Multicomponent Synthesis of Imidazole-Based Ionizable Lipids for Highly Efficient and Spleen-Selective Messenger RNA Delivery.

The spleen emerges as a pivotal target for mRNA delivery, prompting a continual quest for specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate a pronounced preference for mRNA delivery into the spleen with exceptional transfection efficiency. We optimized IMIL structures by constructing and screening a multidimensional IMIL library containing multiple heads, tails, and linkers to perform a structure-activity correlation analysis. Following high-throughput in vivo screening, we identified A3B7C2 as a top-performing IMIL in spleen-specific mRNA delivery via the formulated LNPs, achieving a remarkable 98% proportion of splenic transfection. Moreover, A3B7C2-based LNPs are particularly potent in splenic dendritic cell transfection. Comparative analyses revealed that A3B7C2-based LNPs achieved a notable 2.8-fold and 12.9-fold increase in splenic mRNA transfection compared to SM102 and DLin-MC3-DMA lipid formulations, respectively. Additionally, our approach yielded an 18.3-fold enhancement in splenic mRNA expression compared to the SORT method without introducing additional anionic lipids. Collectively, these IMILs highlight promising avenues for further research in spleen-selective mRNA delivery. This work offers valuable insights for the swift discovery and rational design of ionizable lipid candidates tailored for spleen-selective transfection, thereby facilitating the application of mRNA therapeutics in spleen-related interventions.

Helper Lipid-Enhanced mRNA Delivery for Treating Metabolic Dysfunction-Associated Fatty Liver Disease.

Lipid nanoparticles (LNPs) represent the forefront of mRNA delivery platforms, yet achieving precise delivery to specific cells remains a challenge. The current targeting strategies complicate the formulation and impede the regulatory approval process. Here, through a straightforward regulation of helper lipids within LNPs, we introduce an engineered LNP designed for targeted delivery of mRNA into hepatocytes for metabolic dysfunction-associated fatty liver disease (MAFLD) treatment. The optimized LNP, supplied with POPC as the helper lipid, exhibits a 2.49-fold increase in mRNA transfection efficiency in hepatocytes compared to that of FDA-approved LNPs. CTP:phosphocholine cytidylyltransferase α mRNA is selected for delivery to hepatocytes through the optimized LNP system for self-calibration of phosphatidylcholine levels to prevent lipid droplet expansion in MAFLD. This strategy effectively regulates lipid homeostasis, while demonstrating proven biosafety. Our results present a mRNA therapy for MAFLD and open a new avenue for discovering potent lipids enabling mRNA delivery to specific cells.

Correlation between SUA and prognosis in CHF patients after revascularization.

Background: To explore the correlation between serum uric acid (SUA) and prognosis in patients with chronic heart failure (CHF) after revascularization. Methods: A total of 126 patients with CHF undergoing revascularization [coronary artery intervention (PCI) or coronary artery bypass grafting (CABG)] in the hospital were enrolled as CHF group between December 2021 and October 2022, while 126 healthy controls during the same period were enrolled as healthy control group. The levels of SUA, inflammatory factors and cardiac function in the two groups were detected. The correlation between SUA level and inflammatory factors, cardiac function levels was analyzed. All patients in CHF group were followed up for 6 months to observe prognosis. The differences in the above indexes among patients with different prognosis were compared. The risk factors of prognosis were analyzed by multivariate Logistic regression analysis, and their predictive value for prognosis was evaluated by ROC curves analysis.

Efficacy of Ganshuang granules on non-alcoholic fatty liver and underlying mechanism: a network pharmacology and experimental verification.

OBJECTIVE: To investigate the potential pharmacological mechanisms of Ganshuang granules (, GSG) in treating non-alcoholic fatty liver (NAFLD). METHODS: All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Protein-Protein interaction network, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD. Then, the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG. The levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot, respectively. RESULTS: Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD. Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD. Further experiments showed that the significantly decreased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment, as well as the expression levels of IL-6 and TNF-α in the liver. Furthermore, drug intervention increased the protein expression levels of phosphorylated-PI3K (P-PI3K) and P-AKT in the liver of the model group mice, and decreased the protein expression level of sterol regulatory element-binding protein 1. CONCLUSION: We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.

