An Oral PROTAC Targeting HPK1 Degradation Potentiates Anti-Solid Tumor Immunity.

Hematopoietic progenitor pinase1 (HPK1) knockout has been identified as an efficient route to enhance anti-tumor immune response. Here, this work develops an oral proteolysis targeting chimera (PROTAC) targeting HPK1 to efficiently and selectively degrade HPK1 to augment immunotherapeutic outcomes. In a postoperative tumor model of human cervical cancer in NSG mice, the orally-administrated PROTAC can reach tumors, down-regulate HPK1 levels in locally-administrated CAR-T cells, and promote their efficiency in inhibiting solid tumor recurrence, achieving 50% partial response (PR) and 50% complete response (CR).

Interpreting the additive components of multi-species distributional aggregation.

Normalized Moran's I index is an indispensable component in maintaining multi-species distributional aggregation at local scales.

Strengthened plant-microorganism interaction after topsoil removal cause more deterministic microbial assembly processes and increased soil nitrogen mineralization.

Topsoil removal, among other restoration measures, has been recognized as one of the most successful methods to restore biodiversity and ecosystem functioning in European grasslands. However, knowledge about how removal as well as other restoration methods influence interactions between plant and microbial communities is very limited. The aims of the current study were to understand the impact of topsoil removal on plant-microorganism interactions and on soil nitrogen (N) mineralization, as one example of ecosystem functioning.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth.

Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells.

Lymph nodes are crucial organs of the adaptive immune system, orchestrating T cell priming, activation and tolerance. T cell activity and function are highly regulated by lymph nodes, which have a unique structure harbouring distinct cells that work together to detect and respond to pathogen-derived antigens. Here we show that implanted patient-derived freeze-dried lymph nodes loaded with chimeric antigen receptor T cells improve delivery to solid tumours and inhibit tumour recurrence after surgery.

Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor.

The limited infiltration and persistence of chimeric antigen receptor (CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading, delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors.

Geographical patterns and determinants of insect biodiversity in China.

Insects play important roles in the maintenance of ecosystem functioning and the provision of livelihoods for millions of people. However, compared with terrestrial vertebrates and angiosperms, such as the giant panda, crested ibis, and the metasequoia, insect conservation has not attracted enough attention, and a basic understanding of the geographical biodiversity patterns for major components of insects in China is lacking. Herein, we investigated the geographical distribution of insect biodiversity across multiple dimensions (taxonomic, genetic, and phylogenetic diversity) based on the spatial distribution and molecular DNA sequencing data of insects.

Influence of Pasteurization on Maillard Reaction in Lactose-Free Milk.

In order to improve the safety and quality of lactose-free milk (LFM) Maillard reaction products (MRPs), this study used raw cow's milk as raw material and lactase hydrolysis to prepare LFM, which was heat-treated using pasteurization and then placed in storage temperatures of 4 °C, 25 °C and 37 °C to investigate the changes in the Maillard reaction (MR). The results of the orthogonal test showed that the optimal conditions for the hydrolysis of LFM are as follows: the hydrolysis temperature was 38 °C, the addition of lactase was 0.03%, and the hydrolysis time was 2.

Habitat-specific conservation priorities of multidimensional diversity patterns of amphibians in China effectively contribute to the '3030' target.

Amphibia is the most threatened animal group among all land vertebrates in the context of anthropogenic global change. Filling the conservation gaps for this taxonomic group could help achieve the ambitious target of covering 30 % of the land by 2030 ('3030' target) set by the 15-th meeting of the Conference of the Parties (COP15). In this study, we compiled the most up-to-date occurrence records and corresponding species-specific traits and phylogenies of amphibians in China (particularly those newly described in the past decade) to explore the spatial distribution patterns of multidimensional diversity (including taxonomic, functional, and phylogenetic) for different species groups (including all, endemic and threatened).

Adoptive T therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome.

Regulatory T (T) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of T cells also induce phenotype transition and functional loss, impeding clinical translation.

Urbanization increases stochasticity and reduces the ecological stability of microbial communities in amphibian hosts.

Urbanization not only profoundly alters landscape profiles, ecosystems and vertebrate faunal diversity but also disturbs microbial communities by increasing stochasticity, vulnerability, biotic homogenization, etc. However, because of the buffering effect of host species, microbial communities are expected to be influenced by both host species and urbanization stresses. Therefore, the impacts of urbanization on animals' microbial symbionts could be more complex and uncertain.

