Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Induce Fetal Wound Healing Features Revealed by Single-Cell RNA Sequencing.

The potential of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hucMSC-EVs) in wound healing is promising, yet a comprehensive understanding of how fibroblasts and keratinocytes respond to this treatment remains limited. This study utilizes single-cell RNA sequencing (scRNA-seq) to investigate the impact of hucMSC-EVs on the cutaneous wound microenvironment in mice. Through rigorous single-cell analyses, we unveil the emergence of hucMSC-EV-induced hematopoietic fibroblasts and MMP13+ fibroblasts. Notably, MMP13+ fibroblasts exhibit fetal-like expressions of MMP13, MMP9, and HAS1, accompanied by heightened migrasome activity. Activation of MMP13+ fibroblasts is orchestrated by a distinctive PIEZO1-calcium-HIF1α-VEGF-MMP13 pathway, validated through murine models and dermal fibroblast assays. Organotypic culture assays further affirm that these activated fibroblasts induce keratinocyte migration via MMP13-LRP1 interactions. This study significantly contributes to our understanding of fibroblast heterogeneities as well as intercellular interactions in wound healing and identifies hucMSC-EV-induced hematopoietic fibroblasts as potential targets for reprogramming. The therapeutic targets presented by these fibroblasts offer exciting prospects for advancing wound healing strategies.

Distribution and Main Controlling Factors of Gas and Water in Tight Sandstone Gas Fields: A Case Study of Sudong 41-33 Block in Sulige Gas Field, Ordos Basin, China.

Studying the gas-water distribution characteristics is essential in guiding the efficient development of gas fields. The relationship between gas and water in the Sudong 41-33 Block is complicated and has not been adequately researched. In recent years, gas wells have suffered from increased water/gas ratios and significant liquid loadings, which greatly affect the development of the block. A comprehensive analysis of formation water, log interpretation, and production data was conducted to determine the gas-water distribution characteristics and main controlling factors in the Sudong 41-33 Block. The findings indicate the following. (1) The formation water in the study area consists mainly of CaCl2 brine with high total dissolved solids (TDS) (with an average value of 36.06 g/L). The hydrochemical characteristics indicate that the formation water is typical sedimentary buried water under well-sealing conditions, which is markedly different from shallow river water and seawater. (2) The formation water can be categorized into three types: edge-bottom water under the gas layer (Type I), stagnant water in tight sandstone (Type II), and isolated lenticular water (Type III). The water layer distribution in the plane is mainly concentrated in the northwest region, whereas it is dispersed in other regions. On the vertical, the water layer mainly appears in P2x8-1, P2x8-2, and P1s2 Members. (3) The physical properties of the reservoir, hydrocarbon generation intensity (HGI), source rock-reservoir relationship, and mini-structure are the main factors affecting the gas-water distribution in the study area. Based on the clarification of the characteristics of gas and water distribution and its main controlling factors, it is of great importance to accurately identify the water layer, avoid the direct development of the water layer, adopt the proper production pressure differential, and carry out drainage gas production measures in time to ensure the effective development of the gas field.

Phosphocreatine promotes epigenetic reprogramming to facilitate glioblastoma growth through stabilizing BRD2.

Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and a decrease in its targets' transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.

Hypoxia-activated selectivity-improved anti-PKM2 antibody combined with prodrug TH-302 for potentiated targeting therapy in hepatocellular carcinoma.

