Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

Prostate cancer is one of the most common types of cancer affecting men worldwide; however, its etiology and pathological mechanisms remain poorly understood. Mechanical stimulation plays a key role in prostate cancer development. Piezo type mechanosensitive ion channel component 1 (Piezo1), which functions as a cell sensor and transducer of mechanical stimuli, may have a crucial role in the development of prostate cancer. In the present study, the expression of the Piezo1 channel was demonstrated to be significantly elevated in prostate cancer cell lines and in human prostate malignant tumor tissues. Downregulation of Piezo1 significantly suppressed the viability, proliferation and migration of prostate cancer cells in vitro , and inhibited prostate tumor growth in vivo . The activation of the Akt/mTOR pathway or acceleration of cell cycle progression from G 0 /G 1 to S phase may downstream consequences of Piezo 1 signal pathway activation. Downregulation of Piezo1 considerably suppressed Ca 2+ signal increments, inhibited the phosphorylation of Akt and mTOR and arrested the cell cycle of prostate cancer cells at G 0 /G 1 phase in while inhibiting the activation of CDK4 and cyclin D1. Taken together, these findings suggest that Piezo1 channels have a crucial role in prostate cancer development and may, therefore, be a novel therapeutic target in the treatment of prostate cancer.

We study both the static properties and dynamic behavior of liquid water marbles coated with silica nanoparticles of varied hydrophobicity. The static properties are characterized by the variation of marble height and diameter with increasing marble volume, such that the effective surface tension g eff of the marble can be obtained. The dynamic behavior of liquid marbles includes their impingement on a solid surface and their compression between two parallel glass plates. Marbles coated with particles of intermediate hydrophobicity exhibit maximum g eff values and enhanced mechanical robustness. Due to particle detachment from or particle rearrangement at the air-water interface caused by the impact, the dynamic surface tensions g d of liquid water marbles are different in magnitude to those of g eff . In fact, g d plays an important role in determining the contact time and oscillation period during the impact and rebound processes. Our results show that both the static effective and dynamic surface tension depend on the hydrophobicity of the particles coating the marble surfaces.

Manipulating the interfacial structure is vital to enhancing the interfacial thermal conductance (G) in Cu/diamond composites for promising thermal management applications. An interconnected interlayer is frequently observed in Cu/diamond composites; however, the G between Cu and diamond with an interconnected interlayer has not been addressed so far and thus is attracting extensive attention in the field. In this study, we designed three kinds of interlayers between a Cu film and a diamond substrate by magnetron sputtering coupled with heat treatment, including a W interlayer, an interconnected W–W2C interlayer, and a W2C interlayer, to comparatively elucidate the relationship between the interfacial structure and the interfacial thermal conductance. For the first time, we experimentally measured the G between Cu and diamond with an interconnected interlayer by a time-domain thermoreflectance technique. The Cu/W–W2C/diamond structure exhibits an intermediate G value of 25.8 MW/m2 K, higher than the 19.9 MW/m2 K value for the Cu/W2C/diamond structure and lower than the 29.4 MW/m2 K value for the Cu/W/diamond structure. The molecular dynamics simulations show that the G of the individual W2C/diamond interface is much higher than those of the individual Cu/diamond and W/diamond interfaces and W2C could reduce the vibrational mismatch between Cu and diamond; however, the G of the Cu/W2C/diamond structure is reduced by the lower thermal conductivity of W2C. This study provides insights into the relationship between the interconnected interfacial structure and the G between Cu and diamond and offers guidance for interface design to improve the thermal conductivity in Cu/diamond composites.

We investigate the impact dynamics of droplets containing silica nanoparticles and/or poly(ethylene oxide) (PEO) additives by using a high speed camera, and relate the impact behavior to the rheological properties of liquids. For a droplet with both particles and polymer additives, the rebound is damped much faster and the instability behavior is suppressed. Interestingly, the rebound can be inhibited even when impact is at high velocity (1.88 m s À1 ). The transition from ''rebound'' to ''stick'' by enhancing the impact velocity is mainly due to the increase of the friction force of the nanoparticles and polymer aggregates with the substrate. This is confirmed by the increase of the sliding angle with impact velocity.

The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na+ channels, and modulate their function. Mutations that affect iFGF/FHF-Na+ channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca2+ channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation. Patch clamp recordings from ventricular myocytes isolated from Fgf13 knockout mice showed a ~25% reduction in peak Na+ channel current density and a hyperpolarizing shift in steady-state inactivation. Electrocardiograms on Fgf13 knockout mice showed a prolonged QRS duration. The Na+ channel blocker flecainide further prolonged QRS duration and triggered ventricular tachyarrhythmias only in Fgf13 knockout mice, suggesting that arrhythmia vulnerability resulted, at least in part, from a loss of functioning Na+ channels. Consistent with these effects on Na+ channels, action potentials in Fgf13 knockout mice, compared to Cre control mice, exhibited slower upstrokes and reduced amplitude, but unexpectedly had longer durations. We investigated candidate sources of the prolonged action potential durations in myocytes from Fgf13 knockout mice and found a reduction of the transient outward K+ current (Ito). Fgf13 knockout did not alter whole-cell protein levels of Kv4.2 and Kv4.3, the Ito pore-forming subunits, but did decrease Kv4.2 and Kv4.3 at the sarcolemma. No changes were seen in the sustained outward K+ current or voltage-gated Ca2+ current, other candidate contributors to the increased action potential duration. These results implicate that FGF13 is a critical cardiac Na+ channel modulator and Fgf13 knockout mice have increased arrhythmia susceptibility in the setting of Na+ channel blockade. The unanticipated effect on Ito revealed new FGF13 properties and the unexpected lack of an effect on voltage-gated Ca2+ channels highlight potential compensatory changes in vivo not readily revealed with acute Fgf13 knockdown in cultured cardiomyocytes.

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The cracking behavior accompanied with the drying of colloidal droplets containing polytetrafluoroethylene (PTFE) nanoparticles was studied. During evaporation, due to the stretching effect of the liquid zone, the receding wet front leads to the formation of radialized surface wrinkling in the gel zone. This indicates the building of a macroscopic stress field with a similar distribution. As a result, the cracks in the deposited films are in a radial arrangement. The propagation velocity of the cracks depends on the thickness of the film, ∼ H (3/5). In addition, sodium dodecylsulfate (SDS) additives can be used to tune crack behavior by causing a reduction of the capillary force between particles. The results highlight the significance of the receding wet front in building the drying deposition stress field and may be helpful in other fields related to drying and cracking processes.