Multisite Crosslinked Poly(ether-urethane)-Based Polymer Electrolytes for High-Voltage Solid-State Lithium Metal Batteries.

Utilizing solid-state polymer electrolytes (SPEs) in high-voltage Li-metal batteries is a promising strategy for achieving high energy density and safety. However, the SPEs face the challenges such as undesirable mechanical strength, low ionic conductivity and incompatible high-voltage interface. Here, a novel crosslinked poly(ether-urethane)-based SPE with a molecular cross-linked structure is fabricated to create high-throughput Li+ transport pathway. The amino-modified Zr-porphyrin-based metal-organic frameworks (ZrMOF) are introduced as multisite cross-linking nodes and polymer chain extenders. The abundant ether/ketonic-oxygen and Lewis acid sites in the SPE achieve high Li+ conductivity (5.7 × 10-4 S cm-1 at 30 °C) and Li+ transference number (0.84). The interpenetrating cross-linked structure of SPE with robust mechanical strength results in a record cycle life of 8000 h in Li||Li symmetric cell. The high structural stability of ZrMOF and abundant electron-withdrawing urethane/ureido groups in the SPE with high oxidation potential (5.1 V) enables a discharge capacity of 182 mAh g-1 at 0.3 C over 500 cycles in a LiNi0.8Co0.1Mn0.1O2||Li cell. Remarkably, a high energy density of 446 Wh kg-1 in a 1.5-Ah pouch cell is obtained with high loading cathode (≈4 mAh cm-2), demonstrating a great prospect of the current SPE for practical application in solid-state, high-voltage Li-metal batteries.

Use of muscular ultrasound to detect intensive care unit-acquired weakness: a systematic review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis aims to detecting performance of muscular ultrasound for intensive care unit (ICU)-acquired weakness (ICUAW). METHODS: We searched PubMed, Web of Science, Embase, Cochrane library, CNKI, VIP, and Wanfang databases for articles published before July 2024. A random-effects model was utilized to derive the summary estimates of sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). Additionally, the sources of heterogeneity were explored by subgroup analysis and meta-regression. RESULTS: This meta-analysis comprised ten prospective studies involving 561 participants, of whom 241 (42.96%) were diagnosed as ICUAW. Overall, muscular ultrasound exhibited good performance for detecting ICUAW, with the area of SROC curve of 0.85 (95%CI 0.82-0.88), sensitivity of 0.76 (95%CI 0.70-0.81), specificity of 0.80 (95%CI 0.74-0.84), and DOR of 12.43 (95%CI 7.98-19.38). Upon pre-defined subgroup analysis, the rectus femoris exhibited significantly superior discriminatory ability in identifying ICUAW than the non-rectus femoris, with higher SROC (0.88 [95%CI 0.85-0.91] vs. 0.76 [95%CI 0.72-0.79], p < 0.01). Moreover, cross-sectional area was more effective than thickness, with higher specificity (0.86 [95%CI 0.80-0.91] vs. 0.74 [95%CI 0.68-0.79], p = 0.02) and SROC (0.89 [95%CI 0.86-0.92] vs. 0.76 [95%CI 0.72-0.80], p < 0.01). Furthermore, integrated analysis of these two indicators revealed that the cross-sectional area of rectus femoris was statistically superior to the thickness of rectus femoris, with higher sensitivity (0.82 [95%CI 0.74-0.87] vs. 0.75 [95%CI 0.65-0.83], p < 0.05) and AUC (0.91 [95%CI 0.88-0.93] vs. 0.80 [95%CI 0.76-0.83], p < 0.01). CONCLUSIONS: Muscular ultrasound could be a reliable tool for ICUAW detection. Compared with alternative indices, the cross-sectional area of the rectus femoris exhibits superior detection efficacy and may be considered as a valuable parameter for clinical application.

Stress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway.

Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes' mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes' mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhibit cAMP/Ras/MAPK signaling or activating mitochondria respiration conferred resilience against stress-induced mitochondria damaging and epithelium hypoxia impairment, ultimately improving gut dysbiosis. These results suggest that the CRH-CRHR1-mitochondria pathway plays a pivotal role in stress-induced gut dysbiosis that could be therapeutically targeted for stress-induced gastrointestinal diseases. Yiming Zhang et.al report that psychological stress activated Corticotropin-releasing hormone (CRH)-CRH receptor type 1 (CRHR1)-mitochondria pathway to trigger gut dysbiosis and reveal CRHR1 upregulation damages mitochondria via cAMP/Ras/MAPK signaling in colonocytes.

