Single-cell analysis reveals the disparities in immune profiles between younger and elder patients.

PURPOSE: The immune profiles of elder patients with non-small cell lung cancer (NSCLC) differ significantly from those of younger patients. The tumor microenvironment (TME) is a crucial factor in cancer progression and therapeutic responses. The present study aims to decipher the difference in TME between younger and elderly patients with lung cancers. METHODS: We downloaded single-cell RNA data from public databases. The algorithm of uniform manifold approximation and projection (UMAP) was applied to cluster and visualize single-cell sequencing data. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) analysis were performed to evaluate the physiological functional characteristics in sub-group cells. CellPhoneDB was used to identify cell-cell interactions between immune cells within TME. RESULTS: We conducted single-cell RNA sequencing on 96,491 cells from elderly patients and 169,207 cells from younger patients, respectively. We observed that epithelial cells were the predominant component of the TME in younger patients, whereas T/NK cells were the predominant cell type in the TME of elderly patients. We also found that there was a higher proportion of Tregs and a lower proportion of NK, effector CD8+T and γδT cells in elder patients compared with younger patients. In addition, a comparative GSEA analysis of NK cells between older and younger patients revealed that the pathways of Parkinson's disease, Alzheimer's disease, mismatch repair, and base excision repair were up-regulated in NK cells from elderly patients, while the pathways related to natural killer cell-mediated cytotoxicity and allograft rejection were downregulated. Furthermore, we identified tumor-associated neutrophils (TANs) in elder patients, and GSVA analysis demonstrated that the pathway of angiogenesis was upregulated, and the pathway of interferon_γ_response, inflammatory_response, TNFα_signaling_via_NFκB pathways were downregulated. Importantly, the pro-inflammatory response scores of complement C1q C chain positive (C1QC+) macrophages, tissue-resident macrophages (TRM), non-classical monocytes (NCM), secreted phosphoprotein 1 positive (SPP1+) macrophages, and classical monocytes (CM) in elder patients were significantly lower compared to those in younger patients. Finally, cell-to-cell communication analyses unveiled the disparities in regulatory patterns between elder and younger patients, namely the pairs of CXCL13-ACKR4 and CSF1-SIRPA in elder patients and the pairs of CTLA4-CD86 and TIGIT-NECTIN2 in younger patients. CONCLUSION: This study reveals the distinct immune profiles between younger and elder NSCLC patients, and the elder patients were likely to exhibit a more immunosuppressive TME and attenuated tumor-killing capability compared with younger patients.

Value of ultrathin bronchoscope in improving the endobronchial ultrasound localization rate and diagnosing peripheral pulmonary nodules by cryobiopsy.

BACKGROUND: A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS. METHODS: We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups. RESULTS: Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P < 0.001). The diagnostic yield of cryobiopsy specimens from the UTB group was significantly higher compared to the thin bronchoscope group (54.0% vs. 30.1%, respectively; p = 0.006). Univariate analysis demonstrated that the cryobiopsy diagnostic yields of the UTB group were significantly higher for lesions ≤ 20 mm, benign lesions, upper lobe lesions, lesions located lateral one-third from the hilum, and lesions without bronchus sign. CONCLUSIONS: Ultrathin bronchoscopy combined with cryobiopsy has a superior ultrasound localization rate and diagnostic yield compared to a combination of cryobiopsy and thin bronchoscopy.

Nursing students' perceptions of a good death: A mixed method study.

BACKGROUND: Social aging tendencies and increasing chronic disease burdens draw people's attention to the concept of a good death. OBJECTIVE: This study investigated how Chinese nursing students perceive a good death. DESIGN: A mixed quantitative and qualitative design. PARTICIPANTS AND SETTING: Four hundred and ninety-three nursing students from one mainland China university and one Macao SAR university participated in the study. METHODS: The Good Death Inventory (Chinese version) was used to collect quantitative data. Qualitative data was collected through semi-structured interviews. Four hundred seventy-two questionnaires were collected, and 21 participants were interviewed. Quantitative and qualitative data were analyzed through statistics and thematic analysis, respectively. RESULTS: Chinese nursing students gained an average score of 3.76 ± 0.39 in GDI-C. Students from mainland China, female, and with senior grades scored higher in the GDI-C (p < 0.05). Students' good death perception comprised four themes: positive psychological status, no physical suffering, open and supportive social surroundings, and spiritual/religious perfection. Mainland China and Macao students showed high consistency in their ranking of good death dimensions. The first five rankings in GDI-C were domains of being respected as an individual, dying in a favorite place, preparation for death, good relationships with family/medical staff, and environmental comfort. The last five rankings in GDI-C were domains of religious and spiritual comfort, independence, unawareness of death, pride and beauty, and not being a burden to others. CONCLUSION: Chinese nursing students had a moderate degree of good death perception, characterized by the emphasis on social domains. Nursing students from mainland China and Macao SAR shared a similar perception of a good death in the Chinese context. More hospice care opportunities should be provided to students to train their empathy. Educators should guide students to apply principles of respect/dignity and open communication in the nursing practice.