Background: Hypoxia induces hepatocellular carcinoma (HCC) malignancies; yet it also offers treatment opportunities, exemplified by developing hypoxia-activated prodrugs (HAPs). Although HAP TH-302 combined with therapeutic antibody (Ab) has synergistic effects, the clinical benefits are limited by the on-target off-tumor toxicity of Ab. Here, we sought to develop a hypoxia-activated anti-M2 splice isoform of pyruvate kinase (PKM2) Ab combined with TH-302 for potentiated targeting therapy. Methods: Codon-optimized and hypoxia-activation strategies were used to develop H103 Ab-azo-PEG5k (HAP103) Ab. Hypoxia-activated HAP103 Ab was characterized, and hypoxia-dependent antitumor and immune activities were evaluated. Selective imaging and targeting therapy with HAP103 Ab were assessed in HCC-xenografted mouse models. Targeting selectivity, systemic toxicity, and synergistic therapeutic efficacy of HAP103 Ab with TH-302 were evaluated. Results: Human full-length H103 Ab was produced in a large-scale bioreactor. Azobenzene (azo)-linked PEG5k conjugation endowed HAP103 Ab with hypoxia-activated targeting features. Conditional HAP103 Ab effectively inhibited HCC cell growth, enhanced apoptosis, and induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) functions. Analysis of HCC-xenografted mouse models showed that HAP103 Ab selectively targeted hypoxic HCC tissues and induced potent tumor-inhibitory activity either alone or in combination with TH-302. Besides the synergistic effects, HAP103 Ab had negligible side effects when compared to parent H103 Ab. Conclusion: The hypoxia-activated anti-PKM2 Ab safely confers a strong inhibitory effect on HCC with improved selectivity. This provides a promising strategy to overcome the on-target off-tumor toxicity of Ab therapeutics; and highlights an advanced approach to precisely kill HCC in combination with HAP TH-302.

Hypoxia-activated ADCC-enhanced humanized anti-CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity.

Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on-target off-tumor toxicity limits Ab-based therapeutics. Cluster of differentiation 147 (CD147) is a tumor-associated membrane antigen overexpressed in cancer cells. Ab-based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia-activation strategies, we developed a conditional Ab-dependent cellular cytotoxicity (ADCC)-enhanced humanized anti-CD147 Ab, HcHAb18-azo-PEG5000 (HAP18). Afucosylated ADCC-enhanced HcHAb18 Ab was produced by a fed-batch cell culture system. Azobenzene (Azo)-linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia-responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement-dependent cytotoxicity, and Ab-dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor-inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia-activated ADCC-enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti-CD147 Ab drugs.

MS4A6D Promotes carrageenan-induced footpad swelling in mice through enhancing macrophages-derived inflammation.

Our previous work has demonstrated that the tetraspan MS4A6D interacts with MHC-II to be a complex that promotes macrophage activation (Mol Immunol. 2023; 160: 121-132), however, the exact role of MS4A6D in controlling macrophage-derived inflammation is still poorly understood. Here, we showed that Ms4a6d-deficient (Ms4a6d-/-) mice manifested a lower level of footpad swelling induced by subcutaneous injection of 100 µL of 1% Carrageenan (CGN, w/v) plus CaCl2 (50 mM), a phenomenon that is similar to Nlrp3-/-, Casp-1-/-, and Ilr1-/- mice. Mechanistically, F4/80+ macrophages infiltrated in the footpad tissues of the Ms4A6d-/- mice was significantly lower than that of the WT littermates, leading to dramatically lower levels of proIL-1ß in vivo. Moreover, macrophages from Ms4a6d-/- mice also showed a dramatical reduction of Il-1ß secretion following NLRP3 inflammsome activation in vitro. Interestingly, both Ms4a6dC237G mutant (Interruption of MS4A6D homodimerization) and Ms4a6dY241G mutant (deletion of heITAM motif) mice also significantly inhibited CGN-induced footpad swelling due to lower levels of Il-1ß secretion in vivo. Collectively, MS4A6D aggravates CGN-induced footpad swelling in mice by enhancing NLRP3 inflammasome in macrophages and inducing the release of IL-1ß, indicating that MS4A6D promotes the progression of acute inflammation.

Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation.