Spatio-temporal variation in soil thermal conductivity during the freeze-thaw period in the permafrost of the Qinghai-Tibet Plateau in 1980-2020.

The Qinghai-Tibet Plateau (QTP) has the largest amount of permafrost in the low and middle latitudes, making it highly susceptible to the effects of global warming. In particular, the degradation of permafrost can be intensified by anomalous amplified warming. To accurately model the hydrothermal dynamics of permafrost and its future trends, the accumulation of high-precision, long-term data for the soil thermal conductivity (STC) in the active layer is crucial. However, no previous research has systematically investigated the spatio-temporal variation in the STC on the QTP over an extended period. Therefore, this study aims to fill this gap using the XGBoost model to analyze the STC in the permafrost on the QTP from 1980 to 2020. The findings of this study provide some preliminary insights. First, areas with high variation in the STC between the freeze-thaw periods over the 40 years gradually migrated from the western region to the central region. Second, since 2015, STC in more than 90 % of the permafrost region in the thawing period has shown positive growth. While, during the freezing period, the STC also exhibited an increase over most regions of the QTP, though the western region and parts of the northeastern region exhibited a decrease. Third, the spatial center of gravity for the STC during the freezing and thawing periods from 1980 to 2020 shifted. The mean STC was larger in the eastern and northeastern regions during the freezing period and larger in the western region during the thawing period. Fourth, both alpine swamp meadow and alpine meadow exhibited a gradual increase in the STC during the freeze-thaw period from 1980 to 2020. The conclusions and data products from this study are expected to support spatiotemporal modeling of the permafrost on the QTP and assist in the prognosis for its future.

Solid-state atomic hydrogen as a broad-spectrum RONS scavenger for accelerated diabetic wound healing.

Hydrogen therapy shows great promise as a versatile treatment method for diseases associated with the overexpression of reactive oxygen and nitrogen species (RONS). However, developing an advanced hydrogen therapy platform that integrates controllable hydrogen release, efficient RONS elimination, and biodegradability remains a giant technical challenge. In this study, we demonstrate for the first time that the tungsten bronze phase H0.53WO3 (HWO) is an exceptionally ideal hydrogen carrier, with salient features including temperature-dependent highly-reductive atomic hydrogen release and broad-spectrum RONS scavenging capability distinct from that of molecular hydrogen. Moreover, its unique pH-responsive biodegradability ensures post-therapeutic clearance at pathological sites. Treatment with HWO of diabetic wounds in an animal model indicates that the solid-state atomic H promotes vascular formation by activating M2-type macrophage polarization and anti-inflammatory cytokine production, resulting in acceleration of chronic wound healing. Our findings significantly expand the basic categories of hydrogen therapeutic materials and pave the way for investigating more physical forms of hydrogen species as efficient RONS scavengers for clinical disease treatment.

Ultrahigh Enzyme Loading Metal-Organic Frameworks for Deep Tissue Pancreatic Cancer Photoimmunotherapy.

Protein drugs hold promise in treating multiple complex diseases, including cancer. The priority of protein drug application is precise delivery of substantial bioactive protein into tumor site. Metal-organic-framework (MOF) is widely considered as a promising carrier to encapsulate protein drug owing to the noncovalent interaction between carrier and protein. However, limited loading efficiency and potential toxicity of metal ion in MOF restrict its application in clinical research. Herein, a tumor targeted collagenase-encapsulating MOF via protein-metal ion-organic ligand coordination (PMOCol ) for refining deep tissue pancreatic cancer photoimmunotherapy is developed. By an expedient method in which the ratio of metal ion, histidine residues of protein and ligand is precisely controlled, PMOCol is constructed with ultrahigh encapsulation efficiency (80.3 wt%) and can release collagenase with high enzymatic activity for tumor extracellular matrix (ECM) regulation after reaching tumor microenvironment (TME). Moreover, PMOcol exhibits intensively poorer toxicity than the zeolitic imidazolate framework-8 biomineralized protein. After treatment, the pancreatic tumor with abundant ECM shows enhanced immunocyte infiltration owing to extracellular matrix degradation that improves suppressive TME. By integrating hyperthermia agent with strong near-infrared absorption (1064 nm), PMOCol can induce acute immunogenicity to host immunity activation and systemic immune memory production to prevent tumor development and recurrence.

Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis / 中华儿科杂志

Objective: To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH). Methods: This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children's hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate. Results: Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive. Conclusions: For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Anti-cancer Effect of Traditional Chinese Medicine in Regulating Cellular Senescence： A Review / 中国实验方剂学杂志

In recent years， the incidence and mortality rates of cancer have been increasing， posing a serious threat to human health. Western medicine mainly uses treatments such as surgical resection， chemotherapy， immunotherapy and targeted therapy， but they are prone to complications， drug resistance and adverse reactions. A growing number of studies have shown that traditional Chinese medicine has obvious advantages in the treatment of cancer， reducing the recurrence rate of cancer and improving the quality of survival of patients. Cellular senescence refers to a state of irreversible cell cycle growth arrest when cells cease to proliferate after a limited number of divisions， resulting in a decline in cell proliferation and differentiation capacities and physiological functions， accompanied by morphological changes such as flattening and multinuclear morphology. At the molecular level， it shows increased expression of DNA damage-related genes， reduced expression of cell cycle-related factors and significant secretory activity. The malignant development of cancer is closely related to cellular senescence. With the increasing number of cancer cell proliferation， cancer-related genes undergo continuous mutations， freeing them from cellular senescence and thus achieving unlimited proliferation. Through recent studies， it has been found that induction of tumor cell senescence， possibly through modulation of cellular DNA damage， cell cycle arrest and senescence-associated secretory phenotype （SASP）， which converts the suppressive immune tumor microenvironment to an activated immune tumor microenvironment and thus reverses the escape of tumor cell senescence， is a promising strategy for cancer therapy. However， the mechanism of cellular senescence in cancer progression is not fully understood， especially the anti-cancer role played by traditional Chinese medicine in regulating cellular senescence. This article summarized and concluded the specific molecular mechanisms of cellular senescence， the role of cellular senescence in cancer progression， and the mechanism of anti-cancer effects of traditional Chinese medicine based on cellular senescence from the perspective of regulating cellular senescence， with a view to providing ideas and methods for the anti-cancer effects of traditional Chinese medicine and the development of new drugs.

Effects of GW501516 on the injury of pulmonary artery endothelial cells induced by hypoxia and its mechanism / 中国药房

OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ （PPARδ） agonist GW501516 on the injury of pulmonary artery endothelial cells （PAECs） induced by hypoxia and its mechanism. METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs； the protein expression of PPARδ was determined by Western blot assay. The cellular model of PAECs injury was established under hypoxic conditions； using antioxidant N-acetylcysteine （NAC） as positive control， the effects of GW501516 on cell injury and reactive oxygen species （ROS） production were investigated by detecting cell apoptotic rate， cell viability， lactate dehydrogenase （LDH） activity and ROS levels. Using nuclear factor erythroid 2-related factor 2（Nrf2） activator dimethyl fumarate （DMF） as positive control， PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions； the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury （cell apoptosis， cell viability， LDH activity）， the levels of superoxide dismutase （SOD）， glutathione peroxidase （GPx）， catalase （CAT）， malondialdehyde （MDA） and ROS， the expressions of Nrf2， heme oxygenase-1 （HO-1） and cleaved-caspase-3 （C-caspase-3） protein. RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ （P＜0.05）， while GW501516 promoted the protein expression of PPARδ in hypoxia- exposed PAECs without obvious cytotoxic effects. GW501516 inhibited the apoptosis of PAECs， improved cell viability， and reduced LDH activity and ROS levels. GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD， GPx and CAT， while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway （P＜0.05）； but Nrf2 inhibitor ML385 could reverse the above effects of GW501516 （P＜0.05）. GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia （P＜0.05）. Moreover， Nrf2 inhibitor ML385 reversed the 163.com inhibition effects of GW501516 on PAECs injury （P＜0.05）. CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress， the mechanism of which may be associated with activating Nrf2.