Prognostic analysis of appendectomy versus right hemicolectomy for T1 appendiceal adenocarcinoma: a multicenter retrospective analysis.

BACKGROUND AND AIM: Appendiceal adenocarcinoma, an exceedingly rare malignancy, sparks debate on the optimal surgical approach-appendectomy or right hemicolectomy-for early-stage cases. This study aims to investigate the impact of these two surgical methods on the survival prognosis of patients with early appendiceal adenocarcinoma. METHOD: Utilizing a multicenter medical database, we gathered data from 168 patients diagnosed with T1 stage appendiceal adenocarcinoma admitted between January 2008 and January 2015. This study aims to compare the impact of different treatment modalities on the prognosis of appendiceal adenocarcinoma in these two groups. RESULT: In patients diagnosed with T1 appendiceal adenocarcinoma, the survival prognosis was not significantly improved with right hemicolectomy compared to appendectomy. Out of one hundred twenty-seven patients undergoing right colon resection, only three exhibited lymphatic metastasis, resulting in a rate of 2.3%. CONCLUSION: Simple appendectomy can fulfill the objective of achieving radical tumor resection, rendering right hemicolectomy unnecessary.

Mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease: a prospective cohort study.

OBJECTIVE: This study explored the mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD). METHODS: In this prospective community cohort study, 82 975 participants were enrolled, with the primary outcome being the incidence of new-onset ASCVD. Using the Cox proportional hazards model, the hazard ratio (HR) and 95% confidence interval (CI) for ASCVD occurrence were computed between NAFLD and non-NAFLD groups. The correlation between NAFLD and diabetes was assessed using a binary logistic regression model, and that between NAFLD, diabetes and ASCVD using a mediation model. RESULTS: During follow-up, 9471 ASCVD cases were observed. Compared with individuals without NAFLD, those with NAFLD showed an increased ASCVD risk (HR: 1.424; 95% CI: 1.363-1.488; P < 0.001). Stratifying NAFLD based on metabolic subphenotypes revealed a higher ASCVD risk in the NAFLD combined with diabetes subgroup than in the non-NAFLD subgroup (HR: 1.960; 95% CI: 1.817-2.115; P < 0.001). NAFLD was positively associated with baseline diabetes (odds ratio: 2.983; 95% CI: 2.813-3.163; P < 0.001). Furthermore, NAFLD severity was positively correlated with diabetes risk. Mediation analysis indicated that diabetes partially mediated the effect of NAFLD on ASCVD incidence, accounting for 20.33% of the total effect. CONCLUSION: NAFLD is an independent predictor of increased ASCVD risk, which may be slightly mediated by diabetes in patients with NAFLD. Evaluating NAFLD and diabetes may be crucial in the early screening and prevention of ASCVD.

[Reasons and strategies of reoperation after oblique lateral interbody fusion].