Ex vivo patient-derived tumor slices (PDTS) are currently limited by short-term viability in culture. Here, we show how bioengineered hydrogels enable the identification of key matrix parameters that significantly enhance PDTS viability compared to conventional culture systems. As demonstrated using single-cell RNA sequencing and high-dimensional flow cytometry, hydrogel-embedded PDTS tightly preserved cancer, cancer-associated fibroblast, and various immune cell populations and subpopulations in the corresponding original tumor. Cell-cell communication networks within the tumor microenvironment, including immune checkpoint ligand-receptor interactions, were also maintained. Remarkably, our results from a co-clinical trial suggest hydrogel-embedded PDTS may predict sensitivity to immune checkpoint inhibitors (ICIs) in head and neck cancer patients. Further, we show how these longer term-cultured tumor explants uniquely enable the sampling and detection of temporal evolution in molecular readouts when treated with ICIs. By preserving the compositional heterogeneity and complexity of patient tumors, hydrogel-embedded PDTS provide a valuable tool to facilitate experiments targeting the tumor microenvironment.

Characteristic alkaloids from Stemona sessilifolia with lung protective effects.

In the research on lung protective effects from the roots of Stemona sessilifolia, twenty-five Stemona alkaloids have been isolated, including four undescribed components (1, 3-5), a new natural product (2) and 20 known alkaloids (6-25). Their structures were analyzed by NMR spectra, high-resolution mass spectrum data, and other chemical methods. UPLC-QTOF/MS method was used to identify the Stemona alkaloids and summarize the fragmentation patterns of mass spectrometry. The lung-protective effects of these compounds were evaluated using MLE-12 cells induced by NNK and nm SiO2. The results showed that compounds 3, 5, 8, 10-11, 17-21 and 23 exhibited protective effects on NNK-induced cell injury. Compounds 2, 8-11, 14, 17-19 and 22 showed improvement in nm SiO2-induced lung epithelial cell injury. Compound 10 (tuberostemonine D), a representative alkaloid with a high content in Stemona sessilifolia, significantly protected C57BL/6 lung injury mice induced by nm SiO2, suggesting it a key component of Stemona alkaloids that play a protective role in lung injury. The results of in vivo activity showed that compound 10 could improve the lung injury of mice, reduce ROS content, and recover the levels of SOD and MDA in serum. Its protective effect on lung injury might be related to Nrf2 activation.

Intracellular self-aggregation of biomimetic Fe3O4 nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer.

Nanomedicines based on ferroptosis may be effective strategies for cancer therapy due to their unique inducing mechanism. However, the challenges, including non-target distribution, poor accumulation and retention of nanomedicine, have a profound impact on the effectiveness of drug delivery. Here, we developed cancer cell membrane (CCM)-coated Fe3O4 nanoparticles (NPs) modified with supramolecular precursors and loaded with sulfasalazine (SAS) for breast cancer therapy. Benefiting from the coating of the CCM, these NPs can be specifically recognized and internalized by tumor cells rapidly after being administered and form aggregates via the host-guest interaction between adamantane (ADA) and cyclodextrins (CD), which in turn effectively reduces the exocytosis of tumor cells and prolongs the retention time. In vitro and in vivo studies showed that Fe3O4 NPs possessed effective cellular uptake and precise specific accumulation in tumor cells and tissues through CCM-targeted supramolecular in situ aggregation, demonstrating enhanced ferroptosis-inducing therapy of breast cancer. Overall, this work provided a supramolecular biomimetic platform to achieve targeted delivery of Fe3O4 NPs with high efficiency and precise self-assembly for improved cancer therapy.

Impact of Preoperative Sleep Disturbances on Postoperative Delirium in Patients with Intracranial Tumors: A Prospective, Observational, Cohort Study.

Background: Postoperative delirium (POD) is prevalent in craniotomy patients and is associated with high mortality. Sleep disturbances are receiving increasing attention from clinicians as associated risk factors for postoperative complications. This study aimed to determine the impact of preoperative sleep disturbances on POD in craniotomy patients. Methods: We recruited 130 patients undergoing elective craniotomy for intracranial tumors between May 1st and December 30th, 2022. Preoperative subjective sleep disturbances were assessed using the Pittsburgh Sleep Quality Index on the day of admission. We also measured objective perioperative sleep patterns using a dedicated sleep monitoring device 3 days before and 3 days after the surgery. POD was assessed twice daily using the Confusion Assessment Model for the Intensive Care Unit within the first week after craniotomy. Results: Preoperative sleep disturbances were diagnosed in 49% of the study patients, and POD was diagnosed in 22% of all the study patients. Sleep disturbances were an independent risk factor for POD (OR: 2.709, 95% CI: 1.020-7.192, P = 0.045). Other risk factors for POD were age (OR: 3.038, 95% CI: 1.195-7.719, P = 0.020) and the duration of urinary catheterization (OR: 1.246, 95% CI: 1.025-1.513, P = 0.027). Perioperative sleep patterns (including sleep latency, deep sleep duration, frequency of awakenings, apnea-hypopnea index, and sleep efficiency) were significantly associated with POD. Conclusion: This study demonstrated that preoperative sleep disturbances predispose patients undergoing craniotomy to POD, also inferred a correlation between perioperative sleep patterns and POD. The targeted screening and intervention specifically for sleep disturbances during the perioperative period are immensely required.

