Miltefosine reinvigorates exhausted T cells by targeting their bioenergetic state.

T cell exhaustion presents a major challenge for the efficacy of both immune checkpoint inhibitors (ICBs) and chimeric antigen receptor T (CAR-T) cell immunotherapies. To address this issue, we generate hypofunctional CAR-T cells that imitate the exhaustion state. By screening a Food and Drug Administration (FDA)-approved small molecule library using this model, we identify miltefosine as a potent molecule that restores the impaired function of CAR-T cells in a PD-1/PD-L1-independent manner.

Shaping school for childhood myopia: the association between floor area ratio of school environment and myopia in China.

Aim: To investigate the association of floor area ratio (FAR), an indicator of built environments, and myopia onset.

Methods: This prospective cohort study recruited 136 753 children aged 6-10 years from 108 schools in Shenzhen, China at baseline (2016-2017). Refractive power was measured with non-cycloplegic autorefraction over a 2-year follow-up period.

E-cardiac patch to sense and repair infarcted myocardium.

Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair.

China's "coal-to-gas" policy had large impact on PM distribution during 2016-2019.

Particulate matter with an aerodynamic diameter of less than 1 μm (PM) can be extremely hazardous to human health, so it is imperative to accurately estimate the spatial and temporal distribution of PM and analyze the impact of related policies on it. In this study, a stacking generalization model was trained based on aerosol optical depth (AOD) data from satellite observations, combined with related data affecting aerosol concentration such as meteorological data and geographic data. Using this model, the PM concentration distribution in China during 2016-2019 was estimated, and verified by comparison with ground-based stations.

Unlocking CAR T cell potential: Inosine-induced stemness and enhanced potency.

Adenosine (Ado) drives immune suppression in the tumor microenvironment. In this issue of Cancer Cell, Klysz et al. investigate Ado-mediated immunosuppression.

Green Space Morphology and School Myopia in China.

Importance: China has experienced both rapid urbanization and major increases in myopia prevalence. Previous studies suggest that green space exposure reduces the risk of myopia, but the association between myopia risk and specific geometry and distribution characteristics of green space has yet to be explored. These must be understood to craft effective interventions to reduce myopia.

Robust algorithm for precise X retrieval using single observation of IPDA LIDAR.

CO column-weighted dry-air mixing ratio (X) products with high precision and spatial resolution are essential for inverting CO fluxes and promoting our understanding of global climate change. Compared with passive remote sensing methods, IPDA LIDAR, as an active remote sensing technique, offers many advantages in measuring X. However, a significant random error in IPDA LIDAR measurements causes X values calculated directly from LIDAR signals to be unqualified as the final X products.

Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models.

CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of progenitor Tex is important, but the mechanism remains unclear.

Origins of black carbon from anthropogenic emissions and open biomass burning transported to Xishuangbanna, Southwest China.

Black carbon (BC) has importance regarding aerosol composition, radiative balance, and human exposure. This study adopted a backward-trajectory approach to quantify the origins of BC from anthropogenic emissions (BC) and open biomass burning (BC) transported to Xishuangbanna in 2017. Haze months, between haze and clean months, and clean months in Xishuangbanna were defined according to daily PM concentrations of >75, 35-75, and <35 µg/m, respectively.

Constraining China's land carbon sink from emerging satellite CO observations: Progress and challenges.

Land carbon sink is a vital component for the achievement of China's ambitious carbon neutrality goal, but its magnitude is poorly known. Atmospheric observations and inverse models are valuable tools to constrain the China's land carbon sink. Space-based CO measurements from satellites form an emerging data stream for application of such atmospheric inversions.

Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells.

Chimeric antigen receptor (CAR) T cell therapy has limited efficacy against solid tumors, and one major challenge is T cell exhaustion. To address this challenge, we performed a candidate gene screen using a hypofunction CAR-T cell model and found that depletion of basic leucine zipper ATF-like transcription factor (BATF) improved the antitumor performance of CAR-T cells. In different types of CAR-T cells and mouse OT-1 cells, loss of BATF endows T cells with improved resistance to exhaustion and superior tumor eradication efficacy.

Bridging wounds: tissue adhesives' essential mechanisms, synthesis and characterization, bioinspired adhesives and future perspectives.

Bioadhesives act as a bridge in wound closure by forming an effective interface to protect against liquid and gas leakage and aid the stoppage of bleeding. To their credit, tissue adhesives have made an indelible impact on almost all wound-related surgeries. Their unique properties include minimal damage to tissues, low chance of infection, ease of use and short wound-closure time.

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies.

Until now, there has been a lack of standard and effective treatments for patients with recurrent malignant tumors or abdominal and pelvic malignancies with extensive invasion (Morris, 2000). Generally, these patients face problems such as inability to undergo surgery or chemotherapy resistance (Combs et al., 2016).

Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors.

Programmed cell death protein-1 (PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. We generated PD-1 and T cell receptor (TCR) deficient mesothelin-specific CAR-T (MPTK-CAR-T) cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study. A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion.