Identification and Characterization of Peptaibols as the Causing Agents of Pseudodiploöspora longispora Infecting the Edible Mushroom Morchella.

Pseudodiploöspora longispora (previously known as Diploöspora longispora) is a pathogenic fungus of Morchella mushrooms. The molecular mechanism underlying the infection of P. longispora in fruiting bodies remains unknown. In this study, three known peptaibols, alamethicin F-50, polysporin B, and septocylindrin B (1-3), and a new analogue, longisporin A (4), were detected and identified in the culture of P. longispora and the fruiting bodies of M. sextelata infected by P. longispora. The primary amino sequence of longisporin A is defined as Ac-Aib1-Pro2-Aib3-Ala4-Aib5-Aib6-Gln7-Aib8-Val9-Aib10-Glu11-Leu12-Aib13-Pro14-Val15-Aib16-Aib17-Gln18-Gln19-Phaol20. The peptaibols 1-4 greatly suppressed the mycelial growth of M. sextelata. In addition, treatment with alamethicin F-50 produced damage on the cell wall and membrane of M. sextelata. Compounds 1-4 also exhibited inhibitory activities against human pathogens including Aspergillus fumigatus, Candida albicans, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, and plant pathogen Verticillium dahlia. Herein, peptaibols are confirmed as virulence factors involved in the invasion of P. longispora on Morchella, providing insights into the interaction between pathogenic P. longispora and mushrooms.

Corrigendum: Self-assembling and pH-Responsive protein nanoparticle as potential platform for targeted tumor therapy.

[This corrects the article DOI: 10.3389/fmolb.2023.1172100.].

Aged-Signal-Eliciting Nanoparticles Stimulated Macrophage-Mediated Programmed Removal of Inflammatory Neutrophils.

Excessive infiltration of activated neutrophils is regarded as a predominant cause of tissue injury in neutrophilic inflammation. Although programmed cell death like apoptosis maintains the homeostasis of activated neutrophils, this process is disrupted by an abnormal inflammatory response. Unlike endogenous calreticulin exposed during apoptosis, exogenous calreticulin acts as an "aged" signal and initiates premature macrophage-mediated programmed cell removal (PrCR), which is independent of apoptosis. Here, we report a nano-mediated strategy to stimulate the precise clearance of activated neutrophils initiated with artificial aged signal and alleviated inflammation. Polymeric nanoparticles PC@PLGA were fabricated by cloaking poly(lactic-co-glycolic acid) (PLGA) with a hybrid membrane derived from platelet-derived extracellular vesicles (PEVs, denoted by P) and the calreticulin-expressed membrane obtained from doxorubicin-treated cells (denoted by C). P-selectin in PEVs favors PC@PLGA to anchor activated neutrophils, while calreticulin mimics exogenous "aged" signal secreted by macrophages to trigger PrCR. We showed that PC@PLGA specifically targeted activated neutrophils and misled macrophages to recognize them as "aged" neutrophils and then initiated premature PrCR and prevented proinflammatory response and tissue damage in a mouse model of acute lung injury and severe acute pancreatitis. The collective findings indicate the efficiency of specific elimination of activated neutrophils with exogenous aged signal in improving inflammation therapy.

Self-assembling and pH-responsive protein nanoparticle as potential platform for targeted tumor therapy.