High-voltage lithium-metal batteries enabled by ethylene glycol bis(propionitrile) ether-LiNO3 synergetic additives.

The employment of Li metal anodes is a key to realizing ultra-high energy batteries. However, the commercialization of lithium metal batteries (LMBs) remains challenging partially due to the thermodynamic instability and competitive oxidative decomposition of the solvent. Herein, a bi-functional electrolyte for stabilizing the interfaces of both the Li metal anode and LiCoO2 (LCO) cathode is designed by introducing lithium nitrate (LiNO3) through Ethylene Glycol Bis(Propionitrile) Ether (DENE). For the anode, the C8H12N2O2-LiNO3 coordination-solvation contributes to forming a stable Li3N-enhanced solid electrolyte interphase (SEI), which increases the average Li coulombic efficiency (CE) up to 98.5%. More importantly, in situ electrochemical dilatometry further reveals that the highly reversible behavior and a low volume expansion of lithium deposition are related to the stable Li3N-enhanced SEI. The designed electrolyte enables the Li‖LCO cell to achieve an average CE of 99.2% and a high capacity retention of 88.2% up to 4.6 V after 100 cycles. This work provides a strategic guidance in developing high-voltage Li‖LCO batteries with dual electrolyte additives.

Associations between perioperative sleep patterns and clinical outcomes in patients with intracranial tumors: a correlation study.

Objective: Although the quality of perioperative sleep is gaining increasing attention in clinical recovery, its impact role remains unknown and may deserve further exploration. This study aimed to investigate the associations between perioperative sleep patterns and clinical outcomes among patients with intracranial tumors. Methods: A correlation study was conducted in patients with intracranial tumors. Perioperative sleep patterns were assessed using a dedicated sleep monitor for 6 consecutive days. Clinical outcomes were gained through medical records and follow-up. Spearman's correlation coefficient and multiple linear regression analysis were applied to evaluate the associations between perioperative sleep patterns and clinical outcomes. Results: Of 110 patients, 48 (43.6%) were men, with a median age of 57 years. A total of 618 days of data on perioperative sleep patterns were collected and analyzed. Multiple linear regression models revealed that the preoperative blood glucose was positively related to the preoperative frequency of awakenings (ß = 0.125; 95% CI = 0.029-0.221; P = 0.011). The level of post-operative nausea and vomiting was negatively related to perioperative deep sleep time (ß = -0.015; 95% CI = -0.027--0.003; P = 0.015). The level of anxiety and depression was negatively related to perioperative deep sleep time, respectively (ß = -0.048; 95% CI = -0.089-0.008; P = 0.020, ß = -0.041; 95% CI = -0.076-0.006; P = 0.021). The comprehensive complication index was positively related to the perioperative frequency of awakenings (ß = 3.075; 95% CI = 1.080-5.070; P = 0.003). The post-operative length of stay was negatively related to perioperative deep sleep time (ß = -0.067; 95% CI = -0.113-0.021; P = 0.005). The Pittsburgh Sleep Quality Index was positively related to perioperative sleep onset latency (ß = 0.097; 95% CI = 0.044-0.150; P < 0.001) and negatively related to perioperative deep sleep time (ß = -0.079; 95% CI = -0.122-0.035; P < 0.001). Conclusion: Perioperative sleep patterns are associated with different clinical outcomes. Poor perioperative sleep quality, especially reduced deep sleep time, has a negative impact on clinical outcomes. Clinicians should, therefore, pay more attention to sleep quality and improve it during the perioperative period. Clinical trial registration: http://www.chictr.org.cn, identifier: ChiCTR2200059425.

Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy.

The mucosal barrier remains a major barrier in the pulmonary drug delivery system, as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles (NPs). Herein, we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin (marked as QR-SF (PF127) NPs), aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR. The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins, thus facilitating the diffusion of SF(PF127) NPs in the mucus layer. The QR-SF (PF127) NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties. Fluorescence recovery after photobleaching (FRAP) assay and transepithelial transport test showed that QR-SF (PF127) NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model. Notably, a large amount of QR-SF (PF127) NPs distributed uniformly in the mice airway section, indicating the good retention of NPs in the respiratory tract. The mice melanoma lung metastasis model was established, and the therapeutic effect of QR-SF (PF127) NPs was significantly improved in vivo. PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhance mucus penetration efficiency in the pulmonary drug delivery system.

Nucleus-selective self-augmenting cascade nanoassemblies for targeted synergistic photo-chemo therapy of tumors.

A nucleus-targeted enzyme prodrug nanocomposite, assembled from ß-cyclodextrin-lysine (CL), catalase (CAT), Pt(IV) and chlorin e6 (Ce6), was developed for self-augmenting cascade photo-chemo therapy of tumors. It can effectively transport through the cytoplasm and accumulate in the nucleus, thereby significantly inhibiting tumor growth and lung metastasis.

Tetraspan MS4A6D is a coreceptor of MHC class II antigen (MHC-II) that promotes macrophages-derived inflammation.

Our previous research demonstrated that the tetraspan MS4A6D is an adapter of VSIG4 that controls NLRP3 inflammasome activation (Sci Adv. 2019: eaau7426); however, the expression, distribution and biofunction of MS4A6D are still poorly understood. Here, we showed that MS4A6D is restricted to mononuclear phagocytes and that its gene transcript is controlled by the transcription factor NK2 homeobox-1 (NKX2-1). Ms4a6d-deficient (Ms4a6d-/-) mice showed normal macrophage development but manifested a greater survival advantage against endotoxin (lipopolysaccharide) challenge. Mechanistically, MS4A6D homodimers crosslinked with MHC class II antigen (MHC-II) to form a surface signaling complex under acute inflammatory conditions. MHC-II occupancy triggered Tyr241 phosphorylation in MS4A6D, leading to activation of SYK-CREB signaling cascades, further resulting in augmenting the transcription of proinflammatory genes (Il1b, Il6 and Tnfa) and amplifying the secretion of mitochondrial reactive oxygen species (mtROS). Deletion of Tyr241 or interruption of Cys237-mediated MS4A6D homodimerization in macrophages alleviated inflammation. Importantly, both Ms4a6dC237G and Ms4a6dY241G mutation mice phenocopied Ms4a6d-/- animals to prevent endotoxin lethality, highlighting MS4A6D as a novel target for treating macrophage-associated disorders.

Bioactive fatty acid analog-derived hybrid nanoparticles confer antibody-independent chemo-immunotherapy against carcinoma.

Typical chemo-immunotherapy against malignant carcinoma, is characterized by the combined application of chemotherapeutic agents and monoclonal antibodies for immune checkpoint blockade (ICB). Temporary ICB with antibodies would not depress tumor intrinsic PD-L1 expression and potential PD-L1 adaptive upregulation during chemotherapy, thus exerting limited immunotherapy efficacy. Herein, we developed novel polymer-lipid hybrid nanoparticles (2-BP/CPT-PLNs) for inducing PD-L1 degradation by inhibiting palmitoylation with bioactive palmitic acid analog 2-bromopalmitate (2-BP) to replace PD-L1 antibody (αPD-L1) for ICB therapy, thus achieving highly efficient antitumor immune via immunogenic cell death (ICD) induced by potentiated chemotherapy. GSH-responsive and biodegradable polymer-prodrug CPT-ss-PAEEP10 assisted as a cationic helper polymer could help to stabilize 2-BP/CPT-PLNs co-assembled with 2-BP, and facilitate the tumor site-specific delivery and intracellular release of water-insoluble camptothecin (CPT) in vivo. 2-BP/CPT-PLNs would reinforce cytotoxic CD8+ T cell-mediated antitumor immune response via promoting intratumoral lymphocytes cells infiltration and activation. 2-BP/CPT-PLNs significantly prevented melanoma progression and prolonged life survival of mice beyond the conventional combination of irinotecan hydrochloride (CPT-11) and αPD-L1. Our work first provided valuable instructions for developing bioactive lipid analogs-derived nanoparticles via lipid metabolism intervention for oncotherapy.