Light-Powered Directional Ion Transport via PFN-Br/MoS2 Heterogeneous Membranes: Band Alignment and Activation Energy Barrier Engineering.

Biological photoresponsive ion transport systems consistently attract researchers' attention owing to their remarkable functions of harvesting energy from nature and participating in visual perception systems. Designing and constructing artificial light-driven ion transport devices to mimic biological counterparts remains a challenge owing to fabrication limitations in nanoconfined spaces. Herein, a typical conjugated polyelectrolyte (PFN-Br) was assembled onto a laminated MoS2M using simple solution-processing vacuum filtration, resulting in a heterogeneous three- and two-dimensional nanoporous membrane. The designed band alignment between PFN-Br and MoS2 enables effective directional ion transport under irradiation in an equilibrium solution, even against a 30-fold concentration gradient. The staggered energy structure of PFN-Br and MoS2 enhances charge separation and establishes a photogenerated potential as the driving force for ion transport. Additionally, the activation energy barrier for ion transport across the heterogeneous membrane decreased by 60% after light irradiation, considerably improving ion transport flux. The easy fabrication and high performance of the membrane in light-powered ion transport provide promising approaches for designing nanofluidic devices with possible applications in energy conversion, light-enhanced biosensing, and photoresponsive ionic devices.

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.

Impact of Shenmai Injection Combined with Chemotherapy on T-cell Subsets and Cytokine Profiles in Patients with Advanced Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) represents a significant portion of lung cancer cases, with a poor prognosis and limited treatment options for advanced stages. Enhancing the effectiveness of chemotherapy through adjunctive therapies is a critical area of research. Objective: To evaluate the effect of Shenmai injection combined with chemotherapy on T-cell subsets and cytokine expression in patients with advanced NSCLC. Methods: A comparative prospective study was conducted, and a total of 96 patients with advanced NSCLC were selected. Patients were divided into two groups based on different chemotherapy regimens: an observation group (48 patients) receiving Shenmai injection combined with chemotherapy and a control group (48 patients) receiving chemotherapy alone. The study measures and compares the levels of T-cell subsets (CD3+, CD4+, CD4+/CD8+) and cytokines (IL-2, IL-4, IL-5, IL-6, TNF-α, IFN-γ, VEGF, bFGF, CA125, and CEA) before and after treatment in both groups. Statistical analysis was performed on the collected data. Results: Significant changes were observed in the levels of T-cell subsets and cytokines before and after chemotherapy in both groups (P < .05). Compared with the control group, the observation group exhibited significant improvement in T-cell subsets CD3+, CD4+, and CD4+/CD8+ (P < .05). Furthermore, the levels of cytokines IL-2, IL-4, IL-5, IL-6, TNF-α, IFN-γ, VEGF, bFGF, CA125, and CEA were significantly lower in the observation group compared to the control group (all P < .05). Conclusions: Shenmai injection combined with chemotherapy enhances the cellular immune function in patients with advanced NSCLC. This combination therapy not only reverses tumor progression but also improves the overall therapeutic effect, suggesting a promising adjunctive treatment strategy for advanced NSCLC.

Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

Crucial Role of Metal Coordination Number in Optimizing Electrocatalyst Activity of Holey Large-Area 2D Ru Nanosheets.

