer films. At nanometer scale, mechanical properties of thin polymer films can significantly deviate from bulk. Despite outstanding progresses, there still lack deep discussions on nonlinear viscoelastic-viscoplastic response and their interactions under nanoconfinement. In this work, by conducting measurements via the bubble inflation method and modelling using Schapery and Perzyna equations, we demonstrate nonlinear viscoelastic-viscoplastic properties of freely standing thin polystyrene (PS) films. The results show the unchanged glassy compliance and the rubbery stiffening phenomenon for thin PS films, where the lower rubbery plateau in rubbery stiffening may originate from the induced molecular orientation by plastic deformation. With decreasing film thickness, viscosity and yield stress in viscoplasticity increase in an exponential and a linear trend, respectively, indicating the significant role of nanoconfinement effect on viscoplastic properties. These findings may reveal that there are many properties from linear viscoelasticity to nonlinear viscoelasticity-viscoplasticity that need to be explored and unveiled for sufficient understanding of the nanoconfinement effect on altering mechanical behavior of polymers.

Focal ablation therapy presents promising results for selectively localized prostate cancer patients.

Due to its lower risk of consequences when compared to a radical approach, focal treatment is a viable and minimally invasive option for treating specific localized prostate cancer. Although several recent good non-randomized trials have suggested that focused therapy may be an alternative choice for some patients, additional high-quality evidence is needed before it can be made widely available as a conventional treatment. As a result, we have summarized the most recent findings from the 38th Annual European Association of Urology Congress, one of the most renowned annual conferences in the area of urology, regarding focal ablation therapy for patients with localized prostate cancer. Additionally, we also provided clinical trials in progress for researchers to better understand the current research status of this field.

Surface plasmonic coupling of Au nanoparticle arrays with ultrathin hexagonal boron nitride nanosheets for Raman enhancement.

Integration of hexagonal boron nitride (h-BN) with plasmonic nanostructures that possess nanoscale field confinement will enable unusual properties; hence, the manipulation and understanding of the light interactions are highly desirable. Here, we demonstrate the surface plasmonic coupling of Au nanoparticles (ANPs) with ultrathin h-BN nanosheets (BNNS) in nonspecific nanocomposites leading to a great enhancement of the Raman signal of E2g in both experimental and theoretical manner. The nanocomposites were fabricated from liquid-exfoliated atomically thin BNNS and diblock copolymer-based ANPs with excellent dispersion through a self-assembly approach. By precisely varying the size of ANPs from 3 to 9 nm, the Raman signal of BNNS was improved from 1.7 to 71. In addition, the underlying mechanism has been explored from the aspects of electromagnetic field coupling strength between the localized surface plasmons excited from ANPs and the surrounding dielectric h-BN layers, as well as the charge transfer at the BNNS/ANPs interfaces. Moreover, we also demonstrate its capability to detect dye molecules as a surface enhanced Raman scattering (SERS) substrate. This work provides a basis for the self-assembly of BNNS hierarchical nanocomposites allowing for plasmon-mediated modulation of their optoelectronic properties, thereby showing the great potential not only in the field of SERS but also in large-scale h-BN-based plasmonic devices.

Non-convulsive Status Epilepticus in SEMA6B-Related Progressive Myoclonic Epilepsy: A Case Report With Literature Review.

Progressive myoclonic epilepsy (PME) is a group of rare diseases characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. PME has high genetic heterogeneity, and more than 40 genes are reportedly associated with this disorder. SEMA6B encodes a member of the semaphorin family and was first reported to cause PME in 2020. Herein, we present a rare case of PME due to a novel SEMA6B gene mutation in a 6-year-old boy born to healthy non-consanguineous Chinese parents. His developmental milestones were delayed, and he developed recurrent atonic seizures and myoclonic seizures without fever at 3 years and 11 months of age. He experienced recurrent myoclonic seizures, non-convulsive status epilepticus (NCSE), atonic seizures, and atypical absence seizures during the last 2 years. At different time points since onset, valproic acid, levetiracetam, piracetam, and clobazam were used to control the intractable seizures. Notably, NCSE was controlled by a combination of piracetam with clobazam and valproic acid instead of intravenous infusion of midazolam and phenobarbital. Due to the limited number of cases reported to date, the clinical description of our case provides a better understanding of the genotype-phenotype correlations associated with PME and indicate that piracetam may be effective against NCSE in patients with SEMA6B-related PME.

A micro-vibration apparatus for dynamic mechanical analysis of ultrathin polymer films.

