A Programmable Peptidic Hydrogel Adjuvant for Personalized Immunotherapy in Resected Stage Tumors.

Adjuvant treatment after surgical resection usually plays an important role in delaying disease recurrence. Immunotherapy displays encouraging results in increasing patients' chances of staying cancer-free after surgery, as reported by recent clinical trials. However, the clinical outcomes of current immunotherapy need to be improved due to the limited responses, patient heterogeneity, nontargeted distribution, and immune-related adverse effects. This work describes a programmable hydrogel adjuvant for personalized immunotherapy after surgical resection. By filling the hydrogel in the cavity, this system aims to address the limited secretion of granzyme B (GrB) during immunotherapy and improve the low immunotherapy responses typically observed, while minimizing immune-related side effects. The TLR7/8 agonist imidazoquinoline (IMDQ) is linked to the self-assembling peptide backbone through a GrB-responsive linkage. Its release could enhance the activation and function of immune cells, which will lead to increased secretion of GrB and enhance the effectiveness of immunotherapy together. The hydrogel adjuvant recruits immune cells, initiates dendritic cell maturation, and induces M1 polarized macrophages to reverse the immunosuppressive tumor microenvironment in situ. In multiple murine tumor models, the hydrogel adjuvant suppresses tumor growth, increases animal survival and long-term immunological memory, and protects mice against tumor rechallenge, leading to effective prophylactic and therapeutic responses. This work provides a potential chemical strategy to overcome the limitations associated with immunotherapy.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Loss of RSR1 function increases the abscisic acid content and improves rice quality performance at high temperature.

Rice starch regulator1 (RSR1) participates in the regulation of starch synthesis in rice, but it's function on starch synthesis and quality formation in response to high temperature is unknown. RSR1 mutation resulted in a significant increase in the abscisic acid (ABA) content in rice grains under both normal and high temperature, and the effect of high temperature on grain filling and quality formation of the rsr1 mutants was significantly reduced. The grain size, 1000-kernels weight, amylose content, gelatinization temperature, and starch viscosity of the rsr1 mutants were less sensitive to high temperature. Loss of RSR1 function increased the expression levels of starch synthesis-related genes and reduced their responses to high temperature to some extent. Besides, the percentage of germinated seeds from rsr1 mutants was significantly lower than that of the wild-type, and the difference was more significant under ABA treatment. The shoot lengths of the rsr1 mutants were remarkably shorter than those of the wild-type, which was further exacerbated by ABA treatment. These results indicated that loss function of RSR1 can improve rice quality performance at high temperature by moderately increasing the ABA content of rice grains, which provides theoretical significance for the cultivation of better-quality rice with high-temperature resistance.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop.

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation corrector Cg, and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels.

A Two-Pronged Pulmonary Gene Delivery Strategy: A Surface-Modified Fullerene Nanoparticle and a Hypotonic Vehicle.

Inhaled gene therapy poses a unique potential of curing chronic lung diseases, which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically relevant gene transfer efficacy in the lung due to the presence of numerous biological delivery barriers. Here, we introduce a simple approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo. We endowed tetra(piperazino)fullerene epoxide (TPFE)-based nanoparticles with non-adhesive surface polyethylene glycol (PEG) coatings, thereby enabling the nanoparticles to cross the airway mucus gel layer and avoid phagocytic uptake by alveolar macrophages. In parallel, we utilized a hypotonic vehicle to facilitate endocytic uptake of the PEGylated nanoparticles by lung parenchymal cells via the osmotically driven regulatory volume decrease (RVD) mechanism. We demonstrate that this two-pronged delivery strategy provides safe, wide-spread and high-level transgene expression in the lungs of both healthy mice and mice with chronic lung diseases characterized by reinforced delivery barriers.

Ultrahigh-Sensitivity Molecular Sensing with Carbon Nanotube Terahertz Metamaterials.

Terahertz (THz) electromagnetic waves strongly interact with complex molecules, making THz spectroscopy a promising tool for high-sensitivity molecular detection, especially for biomedical applications. Metamaterials are typically used for enhancing THz-molecule interactions to achieve higher sensitivities. However, a primary challenge in THz molecular sensing based on metallic metamaterials is the limited tunability of optical constants of metals. Here, we present an ultrahigh-sensitivity molecular sensor based on carbon nanotube (CNT) THz metamaterials. The sensor, consisting of a CNT cut-wire array on a Si substrate prepared by a novel two-step method, exhibits a reflectance resonance whose frequency strongly varies with the substrate composition, geometries of periodic arrays, and analyte composition. We used this sensor to detect glucose, lactose, and chlorpyrifos-methyl molecules, achieving limit-of-detection values of 30, 40, and 10 ng/mL (S/N = 3), respectively, higher than that of metallic metamaterials by 2 orders of magnitude. We attribute this ultrahigh sensitivity to the high conductivity of CNTs and the efficient adsorption of the target analyte by CNTs through van der Waals forces and π-π stacking. These easy-to-fabricate CNT-based THz metamaterials pave the way for versatile and reliable ultrahigh-sensitivity THz molecular detection.

Recent Advances in Applications of Carbon Nanotubes for Desalination: A Review.

As a sustainable, cost-effective and energy-efficient method, membranes are becoming a progressively vital technique to solve the problem of the scarcity of freshwater resources. With these critical advantages, carbon nanotubes (CNTs) have great potential for membrane desalination given their high aspect ratio, large surface area, high mechanical strength and chemical robustness. In recent years, the CNT membrane field has progressed enormously with applications in water desalination. The latest theoretical and experimental developments on the desalination of CNT membranes, including vertically aligned CNT (VACNT) membranes, composited CNT membranes, and their applications are timely and comprehensively reviewed in this manuscript. The mechanisms and effects of CNT membranes used in water desalination where they offer the advantages are also examined. Finally, a summary and outlook are further put forward on the scientific opportunities and major technological challenges in this field.

Evaluating the response of anaerobic ammonium-oxidizing bacteria to heavy metal spill in freshwater sediment.

Anaerobic ammonium-oxidizing (anammox) bacteria can play an important role in nitrogen elimination in the environment. However, the effect of heavy metals on anammox bacteria in aquatic ecosystem remains largely unknown. The present study investigated the variability of anammox bacterial community in a freshwater reservoir after a severe heavy metal spill. The richness (Chao1 richness estimator = 2-18), diversity (Shannon index = 0.26-2.04) and community structure of anammox bacteria changed considerably with sampling date, while anammox bacterial abundance (from 1.38 × 105 to 3.09 × 105 anammox bacterial 16S rRNA gene copies per gram dry sediment) was less responsive to metal spill. Anammox bacterial communities were mainly composed of Brocadia- and Anammoxoglobus-like bacteria as well as novel phylotype, however, there relative abundance varied among sampling dates. This work could add the knowledge of the response of anammox bacteria to heavy metal contamination.