Efficacy and Safety of PD-1/PD-L1 Inhibitor and Chemotherapy in Treatment of Advanced Small Cell Lung Cancer.

Context: SCLC has had few drugs for treatment and a high malignancy rate. About two-thirds of SCLC patients have distant metastasis by the time they receive a diagnosis, and once it occurs, patient's survival time is short. Immunotherapy treatments can block immunosuppression and increase the body's antitumor ability. PD-1 is the main immune checkpoint of tumors' immune response, and PD-L1 is one of the ligands of PD-1. Objective: The study intended to analyze the therapeutic effects of inhibitors of programmed death-1 (PD-1)/ programmed cell death 1 ligand 1 (PD-L1) combined with chemotherapy for patients with advanced small cell lung cancer (SCLC), evaluate the safety of that treatment, and compare it with chemotherapy alone. Design: The research team performed a retrospective randomized controlled study. Setting: The study took place at Cangzhou Central Hospital. Participants: Participants were 72 patients with advanced SCLC who received treatment at the hospital between December 2021 and December 2022. Intervention: The research team divided participants into two groups, each with 36 participants, using the random number method: (1) the control group, which received platinum-etoposide chemotherapy, and (2) the intervention group, which received a PD-1/PD-L1 inhibitor combined with the same chemotherapy that the control group received. Outcome Measures: The research team examined: (1) short-term efficacy; (2) long-term efficacy; (3) tumor-marker levels-neuron-specific enolase (NSE), progastrin releasing peptide (ProGRP), cytokeratin-19-fragment (CYFRA21-1), and squamous cell carcinoma antigen (SCCA); (4) T lymphocyte-subset levels-cluster of differentiation 3+ (CD3+), CD4+, and CD8+; (5) adverse reactions, and (6) Karnofsky performance status (KPS) scores. Results: Compared with the control group, the intervention group's: (1) overall response rate (ORR), with P = .002, and disease control rate (DCR), with P = .041, were significantly higher; (2) median survival time was significantly longer (P = .035); (3) levels of NSE, ProGRP, CYFRA21-1, and SCCA were significantly lower (all P < .001); (4) levels of CD3+ (P = .043) and CD4+ (P < .001) levels were significantly higher; and (5) Karnofsky performance status (KPS) scores were significantly higher than those of the control group (P = .018). No difference existed in the number of adverse reactions between the groups (P > .05). Conclusions: The PD-1/PD-L1 inhibitor combined with chemotherapy can benefit advanced SCLC patients, controlling patients' conditions and improving their quality of life, with good safety.

Large-Area Flexible Memory Arrays of Oriented Molecular Ferroelectric Single Crystals with Nearly Saturated Polarization.

Molecular ferroelectrics (MFs) have been proven to demonstrate excellent properties even comparable to those of inorganic counterparts usually with heavy metals. However, the validation of their device applications is still at the infant stage. The polycrystalline feature of conventionally obtained MF films, the patterning challenges for microelectronics and the brittleness of crystalline films significantly hinder their development for organic integrated circuits, as well as emerging flexible electronics. Here, a large-area flexible memory array is demonstrated of oriented molecular ferroelectric single crystals (MFSCs) with nearly saturated polarization. Highly-uniform MFSC arrays are  prepared on large-scale substrates including Si wafers and flexible substrates using an asymmetric-wetting and microgroove-assisted coating (AWMAC) strategy. Resultant flexible memory arrays exhibit excellent nonvolatile memory properties with a low-operating voltage of <5 V, i.e., nearly saturated ferroelectric polarization (6.5 µC cm-2 ), and long bending endurance (>103 ) under various bending radii. These results may open an avenue for scalable flexible MF electronics with high performance.

Boundary-induced nucleation control: a theoretical perspective.