We present the design and validation of an apparatus, which is developed based on micro-vibration in cyclic bulge and contraction, to determine dynamic mechanical properties of ultrathin polymer films. By controlling air pressure acting on a polymer membrane, the apparatus exerts simple harmonic or other type periodic stresses on the film, and the resultant real-time deformation of the freely standing film is recorded by using a high-speed CCD camera. From the image frame sequences and the gas pressure data, the real-time stress and strain of the polymer film are attained. Consequently, the dynamic mechanical properties, including biaxial storage and loss moduli, and loss factor can be determined for polymer films with thickness down to 20 nm. This apparatus could also be used to determine other mechanical properties such as fatigue and yield for nanoconfined films of soft matter.

Estimating the Long-Term Epidemiological Trends and Seasonality of Hemorrhagic Fever with Renal Syndrome in China.

OBJECTIVE: We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS). METHODS: The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA). RESULTS: The TBATS (0.27, {0,0}, -, {<12,4>}) and SARIMA (0,1,(1,3))(0,1,1)12 were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May-June and November-December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=-6.767, 95% confidence intervals: -10.592 to -2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years. CONCLUSION: The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios.

Transcription factor MoMsn2 targets the putative 3-methylglutaconyl-CoA hydratase-encoding gene MoAUH1 to govern infectious growth via mitochondrial fusion/fission balance in Magnaporthe oryzae.

Mitochondrial quality and quantity are essential for a cell to maintain normal cellular functions. Our previous study revealed that the transcription factor MoMsn2 plays important roles in the development and virulence of Magnaporthe oryzae. However, to date, no study has reported its underlying regulatory mechanism in phytopathogens. Here, we explored the downstream target genes of MoMsn2 using a chromatin immunoprecipitation sequencing (ChIP-Seq) approach. In total, 332 target genes and five putative MoMsn2-binding sites were identified. The 332 genes exhibited a diverse array of functions and the highly represented were genes involved in metabolic and catalytic processes. Based on the ChIP-Seq data, we found that MoMsn2 plays a role in maintaining mitochondrial morphology, likely by targeting a number of mitochondria-related genes. Further investigation revealed that MoMsn2 targets the putative 3-methylglutaconyl-CoA hydratase-encoding gene (MoAUH1) to control mitochondrial morphology and mitophagy, which are critical for the infectious growth of the pathogen. Meanwhile, the deletion of MoAUH1 resulted in phenotypes similar to the ΔMomsn2 mutant in mitochondrial morphology, mitophagy and virulence. Overall, our results provide evidence for the regulatory mechanisms of MoMsn2, which targets MoAUH1 to modulate its transcript levels, thereby disturbing the mitochondrial fusion/fission balance. This ultimately affects the development and virulence of M. oryzae.

Status Epilepticus Manifested as Continuous Epileptic Spasms.

Objective: The etiology and outcome of status epilepticus with continuous epileptic spasms have not been fully understood; and only rare cases have been reported in the literature. Here, we described 11 children, who manifested continuous epileptic spasms with various etiologies and different outcomes. Methods: This is a case series study designed to systematically review the charts, video-electroencephalography (video-EEG), magnetic resonance images, and longitudinal follow-up of patients who presented continuous epileptic spasms lasting more than 30 min. Results: Median age at onset was 2 years old, ranging from 2 months to 5.6 years. The etiology of continuous epileptic spasms for these 11 cases consisted of not only some known electro-clinical epilepsy syndromes like West Syndrome and Ohtahara Syndrome, but also secondary symptomatic continuous epileptic spasms, caused by acute encephalitis or encephalopathy, which extends the etiological spectrum of continuous epileptic spasms. The most characteristic feature of these 11 cases was prolonged epileptic spasms, lasting for a median of 13.00 days (95% CI: 7.26-128.22 days). The interictal EEG findings typically manifested as hypsarrhythmia or its variants, including burst suppression. Hospital stays were much longer in acute symptomatic cases than in primary epileptic syndromic cases (59.67 ± 50.82 vs. 15.00 ± 1.41 days). However, the long-term outcomes were extremely poor in the patients with defined electro-clinical epilepsy syndromes, including severe motor and intellectual developmental deficits (follow-up of 4.94 ± 1.56 years), despite early diagnosis and treatment. Continuous epileptic spasms were refractory to corticosteroids, immuno-modulation or immunosuppressive therapies, and ketogenic diet. Conclusion: Continuous epileptic spasms were associated with severe brain impairments in patients with electro-clinical syndromes; and required long hospital stays in patients with acute symptomatic causes. We suggest to include continuous epileptic spasms in the international classification of status epilepticus, as a special form. Further investigations are required to better recognize this condition, better understand the etiology, as well as to explore more effective treatments to improve outcomes.