Low-dimensional metal nanostructures have attracted considerable research attention, owing to their potential as catalysts. A controlled reductive phase transition of monolayer RuO2 nanosheets could provide an effective way to produce holey large-area 2D Ru nanosheets with tailored defect structures and metal coordination number. The locally optimized holey Ru metal nanosheet, with a metal coordination number of ∼10.2, exhibited excellent electrocatalytic activity for the hydrogen evolution reaction (HER) with a reduced overpotential of 38 mV in a 1 M KOH electrolyte. The creation of a highly anisotropic holey nanosheet morphology with optimization of local structure was quite effective in developing efficient catalyst materials. The universal importance of controlling the coordination number was confirmed through a comparative study of Ru nanoparticles, which showed optimized HER activity with an identical metal coordination number. The coordination number plays a pivotal role in governing electrocatalytic activity, which could be ascribed to the formation of the most active structure for HER at most 2 defects near active sites (2,2'), resulting in the stabilization of a dihydrogen Ru-(H2) intermediate and the increased contribution of Volmer-Tafel mechanism.

Ammonolysis-Driven Exsolution of Ru Nanoparticle Embedded in Conductive Metal Nitride Matrix to Boost Electrocatalyst Activity.

Exsolution is an effective method for synthesizing robust nanostructured metal-based functional materials. However, no studies have investigated the exsolution of metal nanoparticles into metal nitride substrates. In this study, a versatile nitridation-driven exsolution method is developed for embedding catalytically active metal nanoparticles in conductive metal nitride substrates via the ammonolysis of multimetallic oxides. Using this approach, Ti1-xRuxO2 nanowires are phase-transformed into holey TiN nanotubes embedded with exsolved Ru nanoparticles. These Ru-exsolved holey TiN nanotubes exhibit outstanding electrocatalytic activity for the hydrogen evolution reaction with excellent durability, which is significantly higher than that of Ru-deposited TiN nanotubes. The enhanced stability of the Ru-exsolved TiN nanotubes can be attributed to the Ru nanoparticles embedded in the robust metal nitride matrix and the formation of interfacial Ti3+─N─Ru4+ bonds. Density functional theory calculations reveal that the exsolved Ru nanoparticles have a lower d-band center position and optimized hydrogen affinity than deposited Ru nanoparticles, indicating the superior electrocatalyst performance of the former. In situ Raman spectroscopic analysis reveals that the electron transfer from TiN to Ru nanoparticles is enhanced during the electrocatalytic process. The proposed approach opens a new avenue for stabilizing diverse metal nanostructures in many conductive matrices like metal phosphides and chalcogenides.

Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway.

BACKGROUND: Targeting ferroptosis mediated by autophagy presents a novel therapeutic approach to breast cancer, a mortal neoplasm on the global scale. Pyruvate dehydrogenase kinase isozyme 4 (PDK4) has been denoted as a determinant of breast cancer metabolism. The target of this study was to untangle the functional mechanism of PDK4 in ferroptosis dependent on autophagy in breast cancer. METHODS: RT-qPCR and western blotting examined PDK4 mRNA and protein levels in breast cancer cells. Immunofluorescence staining appraised light chain 3 (LC3) expression. Fe (2 +) assay estimated total iron level. Relevant assay kits and C11-BODIPY (591/581) staining evaluated lipid peroxidation level. DCFH-DA staining assayed intracellular reactive oxygen species (ROS) content. Western blotting analyzed the protein levels of autophagy, ferroptosis and apoptosis-signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) pathway-associated proteins. RESULTS: PDK4 was highly expressed in breast cancer cells. Knockdown of PDK4 induced the autophagy of breast cancer cells and 3-methyladenine (3-MA), an autophagy inhibitor, countervailed the promoting role of PDK4 interference in ferroptosis in breast cancer cells. Furthermore, PDK4 knockdown activated ASK1/JNK pathway and ASK1 inhibitor (GS-4997) partially abrogated the impacts of PDK4 absence on the autophagy and ferroptosis in breast cancer cells. CONCLUSION: To sum up, deficiency of PDK4 activated ASK1/JNK pathway to stimulate autophagy-dependent ferroptosis in breast cancer.

Photo-Driven Ion Directional Transport across Artificial Ion Channels: Band Engineering of WS2 via Peptide Modification.