The pre-patterning of a substrate to create energetically more attractive or repulsive regions allows one to generate a variety of structures in physical vapor deposition experiments. A particularly interesting structure is generated if the energetically attractive region forms a rectangular grid. For specific combinations of the particle flux, the substrate temperature and the lattice size it is possible to generate exactly one cluster per cell, giving rise to nucleation control. Here, we show that the experimental observations of nucleation control can be very well understood from a theoretical perspective. For this purpose we perform, on the one hand, kinetic Monte Carlo simulations and, on the other hand, use analytical scaling arguments to rationalize the observed behavior. For several observables, characterizing nucleation control, very good agreement is found between experiment and theory. This underlines the generality of the presented mechanism to control the deposition of materials by manipulation of the direct environment.

Tunable organic hetero-patterns via molecule diffusion control.

A simple, scalable method is reported to fabricate ordered hetero-structures of organic materials using template-directed growth. The 3D extension of the structures is firstly determined by pre-pattern size and deposition amount, and can further be in situ tuned by annealing at appropriate temperature.

Area-selective growth of functional molecular architectures.

Over the last two decades, organic semiconductors have attracted increasing attention because of the applications of their inorganic counterparts in a growing number of devices. At the same time, the further success of these materials will require device processing techniques for organic semiconductors that produce high performance and high integration over large areas. Conventional top-down patterning techniques based on photolithography have served powerful methods for the surface patterning of inorganic materials. However, researchers cannot simply transfer these techniques to organic semiconductors because organic semiconductors can include small, fragile organic molecules. Alternatively, researchers have developed several nonconventional techniques, including shadow mask, printing, and vapor jet writing. However, no leading technique has emerged, and researchers are still trying to realize batch-to-batch, and even device-to-device, reproducibility. This Account summarizes recent research in our group aimed at developing methods for patterning small organic molecules that are compatible with standard device processing procedures for inorganic semiconductors. Our concept is based on classic growth dynamics by gas-phase deposition but leads to different selective growth mechanisms: "pre-patterning and patterned growth" instead of the traditional "film growth and patterning." As a result, both "foreign body" and "step edge", two possible nucleation positions for atoms and molecules during thin film growth process, can be enlarged to the mesotropic scale to define molecules within pre-determined areas. The techniques can do more than patterning. We demonstrate that these techniques can produce heteropatterning of organic structures that cannot be obtained by conventional photolithography and printing techniques. Through a combination of different growth modes, we can separate molecules at given locations on the mesotropic scale, which could lead to applications in the production of organic solar cells. Taking advantage of the differences in emission of molecules in different aggregation states, we can achieve tunable single, double- and triple-color patterns using two types of molecules. We also show that these materials can lead to devices with improved performance in features such as carrier mobility. In addition, we believe that this new photographic compatible procedure in small molecular organic semiconductors can address some issues in device performance, such as carrier transport in organic field effect transistors, by controlling domain size and numbers, and allow researchers to explore new nanoscale properties of these materials. The techniques are still in their infancy, and further research is needed to make them applicable, such as transferring the technology to cheap substrates, for example, glass and flexible plastic. For organic electronics, high-level integration, addressable, and cross-talk free device arrays are critical for producing high-performance devices at a low fabrication cost.

Pre-induced adult human peripheral blood mononuclear cells migrate widely into the degenerative retinas of rd1 mice.

BACKGROUND AIMS: Recent advances in stem cell research have raised the possibility of stem cells repairing or replacing retinal photoreceptor cells that are either dysfunctional or lost in many retinal diseases. Various types of stem cells have been used to replace retinal photoreceptor cells. Recently, peripheral blood stem cells, a small proportion of pluripotent stem cells, have been reported to mainly exist in the peripheral blood mononuclear cells (PBMCs). METHODS: In this study, the effects of pre-induced adult human PBMCs (hPBMCs) on the degenerative retinas of rd1 mice were investigated. Freshly isolated adult hPBMCs were pre-induced with the use of the conditioned medium of rat retinas for 4 days and were then labeled with chloromethyl-benzamidodialkylcarbocyanine (CM-DiI) and then transplanted into the subretinal space of the right eye of rd1 mice through a trans-scleral approach. The right eyes were collected 30 days after transplantation. The survival and migration of the transplanted cells in host retinas were investigated by whole-mount retinas, retinal frozen sections and immunofluorescent staining. RESULTS: After subretinal transplantation, pre-induced hPBMCs were able to survive and widely migrate into the retinas of rd1 mice. A few CM-DiI-labeled cells migrated into the inner nuclear layer and the retinal ganglion cell layer. Some transplanted cells in the subretinal space of rd1 host mice expressed the human photoreceptor-specific marker rhodopsin. CONCLUSIONS: This study suggests that pre-induced hPBMCs may be a potential cell source of cell replacement therapy for retinal degenerative diseases.

