The newly proposed plasma-glycosylated hemoglobin A1c/High-Density lipoprotein cholesterol ratio serves as a simple and practical indicator for screening metabolic associated fatty liver disease: an observational study based on a physical examination population.

BACKGROUND: Glycotoxicity and lipotoxicity are key pathophysiological mechanisms underlying the development of metabolic associated fatty liver disease (MAFLD). The primary objective of this study is to investigate the association between the newly proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein Cholesterol Ratio (HbA1c/HDL-C ratio) and the risk of MAFLD. METHODS: A study population of 14,251 individuals undergoing health examinations was included. The association between the HbA1c/HDL-C ratio and MAFLD was analyzed using multivariable logistic regression and restricted cubic spline (RCS) analysis. Exploratory analyses were conducted to assess variations in this association across subgroups stratified by gender, age, body mass index (BMI), exercise habits, drinking status, and smoking status. The discriminatory value of the HbA1c/HDL-C ratio and its components for screening MAFLD was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 1,982 (13.91%) subjects were diagnosed with MAFLD. After adjusting for confounding factors, we found a significant positive association between the HbA1c/HDL-C ratio and MAFLD [odds ratio (OR) 1.34, 95% confidence interval (CI): 1.25, 1.44]. No significant differences in this association were observed across all subgroups (All P for interaction > 0.05). Furthermore, through RCS analysis, we observed a nonlinear positive correlation between the HbA1c/HDL-C ratio and MAFLD (P for non-linearity < 0.001), with a potential threshold effect point (approximately 3 for the HbA1c/HDL-C ratio). Beyond this threshold point, the slope of the MAFLD prevalence curve increased rapidly. Additionally, in further ROC analysis, we found that for the identification of MAFLD, the HbA1c/HDL-C ratio was significantly superior to HbA1c and HDL-C, with an area under the curve (AUC) and optimal threshold of 0.81 and 4.08, respectively. CONCLUSIONS: Our findings suggest that the newly proposed HbA1c/HDL-C ratio serves as a simple and practical indicator for assessing MAFLD, exhibiting well-discriminatory performance in screening for MAFLD.

Genomic structural variants analysis in leukemia by a novel cytogenetic technique: Optical genome mapping.

Genomic structural variants (SVs) play a pivotal role in driving the evolution of hematologic malignancies, particularly in leukemia, in which genetic abnormalities are crucial features. Detecting SVs is essential for achieving precise diagnosis and prognosis in these cases. Karyotyping, often complemented by fluorescence in situ hybridization and/or chromosomal microarray analysis, provides standard diagnostic outcomes for various types of SVs in front-line testing for leukemia. Recently, optical genome mapping (OGM) has emerged as a promising technique due to its ability to detect all SVs identified by other cytogenetic methods within one single assay. Furthermore, OGM has revealed additional clinically significant SVs in various clinical laboratories, underscoring its considerable potential for enhancing front-line testing in cases of leukemia. This review aims to elucidate the principles of conventional cytogenetic techniques and OGM, with a focus on the technical performance of OGM and its applications in diagnosing and prognosticating myelodysplastic syndromes, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphocytic leukemia.

Nanoporous Titanium Implant Surface Accelerates Osteogenesis via the Piezo1/Acetyl-CoA/ß-Catenin Pathway.

Osseointegration is the most important factor determining implant success. The surface modification of TiO2 nanotubes prepared by anodic oxidation has remarkable advantages in promoting bone formation. However, the mechanism behind this phenomenon is still unintelligible. Here we show that the nanomorphology exhibited open and clean nanotube structure and strong hydrophilicity, and the nanomorphology significantly facilitated the adhesion, proliferation, and osteogenesis differentiation of stem cells. Exploring the mechanism, we found that the nanomorphology can enhance mitochondrial oxidative phosphorylation (OxPhos) by activating Piezo1 and increasing intracellular Ca2+. The increase in OxPhos can significantly uplift the level of acetyl-CoA in the cytoplasm but not significantly raise the level of acetyl-CoA in the nucleus, which was beneficial for the acetylation and stability of ß-catenin and ultimately promoted osteogenesis. This study provides a new interpretation for the regulatory mechanism of stem cell osteogenesis by nanomorphology.

[Analysis of Regional Differences in Cadmium Ecological Risk in Surface Waters of the Yangtze River Basin].