OBJECTIVE: To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion (OLIF), and put forward preventive measures. METHODS: From October 2015 to December 2019, 23 patients who underwent reoperation after OLIF in four spine surgery centers were retrospectively analyzed. There were 9 males and 14 females with an average age of (61.89±8.80) years old ranging from 44 to 81 years old. The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases, discogenic low back pain in 1 case, degenerative lumbar spondylolisthesis in 6 cases, lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases. Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation. There were 17 cases of single fusion segment, 2 of 2 fusion segments, 4 of 3 fusion segments. All the cases underwent reoperation within 3 months after the initial surgery. The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy, cage adjustment and neurolysis in 2 cases, arthroplasty and neurolysis under endoscope in 1 case, posterior laminectomy and neurolysis in 1 case, pedicle screw adjustment in 1 case, exploration and decompression under percutaneous endoscopic in 1 case, interbody fusion cage and pedicle screw revision in 1 case. Visual analogue scale (VAS) and Oswestry disability index (ODI) index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up. During the follow-up process, the phenomenon of fusion cage settlement or re-displacement, as well as the condition of intervertebral fusion, were observed. The changes in intervertebral space height before the first operation, after the first operation, before the second operation, 3 to 5 days after the second operation, 6 months after the second operation, and at the latest follow-up were measured and compared. RESULTS: There was no skin necrosis and infection. All patients were followed up from 12 to 48 months with an average of (28.1±7.3) months. Nerve root injury symptoms were relieved within 3 to 6 months. No cage transverse shifting and no dislodgement, loosening or breakage of the instrumentation was observed in any patient during the follow-up period. Though the intervertebral disc height was obviously increased at the first postoperative, there was a rapid loss in the early stage, and still partially lost after reoperation. The VAS for back pain recovered from (6.20±1.69) points preoperatively to (1.60±0.71) points postoperatively(P<0.05). The ODI recovered from (40.60±7.01)% preoperatively to (9.14±2.66)% postoperatively(P<0.05). CONCLUSION: There is a risk of reoperation due to failure after OLIF surgery. The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone, intraoperative endplate injury, significant subsidence of the fusion cage after surgery, postoperative fusion cage displacement, nerve damage, etc. As long as it is discovered in a timely manner and handled properly, further surgery after OLIF surgery can achieve better clinical results, but prevention still needs to be strengthened.

Operando chemo-mechanical evolution in LiNi0.8Co0.1Mn0.1O2 cathodes.

Ni-rich LiNi x Co y Mn z O2 (NCMxyz, x + y + z = 1, x ≥ 0.8) layered oxide materials are considered the main cathode materials for high-energy-density Li-ion batteries. However, the endless cracking of polycrystalline NCM materials caused by stress accelerates the loss of active materials and electrolyte decomposition, limiting the cycle life. Hence, understanding the chemo-mechanical evolution during (de)lithiation of NCM materials is crucial to performance improvement. In this work, an optical fiber with µÎµ resolution is designed to in operando detect the stress evolution of a polycrystalline LiNi0.8Co0.1Mn0.1O2 (P-NCM811) cathode during cycling. By integrating the sensor inside the cathode, the stress variation of P-NCM811 is completely transferred to the optical fiber. We find that the anisotropy of primary particles leads to the appearance of structural stress, inducing the formation of microcracks in polycrystalline particles, which is the main reason for capacity decay. The isotropy of primary particles reduces the structural stress of polycrystalline particles, eliminating the generation of microcracks. Accordingly, the P-NCM811 with an ordered arrangement structure delivered high electrochemical performance with capacity retention of 82% over 500 cycles. This work provides a brand-new perspective with regard to understanding the operando chemo-mechanical evolution of NCM materials during battery operation, and guides the design of electrode materials for rechargeable batteries.

[Clinicopathological characteristics of the CD8+ T lymphocytes infiltration and its mechanism in distinct molecular subtype of medulloblastoma].

OBJECTIVE: To investigate the characteristics of the CD8+ T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8+ T cells infiltration and prognosis, to study the function of C-X-C motif chemokine ligand 11 (CXCL11) and its receptor in CD8+ T cells infiltration into tumors and to explore the potential mechanism, and to provide the necessary clinicopathological basis for exploring the immunotherapy of MB. METHODS: In the study, 48 clinical MB samples (12 cases in each of 4 subtypes) were selected from the multiple medical center from 2012 to 2019. The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString PanCancer IO360TM Panel (NanoString Technologies). Immunohistochemistry (IHC) staining of formalin-fixed, paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+ T cells in the MB four subtypes. Through bioinformatics analysis, the relationship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated. The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining, and the underlying molecular mechanism of CD8+T cells infiltration into the tumor was explored. RESULTS: The characteristic index of CD8+T cells in the WNT subtype of MB was relatively high, suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes, which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus (GEO) database analysis by using R2 online data analysis platform. And the increase of CD8+T cells infiltration was positively correlated with the patient survival. The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes. Immunofluorescence staining showed the presence of CXCL11 receptor, CXCR3, on the surface of CD8+T cells, suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3. CONCLUSION: The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes. The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system, and the patients with more infiltration of CD8+T cells in tumor have better prognosis. This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB, and give a new potential therapeutic target for the future immunotherapy of MB.

The effects of two types of neighborhood factors on trajectory of internalizing and externalizing symptoms from early childhood to adolescence.