Different growth regimes on prepatterned surfaces: consistent evidence from simulations and experiments.

Molecule deposition on a prepatterned substrate is a recently developed technique to generate desired structures of organic molecules on surfaces via self-organization. For the case of prepatterned stripes, the time-resolved process of structure formation is studied via lattice Monte Carlo simulations. By systematic variation of the interaction strength, three distinct growth regimes can be identified: localized growth, bulge formation, and cluster formation. All three growth regimes can be recovered in the experiment when choosing appropriate organic molecules. Some key microscopic observables, reflecting the properties of the structure formation, display a non-monotonous dependence on the interaction strength.

Dewetting-Assisted Patterning of Organic Semiconductors for Micro-OLED Arrays with a Pixel Size of 1 µm.

The emergence of near-eye displays, such as head-mounted displays, is triggering a requirement for highly enhanced display resolution. High-resolution micro-displays with micro-organic light-emitting diodes (micro-OLEDs) can be a preferential candidate, owing to the mature industrialization of OLEDs along with the advantages of flexibility, light weight, and ease of processing. However, micro-OLEDs with pixel sizes down to micrometers are difficult to be achieved using conventional techniques such as fine metal mask evaporation and lithography. Here, a solution-processing approach to pattern organic semiconductors (OSCs) for micro-OLED arrays with the assistance of templated dewetting is demonstrated. Solvents containing organic functional materials are dewetted on the surface with hydrophobic/hydrophilic patterns to form ordered droplet arrays using dip-coating. Subsequently, patterned OSC films are produced by effectively controlling solvent evaporation. Micro-OLED arrays with a pixel size down to 1 µm are successfully fabricated by further deposition of emitting/electron transport layers and top electrodes. This approach can open an avenue for low-cost manufacturing of flexible and high-resolution micro-displays.

Directly Patterning Conductive Polymer Electrodes on Organic Semiconductor via In Situ Polymerization in Microchannels for High-Performance Organic Transistors.

Conductive polymers are considered promising electrode materials for organic transistors, but the reported devices with conductive polymer electrodes generally suffer from considerable contact resistance. Currently, it is still highly challenging to pattern conductive polymer electrodes on organic semiconductor surfaces with good structure and interface quality. Herein, we develop an in situ polymerization strategy to directly pattern the top-contacted polypyrrole (PPy) electrodes on hydrophobic surfaces of organic semiconductors by microchannel templates, which is also applicable on diverse hydrophobic and hydrophilic surfaces. Remarkably, a width-normalized contact resistance as low as 1.01 kΩ·cm is achieved in the PPy-contacted transistors. Both p-type and n-type organic field-effect transistors (OFETs) exhibit ideal electrical characteristics, including almost hysteresis-free, low threshold voltage, and good stability under long-term test. The facile patterning method and high device performance indicate that the in situ polymerization strategy in confined microchannels has application prospects in all-organic, transparent, and flexible electronics.

Controllable growth and field-effect property of monolayer to multilayer microstripes of an organic semiconductor.