This study primarily focused on the regional disparities in both water quality criteria and ecological risks attributed to cadmium presence within the surface waters of the Yangtze River Basin. In the initial phase, the long-term water quality criteria for cadmium were recalibrated in accordance with the guidelines outlined in China's "Water Quality Criteria for Freshwater Aquatic Organisms-Cadmium," accounting for the prevalent hardness distribution within the Yangtze River Basin's surface water. Subsequently, a more refined revision was undertaken considering the specific characteristics of the species residing within the Yangtze River Basin. This undertaking led to a comprehensive interpretation of the regional variations in both the distribution of long-term water quality criteria values and the risk quotient distribution of cadmium throughout the Yangtze River Basin. The incorporation of hardness and species-specific attributes resulted in a revised range of long-term water quality criteria for cadmium across different urban locales within the Yangtze River Basin. Notably, the recalibrated values ranged from 0.08 µg·L-1 as the lowest threshold to 0.75 µg·L-1 as the upper limit, signifying a tenfold differentiation. Correspondingly, the urban average annual risk quotient associated with cadmium exposure demonstrated a variation from 0.035 to 1.12, marking a significant 32-fold discrepancy between the lowest and highest values. It is essential to highlight that regions of paramount importance, such as the confluence area connecting the upper and middle stretches of the Yangtze River Basin and the intricate Dongting Lake system, exhibited noteworthy ecological risks attributed to cadmium presence. Consequently, further in-depth investigations into these critical regions are imperative for a comprehensive understanding of the associated risks.

Investigate the potential impact of Hemagglutinin from the H1N1 strain on severe pneumonia.

The most prevalent glycoprotein on the influenza virus envelope is called hemagglutinin (HA), yet little is known about its involvement in the pathophysiology and etiology of severe influenza pneumonia. Here, after stimulating human bronchial epithelial cells (16-HBE) and mice with HA of H1N1 for 12 h, we investigated the proliferation, migration, inflammatory cytokines expression, and apoptosis in 16-HBE and the pathological damage in mouse lung tissue. The expression of inflammatory cytokines plasminogen activator inhibitor 1(PAI-1), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators, and apoptosis were all enhanced by HA, which also prevented the proliferation and migration of bronchial epithelial cells. HA enhanced up-regulated PAI-1, uPA, and tPA protein expression within mouse lung tissue and caused lung injury. In conclusion, HA alone, but not the whole H1N1 virus, induces lung tissue injury by inhibiting cell proliferation and migration, while promoting the expression of inflammatory cytokines and apoptosis.

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups.

INTRODUCTION: Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. In the SURPASS-AP-Combo trial, once-weekly tirzepatide was associated with improved glycemic control and weight loss versus insulin glargine and was generally well tolerated in an Asia-Pacific, predominately Chinese, population with type 2 diabetes (T2D). This post hoc subgroup analysis of SURPASS-AP-Combo assessed the potential influence of patient baseline characteristics on the efficacy and safety of tirzepatide. METHODS: Changes from baseline to week 40 in HbA1c, body weight, fasting serum glucose (FSG), and daily glucose average from self-measured blood glucose profiles were analyzed by potential influential factors including age (< 65, ≥ 65 years), sex, baseline HbA1c (≤ 8.5, > 8.5%), body mass index (BMI) (< 25, ≥ 25 kg/m2), body weight (< 75, ≥ 75 kg), duration of diabetes (< 10, ≥ 10 years), and concomitant oral antihyperglycemic medications (metformin, metformin plus sulphonylurea). Gastrointestinal adverse events and hypoglycemia were also evaluated. RESULTS: At week 40, all tirzepatide doses were associated with reduced HbA1c, body weight, FSG, and daily glucose average from baseline in all subgroups. Greater HbA1c reductions were achieved in patients with higher baseline HbA1c across all tirzepatide doses, higher body weight with 10 mg and younger age with 15 mg tirzepatide. Greater reductions in body weight were observed in patients with higher body weight across all tirzepatide doses, lower baseline HbA1c with 5 mg and higher BMI with 5 mg tirzepatide. CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with reduced blood glucose and body weight in a predominantly Chinese population with T2D across different subgroups, consistent with previous reports for tirzepatide. CLINICAL TRIAL REGISTRATION: NCT04093752.

Synergetic approaches of fucoidan and trabectedin complex coated PLGA nanoparticles effectively suppresses proliferation and induce apoptosis for the treatment on non-small cell lung cancer.