Biological photo-responsive ion channels play important roles in the important metabolic processes of living beings. To mimic the unique functions of biological prototypes, the transition metal dichalcogenides, owing to their excellent mechanical, electrical, and optical properties, are already used for artificial intelligent channel constructions. However, there remain challenges to building artificial bio-semiconductor nanochannels with finely tuned band gaps for accurately simulating or regulating ion transport. Here, two well-designed peptides are employed for the WS2 nanosheets functionalization with the sequences of PFPFPFPFC and DFDFDFDFC (PFC and DFC; P: proline, D: aspartate, and F: phenylalanine) through cysteine (Cys, C) linker, and an asymmetric peptide-WS2 membrane (AP-WS2M) could be obtained via self-assembly of peptide-WS2 nanosheets. The AP-WS2M could realize the photo-driven anti-gradient ion transport and vis-light enhanced osmotic energy conversion by well-designed working patterns. The photo-driven ion transport mechanism stems from a built-in photovoltaic motive force with the help of formed type II band alignment between the PFC-WS2 and DFC-WS2. As a result, the ions would be driven across the channels of the membrane for different applications. The proposed system provides an effective solution for building photo-driven biomimetic 2D bio-semiconductor ion channels, which could be extensively applied in the fields of drug delivery, desalination, and energy conversion.

N-Acetyltransferase 10 represses Uqcr11 and Uqcrb independently of ac4C modification to promote heart regeneration.

Translational control is crucial for protein production in various biological contexts. Here, we use Ribo-seq and RNA-seq to show that genes related to oxidative phosphorylation are translationally downregulated during heart regeneration. We find that Nat10 regulates the expression of Uqcr11 and Uqcrb mRNAs in mouse and human cardiomyocytes. In mice, overexpression of Nat10 in cardiomyocytes promotes cardiac regeneration and improves cardiac function after injury. Conversely, treating neonatal mice with Remodelin-a Nat10 pharmacological inhibitor-or genetically removing Nat10 from their cardiomyocytes both inhibit heart regeneration. Mechanistically, Nat10 suppresses the expression of Uqcr11 and Uqcrb independently of its ac4C enzyme activity. This suppression weakens mitochondrial respiration and enhances the glycolytic capacity of the cardiomyocytes, leading to metabolic reprogramming. We also observe that the expression of Nat10 is downregulated in the cardiomyocytes of P7 male pig hearts compared to P1 controls. The levels of Nat10 are also lower in female human failing hearts than non-failing hearts. We further identify the specific binding regions of Nat10, and validate the pro-proliferative effects of Nat10 in cardiomyocytes derived from human embryonic stem cells. Our findings indicate that Nat10 is an epigenetic regulator during heart regeneration and could potentially become a clinical target.

Internet of things-based management versus standard management of home noninvasive ventilation in COPD patients with hypercapnic chronic respiratory failure: a multicentre randomized controlled non-inferiority trial.

Background: Effective monitoring and management are crucial during long-term home noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic chronic obstructive pulmonary disease (COPD). This study investigated the benefit of Internet of Things (IOT)-based management of home NPPV. Methods: This multicenter, prospective, parallel-group, randomized controlled non-inferiority trial enrolled patients requiring long-term home NPPV for hypercapnic COPD. Patients were randomly assigned (1:1), via a computer-generated randomization sequence, to standard home management or IOT management based on telemonitoring of clinical and ventilator parameters over 12 months. The intervention was unblinded, but outcome assessment was blinded to management assignment. The primary outcome was the between-group comparison of the change in health-related quality of life, based on severe respiratory insufficiency questionnaire scores with a non-inferiority margin of -5. This study is registered with Chinese Clinical Trials Registry (No. ChiCTR1800019536). Findings: Overall, 148 patients (age: 72.7 ± 6.8 years; male: 85.8%; forced expiratory volume in 1 s: 0.7 ± 0.3 L; PaCO2: 66.4 ± 12.0 mmHg), recruited from 11 Chinese hospitals between January 24, 2019, and June 28, 2021, were randomly allocated to the intervention group (n = 73) or the control group (n = 75). At 12 months, the mean severe respiratory insufficiency questionnaire score was 56.5 in the intervention group and 50.0 in the control group (adjusted between-group difference: 6.26 [95% CI, 3.71-8.80]; P < 0.001), satisfying the hypothesis of non-inferiority. The 12-month risk of readmission was 34.3% in intervention group compared with 56.0% in the control group, adjusted hazard ratio of 0.56 (95% CI, 0.34-0.92; P = 0.023). No severe adverse events were reported. Interpretation: Among stable patients with hypercapnic COPD, using IOT-based management for home NPPV improved health-related quality of life and prolonged the time to readmission. Funding: Air Liquide Healthcare (Beijing) Co., Ltd.