Half-millennium evidence suggests that extinction debts of global vertebrates started in the Second Industrial Revolution.

Extinction debt describes the time-lagged process of species extinction, which usually requires dozens to hundreds of years to be paid off. However, due to the lack of long-term habitat data, it is indeterminate how strong the signal of extinction debts is at the global scale and when the debts started. Here, by compiling the geographical distributions of 6120 reptiles, 6047 amphibians, and 4278 mammals and correlating them with annual forest cover data from 1500 to 1992, we show that the beginning of the Second Industrial Revolution (the mid-19 century) was the earliest signal of cumulative extinction debts for global forest-dwelling vertebrate groups.

Cell delivery devices for cancer immunotherapy.

Adoptive cell therapy (ACT) that leverages allogeneic or autologous immune cells holds vast promise in targeted cancer therapy. Despite the tremendous success of ACT in treating hematopoietic malignancies, its efficacy is limited in eradicating solid tumors via intravenous infusion of immune cells. With the extending technology of cancer immunotherapy, novel delivery strategies have been explored to improve the therapeutic potency of adoptively transferred cells for solid tumor treatment by innovating the administration route, maintaining the cell viability, and normalizing the tumor microenvironment.

Climatic Variability Caused by Topographic Barrier Prevents the Northward Spread of Invasive .

(Spreng.) R.M.

Evaluation of the Carbon Sink Capacity of the Proposed Kunlun Mountain National Park.

National parks, as an important type of nature protected areas, are the cornerstone that can effectively maintain biodiversity and mitigate global climate change. At present, China is making every effort to build a nature-protection system, with national parks as the main body, and this approach considers China's urgent goals of obtaining carbon neutrality and mitigating climate change. It is of great significance to the national carbon-neutralization strategy to accurately predict the carbon sink capacity of national park ecosystems under the background of global change.

Leveraging biomaterials for enhancing T cell immunotherapy.

The dynamic roles of T cells in the immune system to recognize and destroy the infected or mutated cells render T cell therapy a prospective treatment for a variety of diseases including cancer, autoimmune diseases, and allograft rejection. However, the clinical applications of T cell therapy remain unsatisfactory due to the tedious manufacturing process, off-target cytotoxicity, poor cell persistence, and associated adverse effects. To this end, various biomaterials have been introduced to enhance T cell therapy by facilitating proliferation, enhancing local enrichment, prolonging retention, and alleviating side effects.

Species richness and endemism pattern of Fagaceae in Southwest China and their environmental interpretation.

How to accurately model species macro-richness patterns and endemism centers is a key focus of biodiversity conservation efforts and a hot biogeographical topic. Southwest China is one of regions with high Fagaceae species richness, the species diversity patterns and driving mechanisms are unclear. In this study, the distribution pattern of species richness (SR), weighted endemism (WE), and corrected weighted endemism (CWE) indices were estimated based on 7258 occurrence points of 161 Fagaceae species in Southwest China using both occurrence-to grid method and species distribution model (SDM).

[Simulation and uncertainty analysis of natural regeneration for pine-oak forests.].

The complexity and uncertainty of forest regeneration is crucial for predicting forest ecosystem dynamics. A natural regeneration model of pine-oak forests in Qinling Mountains was constructed with competition, climate and topography factors using Bayesian statistics and global sensitivity analysis (GSA). The alternative models were based on Poisson, negative binomial (NB), zero-inflated Poisson (ZIP), and zero-inflated negative binomial (ZINB) models.

Energy-water and seasonal variations in climate underlie the spatial distribution patterns of gymnosperm species richness in China.

Studying the pattern of species richness is crucial in understanding the diversity and distribution of organisms in the earth. Climate and human influences are the major driving factors that directly influence the large-scale distributions of plant species, including gymnosperms. Understanding how gymnosperms respond to climate, topography, and human-induced changes is useful in predicting the impacts of global change.

Interfacing DNA with nanoparticles: Surface science and its applications in biosensing.

The knowledge on the mechanisms of DNA interfacing with nanoparticles holds great potential for the design, assembly and usage of DNA in biological applications. A wave of understanding and exploitation of the mechanisms in DNA-nanoparticles interfacial phenomenon has raised. Although some previous reviews have been reported, systematic and detailed reviews are rare.