Although a robust body of previous empirical studies investigated the long-term trend of child behavior problems, limited research discussed the influences of various types of neighborhood factors on such trajectory (e.g., neighborhood structural characteristics and collective efficacy). Using a nationally representative longitudinal dataset the Fragile Families and Child Wellbeing Study (FFCWS), with six waves from 1998 to 2017, this study captures the longitudinal effects of two types of early childhood neighborhood factors on the co-development of internalizing and externalizing symptoms. Data was collected at the focal child's age 3, age 5, age 9, age 15 (N = 2,385), and the parallel-process growth curve models were applied. Results suggest that the trajectories of both internalization and externalizing symptoms showed U-shape and bidirectional relationships among internalizing and externalizing problems. The long-term effects of neighborhood social cohesion and economic disadvantages were significantly associated with children's internalizing and externalizing symptoms. The implication of this study was further discussed.

FGF signaling modulates mechanotransduction/WNT signaling in progenitors during tooth root development.

Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that Fgfr1 is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of Fgfr1 in Gli1+ progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel Piezo2 occurs after loss of FGF signaling in Gli1-CreER;Fgfr1fl/fl mice. Overexpression of Piezo2 leads to increased osteoblastic differentiation and decreased Piezo2 leads to downregulation of WNT signaling. Mechanistically, an FGF/PIEZO2/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in Fgfr1 mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration.

Visualization analysis of research frontiers and trends in the treatment of sciatic nerve injury.

Objective: To visualize and analyze the literature related to sciatic nerve injury treatment from January 2019 to December 2023, and summarize the current status, hotspots, and development trends of research in this field. Methods: Using CiteSpace and VOSviewer software, we searched the Web of Science database for literature related to the treatment of sciatic nerve injury. Then we analyzed and plotted visualization maps to show the number of publications, countries, institutions, authors, keywords, references, and journals. Results: A total of 2,653 articles were included in the English database. The annual number of publications exceeded 230, and the citation frequency increased yearly. The United States and China were identified as high-influence nations in this field. Nantong University was the leading institution in terms of close cooperation among institutions. The authors Wang Yu had the highest number of publications and were highly influential in this field. Keyword analysis and reference Burst revealed a research focus on nerve regeneration and neuropathic pain, which involve regenerative medicine and neural tissue engineering. Chronic pain resulting from sciatic nerve injury often manifests alongside anxiety, depression, cognitive-behavioral disorders, and other issues. Interventions such as stem cells, electrical stimulation, electroacupuncture, total joint replacement, pharmacological interventions, gene therapy, nerve conduits, chitosan scaffolds, and exercise promote nerve repair and alleviate pain. Schwann cells have been the focus of much attention in nerve repair and regeneration. Improving the outcome of sciatic nerve injury is a current research challenge and focus in this field. Based on keyword Burst, nerve conduits and grafts may become a potential research hotspot in the treatment of sciatic nerve injury. Conclusion: This visual analysis summarizes research trends and developments of sciatic nerve injury treatment and predicts potential research frontiers and hot directions.

Vascular architecture regulates mesenchymal stromal cell heterogeneity via P53-PDGF signaling in the mouse incisor.

Mesenchymal stem cells (MSCs) reside in niches to maintain tissue homeostasis and contribute to repair and regeneration. Although the physiological functions of blood and lymphatic vasculature are well studied, their regulation of MSCs as niche components remains largely unknown. Using adult mouse incisors as a model, we uncover the role of Trp53 in regulating vascular composition through THBS2 to maintain mesenchymal tissue homeostasis. Loss of Trp53 in GLI1+ progeny increases arteries and decreases other vessel types. Platelet-derived growth factors from arteries deposit in the MSC region and interact with PDGFRA and PDGFRB. Significantly, PDGFRA+ and PDGFRB+ cells differentially contribute to defined cell lineages in the adult mouse incisor. Collectively, our results highlight Trp53's importance in regulating the vascular niche for MSCs. They also shed light on how different arterial cells provide unique cues to regulate MSC subpopulations and maintain their heterogeneity. Furthermore, they provide mechanistic insight into MSC-vasculature crosstalk.

ARID1B maintains mesenchymal stem cell quiescence via inhibition of BCL11B-mediated non-canonical Activin signaling.