Utility of auto fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions.

BACKGROUND: Bronchoscopy is currently the most common technique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. METHODS: We conducted a retrospective study in a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions. RESULTS: A total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3 % (95 % confidence interval [CI]: 53.1 %-67.1 %), which was higher than that of patients with WLB alone (45.2 %, 95 % CI: 38.2-52.4 %) (P = 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100 %, 95 % CI: 95.5-100 % versus 69.6 %, 95 % CI: 59.6-78.1 %), positive predictive value (100 %, 95 % CI: 96.1-100 % versus 74.3 %, 95 % CI: 65.5-81.7 %) and negative predictive value (56.3 %, 95 % CI: 48.8-63.6 % versus 39.4 %, 95 % CI: 32.3-47.0 %). CONCLUSION: Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions.

Enhancing Hydrogen Evolution Reaction Activity of Palladium Catalyst by Immobilization on MXene Nanosheets.

Efficient catalysts with minimal content of catalytically active noble metals are essential for the transition to the clean hydrogen economy. Catalyst supports that can immobilize and stabilize catalytic nanoparticles and facilitate the supply of electrons and reactants to the catalysts are needed. Being hydrophilic and more conductive compared with carbons, MXenes have shown promise as catalyst supports. However, the controlled assembly of their 2D sheets creates a challenge. This study established a lattice engineering approach to regulate the assembly of exfoliated Ti3C2Tx MXene nanosheets with guest cations of various sizes. The enlargement of guest cations led to a decreased interlayer interaction of MXene lamellae and increased surface accessibility, allowing intercalation of Pd nanoparticles. Stabilization of Pd nanoparticles between interlayer-expanded MXene nanosheets improved their electrocatalytic activity. The Pd-immobilized K+-intercalated MXene nanosheets (PdKMX) demonstrated exceptional electrocatalytic performance for the hydrogen evolution reaction with the lowest overpotential of 72 mV (@10 mA cm-2) and the highest turnover frequency of 1.122 s-1 (@ an overpotential of 100 mV), which were superior to those of the state-of-the-art Pd nanoparticle-based electrocatalysts. Weakening of the interlayer interaction during self-assembly with K+ ions led to fewer layers in lamellae and expansion of the MXene in the c direction during Pd anchoring, providing numerous surface-active sites and promoting mass transport. In situ spectroscopic analysis suggests that the effective interfacial electron injection from the Pd nanoparticles strongly immobilized on interlayer-expanded PdKMX may be responsible for the improved electrocatalytic performance.

Clinical prediction models for knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To identify and describe existing models for predicting knee pain in patients with knee osteoarthritis. METHODS: The electronic databases PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library were searched from their inception to May 2023 for any studies to develop and validate a prediction model for predicting knee pain in patients with knee osteoarthritis. Two reviewers independently screened titles, abstracts, and full-text qualifications, and extracted data. Risk of bias was assessed using the PROBAST. Data extraction of eligible articles was extracted by a data extraction form based on CHARMS. The quality of evidence was graded according to GRADE. The results were summarized with descriptive statistics. RESULTS: The search identified 2693 records. Sixteen articles reporting on 26 prediction models were included targeting occurrence (n = 9), others (n = 7), progression (n = 5), persistent (n = 2), incident (n = 1), frequent (n = 1), and flares (n = 1) of knee pain. Most of the studies (94%) were at high risk of bias. Model discrimination was assessed by the AUROC ranging from 0.62 to 0.81. The most common predictors were age, BMI, gender, baseline pain, and joint space width. Only frequent knee pain had a moderate quality of evidence; all other types of knee pain had a low quality of evidence. CONCLUSION: There are many prediction models for knee pain in patients with knee osteoarthritis that do show promise. However, the clinical extensibility, applicability, and interpretability of predictive tools should be considered during model development.

Atomically-Thin Holey 2D Nanosheets of Defect-Engineered MoN-Mo5 N6 Composites as Effective Hybridization Matrices.