Efficacy of short-chain polypeptide-based EEN formulas in alleviating intestinal injury in children with Crohn's disease: a single-center study in China.

Short-chain polypeptides are composed of three to nine amino acids, which can be absorbed by the intestinal tract without digestive enzymes and ATP energy. Crohn's disease (CD) is a chronic non-specific disease derived from inflammation and damage of the gastrointestinal tract. In this study, we aim to investigate the effect of short-chain polypeptide-based exclusive enteral nutrition (EEN) formulas on intestinal injury in Chinese children with active CD. From January 2013 to January 2019, a total of 84 consecutive children with a diagnosis of Crohn's disease (CD) in the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University, were divided into mild and moderate-to-severe active CD groups. Each group was further divided into two subgroups: drug group and short-chain polypeptide plus drug group. Tests were carried out on the levels of intestinal fatty acid binding protein (I-FABP) in the blood, fecal calprotectin (FC), and occludin protein in the intestinal mucosa 1 day before treatment and 8 weeks after treatment. Endoscopic and histopathological observations were detected to compare the changes in intestinal injury in children with active CD. After 8 weeks of treatment, the SES-CD scores and Chiu scores of the ileocecal area and terminal ileum of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD in short-chain polypeptide plus drug group were significantly lower than those in the drug group. The OD value of occludin in the terminal ileum and ileocecal area of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD after short-chain polypeptide-based EEN formulas and drug treatment was significantly higher than those in the drug group (p < 0.05). Meanwhile, the levels of FC and I-FABP were significantly decreased (p < 0.05). The results showed that short-chain polypeptide-based EEN formulas effectively alleviate intestinal injury in children with active CD.

Ultrasmall graphene oxide for combination of enhanced chemotherapy and photothermal therapy of breast cancer.

Combination of chemotherapy and photothermal therapy (PTT) is an effective way for the treatment of cancer. Graphene oxide (GO) with a large specific surface area and strong near-infrared (NIR) absorbance have been widely used as both the chemotherapeutic carriers and photothermal agents. The smaller lateral size and higher oxidation degree of GO corresponding to better dispersion in water and lower cytotoxicity. Therefore, the preparation of ultrafine GO nanosheets (UGO) with the controlled size and high oxidation degree is of significant importance to meet the demands of biological applications. Herein, we developed a versatile drug delivery nanoplatform based on poly(dopamine) (PDA) modified ultrasmall graphene oxide (UGO) with small size (average size of 30 nm) and high oxidation content (45 wt. %). The fabricated PDA-modified UGO (UGP) exhibits well biocompatibility, excellent photothermal performance and high drug loading capacity of doxorubicin (DOX). Under NIR laser irradiation, the photothermal-induced release of DOX could achieve the combination of chemotherapy and PTT for efficient therapy of breast cancer. This work established UGO as a novel drug delivery with excellent photothermal performance for the combination of chemotherapy and PTT of tumors.

Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO2/ICG@ZIF-8, which was capable of self-sufficient O2 delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO2 and indocyanine green (ICG) form CaO2/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO2 reacts with water under acidic conditions to produce O2 so CaO2/ICG@ZIF-8 has an excellent O2 supply capacity, which is essential for PDT. Moreover, CaO2/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO2/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO2/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO2/ICG@ZIF-8 degradation are essential elements for the body, so CaO2/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.