Drug resistance mechanism and reversal strategy in lung cancer immunotherapy

Among all malignant tumors, lung cancer has the highest mortality and morbidity rates. The non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the most common histological subtypes. Although there are a number of internationally recognized lung cancer therapy regimens, their therapeutic effects remain inadequate. The outlook for individuals with lung carcinoma has ameliorated partly thanks to the intensive study of the tumor microenvironment and immune checkpoint inhibitors. Numerous cancers have been effectively treated with immunotherapy, which has had positive therapeutic results. Global clinical trials have validated that PD-1/PD-L1 inhibitors are effective and safe for treating lung cancer either independently or in combination, and they are gradually being recommended as systemic treatment medications by numerous guidelines. However, the immunotherapy resistance restricts the immunotherapy efficacy due to the formation of tumor immunosuppressive microenvironment and tumor mutations, and immunotherapy is only effective for a small percentage of lung cancer patients. To summarize, while tumor immunotherapy is benefiting an increasing number of lung cancer patients, most of them still develop natural or acquired resistance during immunotherapy. Consequently, a crucial and urgent topic is understanding and tackling drug resistance triggered by immunotherapy in lung cancer treatment. This review will outline the presently recognized mechanisms of immunotherapy resistance and reversal strategies in lung cancer

A Novel Estimation Method for Temperature of Magnetic Nanoparticles Dominated by Brownian Relaxation Based on Magnetic Particle Spectroscopy

This paper presents a novel method for estimating the temperature of magnetic nanoparticles (MNPs) based on AC magnetization harmonics of MNPs dominated by Brownian relaxation. The difference in the AC magnetization response and magnetization harmonic between the Fokker-Planck equation and the Langevin function was analyzed, and we studied the relationship between the magnetization harmonic and the key factors, such as Brownian relaxation time, temperature, magnetic field strength, core size and hydrodynamic size of MNPs, excitation frequency, and so on. We proposed a compensation function for AC magnetization harmonic with consideration of the key factors and the difference between the Fokker-Planck equation and the Langevin function. Then a temperature estimation model based on the compensation function and the Langevin function was established. By employing the least squares algorithm, the temperature was successfully calculated. The experimental results show that the temperature error is less than 0.035 K in the temperature range from 310 K to 320 K. The temperature estimation model is expected to improve the performance of the magnetic nanoparticle thermometer and be applied to magnetic nanoparticle-mediated hyperthermia

Superconductivity above 30 K achieved in dense scandium

Superconductivity is one of most intriguing quantum phenomena, and the quest for elemental superconductors with high critical temperature (Tc) is of great scientific significance due to their relatively simple material composition and the underlying mechanism. Here we report the experimental discovery of densely compressed scandium (Sc) becoming the first elemental superconductor with Tc breaking into 30 K range, which is comparable to the Tc values of the classic La-Ba-Cu-O or LaFeAsO superconductors. Our results show that Tconset of Sc increases from ~3 K at around 43 GPa to ~32 K at about 283 GPa (Tczero ~ 31 K), which is well above liquid neon temperature. Interestingly measured Tc shows no sign of saturation up to the maximum pressure achieved in our experiments, indicating that Tc might be even higher upon further compression.Comment: 22 pages, 16 figure

Superconductivity above 70 K observed in lutetium polyhydrides

The binary polyhydrides of heavy rare earth lutetium that shares a similar valence electron configuration to lanthanum have been experimentally discovered to be superconductive. The lutetium polyhydrides were successfully synthesized at high pressure and high temperature conditions using a diamond anvil cell in combinations with the in-situ high pressure laser heating technique. The resistance measurements as a function of temperature were performed at the same pressure of synthesis in order to study the transitions of superconductivity (SC). The superconducting transition with a maximum onset temperature (Tc) 71 K was observed at pressure of 218 GPa in the experiments. The Tc decreased to 65 K when pressure was at 181 GPa. From the evolution of SC at applied magnetic fields, the upper critical field at zero temperature {\mu}0Hc2(0) was obtained to be ~36 Tesla. The in-situ high pressure X-ray diffraction experiments imply that the high Tc SC should arise from the Lu4H23 phase with Pm-3n symmetry that forms a new type of hydrogen cage framework different from those reported for previous light rare earth polyhydride superconductors

The cascade of global trade to large climate forcing over the Tibetan Plateau glaciers.

Black carbon (BC) aerosols constitute unique and important anthropogenic climate forcers that potentially accelerate the retreat of glaciers over the Himalayas and Tibetan Plateau (HTP). Here we show that a large amount of BC emissions produced in India and China-a region of BC emissions  to which the HTP is more vulnerable compared with other regions-are related to the consumption of goods and services in the USA and Europe through international trade. These processes lead to a virtual transport pathway of BC from distant regions to the HTP glaciers. From a consumption perspective, the contribution from India to the HTP glaciers shows a rapid increasing trend while the contributions from the USA, Europe, and China decreased over the last decade. International trade aggravates the BC pollution over the HTP glaciers and may cause significant climate change there. Global efforts toward reducing the cascading of BC emissions to Asia, especially the Indian subcontinent, are urgently needed

Origin and Radiative Forcing of Black Carbon Aerosol: Production and Consumption Perspectives.

Air pollution, a threat to air quality and human health, has attracted ever-increasing attention in recent years. In addition to having local influence, air pollutants can also travel the globe via atmospheric circulation and international trade. Black carbon (BC), emitted from incomplete combustion, is a unique but representative particulate pollutant. This study tracked down the BC aerosol and its direct radiative forcing to the emission sources and final consumers using the global chemical transport model (MOZART-4), the rapid radiative transfer model for general circulation simulations (RRTM), and a multiregional input-output analysis (MRIO). BC was physically transported (i.e., atmospheric transport) from western to eastern countries in the midlatitude westerlies, but its magnitude is near an order of magnitude higher if the virtual flow embodied in international trade is considered. The transboundary effects on East and South Asia by other regions increased from about 3% (physical transport only) to 10% when considering both physical and virtual transport. The influence efficiency on East Asia was also large because of the comparatively large emission intensity and emission-intensive exports (e.g., machinery and equipment). The radiative forcing in Africa imposed by consumption from Europe, North America, and East Asia (0.01 Wm-2) was even larger than the total forcing in North America. Understanding the supply chain and incorporating both atmospheric and virtual transport may improve multilateral cooperation on air pollutant mitigation both domestically and internationally