The defect engineering of inorganic solids has received significant attention because of its high efficacy in optimizing energy-related functionalities. Consequently, this approach is effectively leveraged in the present study to synthesize atomically-thin holey 2D nanosheets of a MoN-Mo5 N6 composite. This is achieved by controlled nitridation of assembled MoS2 monolayers, which induced sequential cation/anion migration and a gradual decrease in the Mo valency. Precise control of the interlayer distance of the MoS2 monolayers via assembly with various tetraalkylammonium ions is found to be crucial for synthesizing sub-nanometer-thick holey MoN-Mo5 N6 nanosheets with a tunable anion/cation vacancy content. The holey MoN-Mo5 N6 nanosheets are employed as efficient immobilization matrices for Pt single atoms to achieve high electrocatalytic mass activity, decent durability, and low overpotential for the hydrogen evolution reaction (HER). In situ/ex situ spectroscopy and density functional theory (DFT) calculations reveal that the presence of cation-deficient Mo5 N6 domain is crucial for enhancing the interfacial interactions between the conductive molybdenum nitride substrate and Pt single atoms, leading to enhanced electron injection efficiency and electrochemical stability. The beneficial effects of the Pt-immobilizing holey MoN-Mo5 N6 nanosheets are associated with enhanced electronic coupling, resulting in improvements in HER kinetics and interfacial charge transfer.

A polysaccharide from Alhagi honey protects the intestinal barrier and regulates the Nrf2/HO-1-TLR4/MAPK signaling pathway to treat alcoholic liver disease in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine, the main factors related to alcoholic liver disease (ALD) are qi stagnation and blood stasis of the five viscera. Previously, we showed that the bioactive components of Alhagi honey have various pharmacological effects in treating liver diseases, but the influence of Alhagi honey on ALD (and its mechanism of action) is not known. AIM OF THE STUDY: To determine the efficacy of the main active component of Alhagi honey, the polysaccharide AHPN80, in ALD and to explore the potential mechanism of action. MATERIALS AND METHODS: AHPN80 was isolated from dried Alhagi honey and identified by transmission electron microscopy, Fourier-transform infrared spectroscopy, and gas chromatography. Venous blood, liver tissue, and colon tissue were collected in a mouse model of alcohol-induced acute liver injury. Histology, staining (Oil Red O, Alcian Blue-Periodic Acid Schiff) and measurement of reactive oxygen species (ROS) levels were used to detect histopathologic and lipid-accumulation changes in the liver and colon. Lipopolysaccharide (LPS) levels and the content of proinflammatory cytokines in serum were measured by enzyme-linked immunosorbent assays. Commercial kits were employed to detect biochemistry parameters in serum and the liver. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining kit was used to identify hepatocyte apoptosis. Expression of tight junction-associated proteins in colon tissues and nuclear factor erythroid 2-related factor 2/heme oxygenase-1/toll-like receptor-4/mitogen-activated protein kinase (Nrf2/HO-1/TLR4/MAPK) pathway-related proteins in liver tissues and HepG2 cells were analyzed by immunofluorescence or western blotting. RESULTS: In a mouse model of alcohol-induced acute liver injury, AHPN80 therapy: significantly improved liver parameters (cytochrome P450 2E1, alcohol dehydrogenase, aldehyde dehydrogenase, superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, total cholesterol, triglycerides, alanine transaminase, aspartate transaminase); reduced serum levels of LPS, interleukin (IL)-1ß, IL-6, and tumor necrosis faction-α; increased levels of IL-10 and interferon-gamma. AHPN80 reduced ALD-induced lipid accumulation and ROS production, improved alcohol-induced inflammatory damage to hepatocytes, and inhibited hepatocyte apoptosis. Immunofluorescence staining and western blotting suggested that AHPN80 might eliminate hepatic oxidative stress by activating the Nrf2/HO-1 signaling pathway, repair the intestinal barrier, inhibit the LPS/TLR4/MAPK signaling pathway, and reduce liver inflammation. CONCLUSIONS: AHPN80 may activate the Nrf2/HO-1 pathway to eliminate oxidative stress, protect the intestinal barrier, and regulate the TLR4/MAPK pathway to treat ALD in mice. AHPN80 could be a functional food and natural medicine to prevent ALD and its complications.