Frequent injections at high concentrations are often required for many therapeutic proteins due to their short in vivo half-life, which usually leads to unsatisfactory therapeutic outcomes, adverse side effects, high cost, and poor patient compliance. Herein we report a supramolecular strategy, self-assembling and pH regulated fusion protein to extend the in vivo half-life and tumor targeting ability of a therapeutically important protein trichosanthin (TCS). TCS was genetically fused to the N-terminus of a self-assembling protein, Sup35p prion domain (Sup35), to form a fusion protein of TCS-Sup35 that self-assembled into uniform spherical TCS-Sup35 nanoparticles (TCS-Sup35 NP) rather than classic nanofibrils. Importantly, due to the pH response ability, TCS-Sup35 NP well retained the bioactivity of TCS and possessed a 21.5-fold longer in vivo half-life than native TCS in a mouse model. As a result, in a tumor-bearing mouse model, TCS-Sup35 NP exhibited significantly improved tumor accumulation and antitumor activity without detectable systemic toxicity as compared with native TCS. These findings suggest that self-assembling and pH responding protein fusion may provide a new, simple, general, and effective solution to remarkably improve the pharmacological performance of therapeutic proteins with short circulation half-lives.

Boosting the C2H2/CO2 Separation Performance of Metal-Organic Frameworks through Fluorine Substitution.

A pair of metal-organic frameworks (MOFs) of JXNU-15 (formulated as [Co6(µ3-OH)6(BTB)2(BPY)3]n, BTB3- = benzene-1,3,5-tribenzoate and BPY = 4,4'-bipyridine) and its fluorinated JXNU-15(F) ([Co6(µ3-OH)6(SFBTB)2(BPY)3]n) based on the fluorous 1,3,5-tri(3,5-bifluoro-4-carboxyphenyl)benzene (SFBTB3-) ligands were presented. The detailed comparisons of the acetylene/carbon dioxide (C2H2/CO2) separation abilities between the isostructural JXNU-15(F) and JXNU-15 were presented. In comparison with the parent JXNU-15, the higher C2H2 uptake, larger adsorption selectivity of the C2H2/CO2 (50/50) mixture, and enhanced C2H2/CO2 separation performance endow JXNU-15(F) with highly efficient C2H2/CO2 separation performance, which is demonstrated by singe-component gas adsorptions and dynamic gas mixture breakthrough experiments. The fluorine substituents exert the crucial effects on the enhanced C2H2/CO2 separation ability of JXNU-15(F) and play the dominant role in the C2H2-framework interactions, as uncovered by computational simulations. This work illustrates a powerful fluorine substitution strategy for boosting C2H2/CO2 separation ability for MOFs.

Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms.

Interactions between gut microbiome and host immune system are fundamental to maintaining the intestinal mucosal barrier and homeostasis. At the host-gut microbiome interface, cell wall-derived molecules from gut commensal bacteria have been reported to play a pivotal role in training and remodeling host immune responses. In this article, we review gut bacterial cell wall-derived molecules with characterized chemical structures, including peptidoglycan and lipid-related molecules that impact host health and disease processes via regulating innate and adaptive immunity. Also, we aim to discuss the structures, immune responses, and underlying mechanisms of these immunogenic molecules. Based on current advances, we propose cell wall-derived components as important sources of medicinal agents for the treatment of infection and immune diseases.

Pathogen Recognition-Driven Dendritic Cell-Specific Gene Silencing and Editing.

Dendritic cells (DCs) play an essential role in both the induction of the immune response and the maintenance of immune tolerance, with any malfunction of DCs potentially causing several diseases. While gene-based therapy for DC manipulation is a promising approach, it remains challenging due to the lack of efficient delivery systems for DC targeting. Herein, we describe a novel bacterial nanomedicine (BNM) system for pathogen recognition-mediated DCs-specific gene silencing and gene editing. BNMs contain components from bacterial outer membranes and achieve efficient DC targeting through the recognition of pathogen-associated molecular patterns by pattern recognition receptors on DCs. The targeting efficiency of BNMs is reduced in DCs lacking toll-like receptor 4, which is responsible for recognizing lipopolysaccharide, a major component of the bacterial outer membrane. As a proof-of-concept demonstration, we present gene-based therapy mediated by BNMs for enhancing antigen cross-presentation in DCs, which generates a remarkable antitumor effect.