ARID1B haploinsufficiency in humans causes Coffin-Siris syndrome, associated with developmental delay, facial dysmorphism, and intellectual disability. The role of ARID1B has been widely studied in neuronal development, but whether it also regulates stem cells remains unknown. Here, we employ scRNA-seq and scATAC-seq to dissect the regulatory functions and mechanisms of ARID1B within mesenchymal stem cells (MSCs) using the mouse incisor model. We reveal that loss of Arid1b in the GLI1+ MSC lineage disturbs MSCs' quiescence and leads to their proliferation due to the ectopic activation of non-canonical Activin signaling via p-ERK. Furthermore, loss of Arid1b upregulates Bcl11b, which encodes a BAF complex subunit that modulates non-canonical Activin signaling by directly regulating the expression of activin A subunit, Inhba. Reduction of Bcl11b or non-canonical Activin signaling restores the MSC population in Arid1b mutant mice. Notably, we have identified that ARID1B suppresses Bcl11b expression via specific binding to its third intron, unveiling the direct inter-regulatory interactions among BAF subunits in MSCs. Our results demonstrate the vital role of ARID1B as an epigenetic modifier in maintaining MSC homeostasis and reveal its intricate mechanistic regulatory network in vivo, providing novel insights into the linkage between chromatin remodeling and stem cell fate determination.

Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment.

BACKGROUND: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment. METHODS: In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4-CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months. RESULTS: The percentages of patients in none CTC, OCT4-CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4-CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4-CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4-CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients. CONCLUSION: OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.

Exploring Gender Moderation: The Impact of Neighborhood Factors on Adolescent Internalizing and Externalizing Symptoms.

Limited previous studies investigated the influences of various types of neighborhood factors on adolescent behavior problems. Meanwhile, although previous theoretical frameworks suggested that gender played a significant role in terms of neighborhood impacts on adolescent behavioral problems, few studies investigated the gender differences in such neighborhood influences. Using the year 9 and year 15 data of the national dataset Future of Families and Child Wellbeing Study (FFCWS, overly sampled participants from low-income families), this study examined how the neighborhood structural and process factors can affect adolescent behavioral problems (internalizing and externalizing symptoms) and whether gender worked as a significant moderator for such relationships in the U.S. Structural equation models and multigroup SEM were estimated (N = 3411). Findings suggested that residential instability was associated with increased levels of internalizing symptoms among adolescents at age 15, whereas neighborhood social cohesion was linked to reduced levels of externalizing symptoms throughout adolescence. Furthermore, the moderating effects of gender were found for the association between residential instability and internalizing symptoms. Implications of such findings are further discussed.

A Neutrophil Hijacking Nanoplatform Reprograming NETosis for Targeted Microglia Polarizing Mediated Ischemic Stroke Treatment.

Precise and efficient regulation of microglia is vital for ischemic stroke therapy and prognosis. The infiltration of neutrophils into the brain provides opportunities for regulatory drugs across the blood-brain barrier, while hindered by neutrophil extracellular traps (NETs) and targeted delivery of intracerebral drugs to microglia. This study reports an efficient neutrophil hijacking nanoplatform (referred to as APTS) for targeted A151 (a telomerase repeat sequence) delivery to microglia without the generation of NETs. In the middle cerebral artery occlusion (MCAO) mouse model, the delivery efficiency to ischemic stroke tissues increases by fourfold. APTS dramatically reduces the formation of NETs by 2.2-fold via reprogramming NETosis to apoptosis in neutrophils via a reactive oxygen species scavenging-mediated citrullinated histone 3 inhibition pathway. Noteworthy, A151 within neutrophils is repackaged into apoptotic bodies following the death pattern reprogramming, which, when engulfed by microglia, polarizes microglia to an anti-inflammatory M2 phenotype. After four times treatment, the cerebral infarction area in the APTS group decreases by 5.1-fold. Thus, APTS provides a feasible, efficient, and practical drug delivery approach for reshaping the immune microenvironment and treating brain disorders in the central nervous system.

GENERATION OF TOLEROGENIC DENDRITIC CELLS UNDER THE PERSISTENT INFLAMMATION STIMULATION.

ABSTRACT: Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that IL-10-induced tolDCs (IL-10-tolDCs) are well-established models, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as promising therapeutic targets for ameliorating the immunosuppressed state in septic patients.