The controllable growth of partially aligned monolayer to multilayer micrometer stripes was demonstrated by adjusting the pulling speed in a dip-coating process. The number of molecular layers decreases with the increasing pulling speed. A lower pulling speed yields mixed multilayers (3-9 monolayers). It is noteworthy that pure monolayer and bilayer microstripes over large areas can be obtained at high pulling speeds. The stripe morphology strongly depends on the pulling speed or the number of molecular layers. XRD and confocal fluorescence measurements manifest that monolayer stripes are amorphous, while multilayer stripes (> or = 2) consist of crystalline states. FET devices were fabricated on these stripes. Monolayer stripes failed to reveal a field effect due to their amorphous state. In contrast, multilayer stripes exhibit good field-effect behavior. This study provides useful information for future molecular design in controlling molecular architectures. The controllable growth from monolayer to multilayer offers a powerful experimental system for fundamental research into the real charge accumulation and transporting layers for OFETs.

Lithographical Fabrication of Organic Single-Crystal Arrays by Area-Selective Growth and Solvent Vapor Annealing.

Miniaturized organic single-crystal arrays that are addressed by reading-out circuits are crucial for high performance and high-level integration organic electronics. Here, we report a lithography compatible strategy to fabricate organic single-crystal arrays via area-selective growth and solvent vapor annealing (SVA). The organic semiconducting molecules can first selectively grow on photographically patterned drain-source electrodes, forming ordered amorphous aggregates that can further be converted to discrete single-crystal arrays by SVA. This strategy can be applied to self-align the microsized organic single crystals on predesigned locations. With this method, suppression of cross-talk among devices, organic field-effect transistors, and basic logic gate arrays with reading-out electrodes are further demonstrated.

Positioning growth of NPB crystalline nanowires on the PTCDA nanocrystal template.

Non-planar organic molecules often form amorphous films via vapor phase deposition on surfaces. In this study, we demonstrate for the first time that direct crystalline growth of non-planar NPB is possible when the orientation of initially deposited molecules on a PTCDA nanocrystal template is controlled to make it analogous to the structure of the molecular crystal. The crystalline NPB nanowires can be further positioned by controlling the site-selective growth of PTCDA nanocrystal templates at pre-determined locations. Short channel bottom contact OFET array with the NPB nanowires directly grown on electrodes were subsequently fabricated. The hole mobility of NPB nanowires is improved by 40-fold in comparison to that of the amorphous films.

Photolithography-Compatible Templated Patterning of Functional Organic Materials in Emulsion.

A solution-processed patterning of functional organic materials in emulsion is reported. The concept is to absorb microdrops onto predefined locations by hydrophilicity difference. Owing to a universal solvent used, the method can be applied to pattern variety materials on substrates of interest over large size. The figure shows Rhodamine 6G patterned film.

Addressable organic structure by anisotropic wetting.

The anisotropic wetting of functional organic molecules on a patterned surface and the development of a photolithography-compatible method to fabricate addressable organic structures is reported. For example, DtCDQA is grown on a SiO2 surface with a Au prepattern, achieving a high resolution cross-over organic structure.

High-performance and stable organic transistors and circuits with patterned polypyrrole electrodes.

High performance p-/n-type transistors and complementary inverter circuits are demonstrated using patterned polypyrrole (PPY) as pure electrodes. Strikingly, these devices show good stability under continuous operation and long-term storage conditions. Furthermore, PPY electrodes also exhibit good applicability in solution-processed and flexible devices. All these results indicate the great potential of PPY electrodes in solution-processed, all-organic, flexible, transparent, and low-power electronics.

Fabrication of split-ring resonators by tilted nanoimprint lithography.

An efficient fabrication technique for large area periodic metallic split-ring arrays has been demonstrated by the combination of tilted nanoimprint lithography and nanotransfer imprinting. The feature size of the split-rings can be adjusted by varying the key geometry parameters of the original imprinting mold. Due to the flexible nature of PDMS molds, these arrays can be patterned on curved surfaces. The molds for nanoimprint lithography and nanotransfer imprinting can be used multiple times without a loss of fidelity.