Diverse drug delivery systems for the enhancement of cancer immunotherapy: an overview

Despite the clear benefits demonstrated by immunotherapy, there is still an inevitable off-target effect resulting in serious adverse immune reactions. In recent years, the research and development of Drug Delivery System (DDS) has received increased prominence. In decades of development, DDS has demonstrated the ability to deliver drugs in a precisely targeted manner to mitigate side effects and has the advantages of flexible control of drug release, improved pharmacokinetics, and drug distribution. Therefore, we consider that combining cancer immunotherapy with DDS can enhance the anti-tumor ability. In this paper, we provide an overview of the latest drug delivery strategies in cancer immunotherapy and briefly introduce the characteristics of DDS based on nano-carriers (liposomes, polymer nano-micelles, mesoporous silica, extracellular vesicles, etc.) and coupling technology (ADCs, PDCs and targeted protein degradation). Our aim is to show readers a variety of drug delivery platforms under different immune mechanisms, and analyze their advantages and limitations, to provide more superior and accurate targeting strategies for cancer immunotherapy

Pseudogap, Superconducting Energy Scale, and Fermi Arcs in Underdoped Cuprate Superconductors

Through the measurements of magnetic field dependence of specific heat in $La_{2-x}Sr_xCuO_4$ in zero temperature limit, we determined the nodal slope $v_\Delta$ of the quasiparticle gap. It is found that $v_\Delta$ has a very similar doping dependence of the pseudogap temperature $T^*$ or value $\Delta_p$. Meanwhile the virtual maximum gap at ($\pi,0$) derived from $v_\Delta$ is found to follow the simple relation $\Delta_q=0.46k_BT^*$ upon changing the doping concentration. This strongly suggests a close relationship between the pseudogap and superconductivity. It is further found that the superconducting transition temperature is determined by both the residual density of states of the pseudogap phase and the nodal gap slope in the zero temperature limit, namely, $T_c \approx \beta v_\Delta \gamma_n(0)$, where $\gamma_n(0)$ is the extracted zero temperature value of the normal state specific heat coefficient which is proportional to the size of the residual Fermi arc $k_{arc}$. This manifests that the superconductivity may be formed by forming a new gap on the Fermi arcs near nodes below $T_c$. These observations mimic the key predictions of the SU(2) slave boson theory based on the general resonating-valence-bond (RVB) picture.Comment: 6 pages, 6 figures, to be published in Phys. Rev.

Fiber Optical Tweezers for Applying and Measuring Forces in a 3D Solid Compartment

We developed an inclined dual fiber optical tweezers (DFOTs) for simultaneous force application and measurements in a 3D hydrogel matrix. The inclined DFOTs provide a potential solution for cell mechanics study in a three-dimensional matrix

2-[(1,3-Benzothia­zol-2-yl)imino­meth­yl]-4-bromo­phenol

In the title compound, C14H9BrN2OS, the dihedral angle between the benzene rings is 3.1 (3)°. An intra­molecular O—H⋯N(imine) hydrogen bond occurs. The crystal structure is stabilized by weak inter­molecular C—H⋯O inter­actions

Coarse-Super-Resolution-Fine Network (CoSF-Net): A Unified End-to-End Neural Network for 4D-MRI with Simultaneous Motion Estimation and Super-Resolution

Four-dimensional magnetic resonance imaging (4D-MRI) is an emerging technique for tumor motion management in image-guided radiation therapy (IGRT). However, current 4D-MRI suffers from low spatial resolution and strong motion artifacts owing to the long acquisition time and patients' respiratory variations; these limitations, if not managed properly, can adversely affect treatment planning and delivery in IGRT. Herein, we developed a novel deep learning framework called the coarse-super-resolution-fine network (CoSF-Net) to achieve simultaneous motion estimation and super-resolution in a unified model. We designed CoSF-Net by fully excavating the inherent properties of 4D-MRI, with consideration of limited and imperfectly matched training datasets. We conducted extensive experiments on multiple real patient datasets to verify the feasibility and robustness of the developed network. Compared with existing networks and three state-of-the-art conventional algorithms, CoSF-Net not only accurately estimated the deformable vector fields between the respiratory phases of 4D-MRI but also simultaneously improved the spatial resolution of 4D-MRI with enhanced anatomic features, yielding 4D-MR images with high spatiotemporal resolution

Electronic specific heat and low energy quasiparticle excitations in superconducting state of La2−xSrxCuO4La_{2-x}Sr_xCuO_4 single crystals

Low temperature specific heat has been measured and extensively analyzed on a series of $La_{2-x}Sr_xCuO_4$ single crystals from underdoped to overdoped regime. From these data the quasiparticle density of states (DOS) in the mixed state is derived and compared to the predicted scaling law $C_{vol}/T\sqrt{H}=f(T/\sqrt{H})$ of d-wave superconductivity. It is found that the scaling law can be nicely followed by the optimally doped sample (x=0.15) in quite wide region of ($T/\sqrt{H} \leq 8 K /\sqrt{T}$). However, the region for this scaling becomes smaller and smaller towards more underdoped region: a clear trend can be seen for samples from x=0.15 to 0.069. Therefore, generally speaking, the scaling quality becomes worse on the underdoped samples in terms of scalable region of $T/\sqrt{H}$. This feature in the underdoped region is explained as due to the low energy excitations from a second order (for example, anti-ferromagnetic correlation, d-density wave, spin density wave or charge density wave order) that may co-exist or compete with superconductivity. Surprisingly, deviations from the d-wave scaling law have also been found for the overdoped sample (x=0.22). While the scaling law is reconciled for the overdoped sample when the core size effect is taken into account. An important discovery of present work is that the zero-temperature data follow the Volovik's relation $\Delta \gamma(T=0)=A\sqrt{H}$ quite well for all samples investigated here although the applicability of the d-wave scaling law to the data at finite temperatures varies with doped hole concentration. Finally we present the doping dependence of some parameters, such as, the residual linear term $\gamma_0$, the $\alpha$ value, etc. ...Comment: 15 pages, 24 figure

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current