Sulfur Vacancies and 1T Phase-Rich MoS2 Nanosheets as an Artificial Solid Electrolyte Interphase for 400 Wh kg-1 Lithium Metal Batteries.

Constructing large-area artificial solid electrolyte interphase (SEI) to suppress Li dendrites growth and electrolyte consumption is essential for high-energy-density Li metal batteries (LMBs). Herein, chemically exfoliated ultrathin MoS2 nanosheets (EMoS2) as an artificial SEI are scalable transfer-printed on Li-anode (EMoS2@Li). The EMoS2 with a large amount of sulfur vacancies and 1T phase-rich acts as a lithiophilic interfacial ion-transport skin to reduce the Li nucleation overpotential and regulate Li+ flux. With favorable Young's modulus and homogeneous continuous layered structure, the proposed EMoS2@Li effectively suppresses the growth of Li dendrites and repeat breaking/reforming of the SEI. As a result, the assembled EMoS2@Li||LiFePO4 and EMoS2@Li||LiNi0.8Co0.1Mn0.1O2 batteries demonstrate high-capacity retention of 93.5% and 92% after 1000 cycles and 300 cycles, respectively, at ultrahigh cathode loading of 20 mg cm-2. Ultrasonic transmission technology confirms the admirable ability of EMoS2@Li to inhibit Li dendrites in practical pouch batteries. Remarkably, the Ah-class EMoS2@Li||LiNi0.8Co0.1Mn0.1O2 pouch battery exhibits an energy density of 403 Wh kg-1 over 100 cycles with the low negative/positive capacity ratio of 1.8 and electrolyte/capacity ratio of 2.1 g Ah-1. The strategy of constructing an artificial SEI by sulfur vacancies-rich and 1T phase-rich ultrathin MoS2 nanosheets provides new guidance to realize high-energy-density LMBs with long cycling stability.

Pleurotus ostreatus is a promising candidate of an edible 3D printing ink: Investigation of printability and characterization.

The 3D printing (3DP) technology shows great potential in the food industry, but the development of edible ink is currently insufficient. Pleurotus ostreatus (P. ostreatus) emerges as a novel promising candidate. In this study, a mixed ink was obtained by incorporating butter into P. ostreatus. The effects of different ratios of P. ostreatus and butter, as well as the influence of ink steaming were investigated on 3D printed products. The results indicated that all inks of the P. ostreatus system exhibited positive shear-thinning behavior, and the system maintained stable intermolecular hydrogen bonding when P. ostreatus powder concentration was 40 % (w/v). Furthermore, the L* value of the system was elevated for butter adding. The system with steaming exhibited superior stabilized molecular structure compared to the native system, particularly with a steaming duration of 5 min, showcasing its outstanding supporting capacity. This study suggests that P. ostreatus is a promising candidate in 3DP for the development of an edible ink that promotes innovation and nutritional food.

Neutrophil hitchhiking nanoparticles enhance bacteria-mediated cancer therapy via NETosis reprogramming.

Bacteria have shown great potential in anti-tumor treatment, and an attenuated strain of Salmonella named VNP20009 has been shown to be safe in clinical trials. However, colonized bacteria recruit neutrophils into the tumor, which release NETs to capture and eliminate bacteria, compromising bacterial-based tumor treatment. In this study, we report a neutrophil hitchhiking nanoparticles (SPPS) that block the formation of NET to enhance bacteria-mediated tumor therapy. In the 4 T1 tumor-bearing mouse model, following 24 h of bacterial therapy, there was an approximately 3.0-fold increase in the number of neutrophils in the bloodstream, while the amount of SPPS homing to tumor tissue through neutrophil hitchhiking increased approximately 2.0-fold. It is worth noting that the NETs in tumors significantly decreased by approximately 2.0-fold through an intracellular ROS scavenging-mediated NETosis reprogramming, thereby increasing bacterial vitality by 1.9-fold in tumors. More importantly, the gene drug (siBcl-2) loaded in SPPS can be re-encapsulated in apoptotic bodies by reprogramming neutrophils from NETosis to apoptosis, and enable the redelivery of drugs to tumor cells, further boosting the antitumor efficacy with a synergistic effect, resulting in about 98% tumor inhibition rate and 90% survival rate.