Clinical and laboratory characteristics of severe and non-severe patients with COVID-19: A retrospective cohort study in China.

Background: Patients diagnosed with the novel coronavirus disease (COVID-19) who develop severe symptoms need to be determined in advance so that appropriate treatment strategies are in place.

Methods: To determine the clinic features of patients diagnosed definitely with COVID-19 and evaluate risk factors for severe outcome, the medical records of hospitalized patients were reviewed retrospectively by us and data were compiled. Laboratory data from 90 cases were analyzed, and COVID-19 patients were classified into two groups (severe and non-severe) based on the severity.

In Situ Growth of Oriented Polyaniline Nanorod Arrays on the Graphite Flake for High-Performance Supercapacitors.

Polyaniline with oriented nanorod arrays could provide high surface area and relaxed nanostructure to optimize ion diffusion paths, thus enhancing the performance of the device. In this paper, we designed an all-solid symmetrical supercapacitor with good performance based on polyaniline nanorod arrays in situ-grown on a graphite flake free-standing substrate. The specific capacitance, cycle stability, and energy density of the prepared supercapacitor device were 135 F/g, 75.

Increased Expression of T-Box Transcription Factor Protein 21 (TBX21) in Skin Cutaneous Melanoma Predicts Better Prognosis: A Study Based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) Databases.

BACKGROUND T-box transcription factor protein 21 (TBX21) is expressed in immune cells and some tumor cells. Defects in TBX21 gene can cause Th1/Th2 imbalance, which is closely related to tumorigenesis. The expression and clinical value of TBX21 in skin cutaneous melanoma (SKCM) are not clear.

Engineering T Cells Using CRISPR/Cas9 for Cancer Therapy.

Recent advances in the development of gene editing technologies, especially the CRISPR/Cas 9 system, have substantially enhanced our ability to make precise and efficient changes in the genomes of various cells. In particular, the genetic engineering of T cells holds huge potential to improve the efficacy and safety of T cells-based cancer therapy. Due to its ease of use and high efficiency, CRISPR/Cas9 enables efficient gene knockout, site-specific knock-in, and genome-wide screen in T cells.

TGF-β inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors.

In recent years, chimeric antigen receptor-modified T cell (CAR T cell) therapy has proven to be a promising approach against cancer. Nonetheless, this approach still faces multiple challenges in eliminating solid tumors, one of which being the immunosuppressive tumor microenvironment (TME). Here, we demonstrated that knocking out the endogenous TGF-β receptor II (TGFBR2) in CAR T cells with CRISPR/Cas9 technology could reduce the induced Treg conversion and prevent the exhaustion of CAR T ce lls.

Improving radio-chemotherapy efficacy of prostate cancer by co-deliverying docetaxel and dbait with biodegradable nanoparticles.

Combining DNA damage repair inhibitors and chemotherapeutic agents is an emerging strategy in cancer treatment. In this study, we engineered the polycation nanoparticle (NP), which co-encapsulated DNA damage repair inhibitor Dbait and chemotherapeutic drug Docetaxel (Dtxl), using H1 nanopolymer (folate--polyethylenimine600-cyclodextrin), and the size of H1/Dbait/Dtxl was about 117 nm. We demonstrated that H1/Dbait/Dtxl enhanced the efficiency of radio-chemotherapy in prostate cancer cells by CCK-8 assay and colony-forming assay.

An Injectable Conductive Three-Dimensional Elastic Network by Tangled Surgical-Suture Spring for Heart Repair.

Designing scaffolds with persistent elasticity and conductivity to mimic microenvironments becomes a feasible way to repair cardiac tissue. Injectable biomaterials for cardiac tissue engineering have demonstrated the ability to restore cardiac function by preventing ventricular dilation, enhancing angiogenesis, and improving conduction velocity. However, limitations are still among them, such as poor mechanical stability, low conductivity, and complicated procedure.

A facile method in removal of PVP ligands from silver nanowires for high performance and reusable SERS substrate.

Silver nanowires (i.e., AgNWs) can act as effective surface-enhanced Raman spectroscopy (i.

Two-Dimensional Graphene Family Material: Assembly, Biocompatibility and Sensors Applications.

Graphene and its chemically exfoliated derivatives-GO and rGO-are the key members of graphene family materials (GFM). The atomically thick crystal structure and the large continuous π conjugate of graphene imparts it with unique electrical, mechanical, optical, thermal, and chemical properties. Although those properties of GO and rGO are compromised, they have better scalability and chemical tunability.

[Ozone Spatial-temporal Distribution and Trend over China Since 2013: Insight from Satellite and Surface Observation].

Satellite and surface observed O concentrations were applied to analyze the spatial-temporal distribution and trends of O over China. The satellite and surface observations agree well, revealing that the highest concentrations of O are distributed in East China, and with a seasonal pattern of high in summer and low in winter. Records of the diurnal variation of O over the four cities of interest (Beijing, Shanghai, Guangzhou, and Chengdu) reveal that O peaked at 15:00-16:00 each day.