Enhanced Photocatalytic Degradation of Indoor Low Concentration Gaseous Formaldehyde by Asymmetric Silveriodate Composited with 2D or 3D Bismuth Oxybromide.

Formaldehyde is one of the most hazardous and typical indoor VOCs air pollutants. Asymmetric AgIO3 was respectively composited with 3D hierarchically structured BiOBr and 2D BiOBr nanosheets to photodegrade gas-phase formaldehyde. Ag/AgIO3 /BiOBr(CMC) demonstrated better photocatalytic performance than Ag/AgIO3 /BiOBr owning to the role of biomass solvent sodium carboxymethyl cellulose in increasing the specific surface area, reducing the band gap and changing the dominant facets. Moreover, Ag nanoparticles coming from the reduction in AgIO3 were confirmed by XRD, SEM and XPS. The surface plasma resonance effect of Ag NPs improved the efficiency of the light quantum. Besides, different exposed facets of {010} in BiOBr(CMC) and {001} in BiOBr resulted in distinct oxygen vacancy structures. O 2 2 - could be generated via a two-electron transfer pathway on the {010} dominant facets surface in AABR-CMC, leading to the change in photolysis pathway and facilitating more · OH produced by AABR-CMC. Compared with pure AgIO3 and BiOBr or BiOBr(CMC), the photocatalytic efficiency of the composites was improved significantly. Optimal photodegradation efficiency for HCHO was achieved for AABR-75 and AABR-CMC50.

Nanomedicines with high drug availability and drug sensitivity overcome hypoxia-associated drug resistance.

Tumor hypoxia heterogeneity, a hallmark of the tumor microenvironment, confers resistance to conventional chemotherapy due to insufficient drug availability and drug sensitivity in hypoxic regions. To overcome these challenges, we develope a nanomedicine, NPHPaPN, constructed with hyaluronic acid (HA) grafted with cisplatin prodrug and PEG-azobenzene for hypoxia-responsive PEG shell deshielding and loaded with a DNA damage repair inhibitor (NERi). After arriving at the tumor site, NPHPaPN deshields the PEG shell in response to hypoxia due to the enzymolysis of azobenzene and thus exposes HA. The exposed HA binds to the highly expressed CD44 on cisplatin-resistant tumor cells and mediates drug internalization, thus increasing drug availability to hypoxic tumor cells. After intracellular hyaluronidase-mediated cleavage, the HA NPs release the cisplatin prodrug and NERi, and cause enhanced DNA damage and consequent cell death, thus enhancing the drug sensitivity of hypoxic tumor cells. Eventually, NPHPaPN achieves distinct tumor growth suppression with an ∼84.4% inhibition rate.

Effects of king grass and rice straw hay on apparent digestibility and ruminal microorganisms of buffalo.

The purpose of this study was to explore the effects of Rice straw and King grass on apparent digestibility, ruminal bacterial, and fungus composition in buffaloes. Three ruminal fistulated buffaloes were used in a 3 × 2 Latin square design. The dietary treatments were king grass and straw hay. Experimental animals were kept in individual pens and concentrate was offered at 1 kg/d while roughage was fed ad libitum. Each period lasted for 15d, with the first 12d for an adaptation period, followed by a 3-day formal trial period. King grass has higher digestibility of protein. Rice straw has higher digestibility to cellulose. The results showed that when buffaloes were fed king grass and straw, Bacteroidetes were dominant in the rumen normal flora, but firmicutes were not. In addition, the results of this experiment suggest that increasing protein content in diets may be beneficial to increase the relative abundance of Proteobacteria. Similarly, higher dietary fiber content may be beneficial for increasing relative abundance of Prevotella and Staphylococcus. The dominant fungi in ruminal fluid 2 h after ingestion were aerobic fungi. These aerobic fungi most likely entered the rumen with food. Whether and how long aerobic fungi can survive in the rumen needs more research.