Traditional methods of treating lung cancer have not been very effective, contributing to the disease's high incidence and death rate. As a result, Fn/Tn-PLGA NPs, a novel directed fucoidan and trabectedin complex loaded PLGA nanoparticle, were produced to investigate the role of developing therapeutic strategies for NSCLC and A549 cell lines. Quantitative real-time polymerase chain reaction was used to examine protein expression and mRNA expression, respectively. Protein activity was knocked down using specific inhibitors and short disrupting RNA transfection. Lastly, cancer cell lines H1299 and A549 were subjected to an in vitro cytotoxicity experiment. Commercial assays were used to assess the levels of cell viability, ROS and proliferation found that Fn/Tn-PLGA NPs effectively killed lung cancer cells. To examine cell death, annexin flow cytometry was employed. In addition, a scratch-wound assay was conducted to assess the migration effects of Fn/Tn-PLGA NPs in a laboratory setting. Finally, PLGA NPs covered with a mix of fucoidan and trabectedin could be a good vehicle for targeting cancerous tissues with chemotherapeutic drugs.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer.

OBJECTIVE: This study aimed to investigate the changes of follicular helper T (TFH) and follicular regulatory T (TFR) cell subpopulations in patients with non-small cell lung cancer (NSCLC) and their significance. METHODS: Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls. Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1 (PD-1) and inducible co-stimulator (ICOS), and TFR cell subpopulation based on cluster determinant 45RA (CD45RA) and forkhead box protein P3 (FoxP3). The levels of interleukin-10 (IL-10), interleukin-17a (IL-17a), interleukin-21 (IL-21), and transforming growth factor-ß (TGF-ß) in the plasma were measured, and changes in circulating B cell subsets and plasma IgG levels were also analyzed. The correlation between serum cytokeratin fragment antigen 21-1 (CYFRA 21-1) levels and TFH, TFR, or B cell subpopulations was further explored. RESULTS: The TFR/TFH ratio increased significantly in NSCLC patients. The CD45RA+FoxP3int TFR subsets were increased, with their proportions increasing in stages II to III and decreasing in stage IV. PD-1+ICOS+TFH cells showed a downward trend with increasing stages. Plasma IL-21 and TGF-ß concentrations were increased in NSCLC patients compared with healthy controls. Plasmablasts, plasma IgG levels, and CD45RA+FoxP3int TFR cells showed similar trends. TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages I-III and negatively correlated with CYFRA 21-1 in stage IV. CONCLUSION: Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC, which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.

Human papillomavirus (HPV)-induced oropharyngeal cancer now exceeds HPV-induced cervical cancer, with a noticeable sex bias. Although it is well established that women have a more proficient immune system, it remains unclear whether immune control of oral papillomavirus infections differs between sexes. In the current study, we use genetically modified mice to target CCR2 and Stat1 pathways, with the aim of investigating the role of both innate and adaptive immune responses in clearing oral papillomavirus, using our established papillomavirus (MmuPV1) infection model. Persistent oral MmuPV1 infection was detected in Rag1ko mice with T and B cell deficiencies. Meanwhile, other tested mice were susceptible to MmuPV1 infections but were able to clear the virus. We found sex differences in key myeloid cells, including macrophages, neutrophils, and dendritic cells in the infected tongues of wild type and Stat1ko mice but these differences were not observed in CCR2ko mice. Intriguingly, we also observed a sex difference in anti-MmuPV1 E4 antibody levels, especially for two IgG isotypes: IgG2b and IgG3. However, we found comparable numbers of interferon-gamma-producing CD8 T cells stimulated by E6 and E7 in both sexes. These findings suggest that males and females may use different components of innate and adaptive immune responses to control papillomavirus infections in the MmuPV1 mouse model. The observed sex difference in immune responses, especially in myeloid cells including dendritic cell (DC) subsets, may have potential diagnostic and prognostic values for HPV-associated oropharyngeal cancer.

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

Anterior temporal lobectomy improved mood status and quality of life in Chinese patients with mesial temporal lobe epilepsy: a single-arm cohort study.

BACKGROUND: Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function; whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE. METHODS: This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery. RESULTS: Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P   >  0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. CONCLUSIONS: Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.

miR-4757-3p Inhibited the Migration and Invasion of Lung Cancer Cell via Targeting Wnt Signaling Pathway.

Lung cancer accounts for the vast majority of cancer-related deaths worldwide, and aberrant miRNA expression is commonly observed as the disease progresses. The current study aimed to determine the role of miR-4757-3p in the development of lung cancer. The real-time PCR test was performed to determine the expression of miR-4757-3p in lung cancer cell lines. miR-4757-3p was downregulated in A549 cells. CCK8 and transwell assays demonstrated that overexpression of miR-4757-3p significantly reduced A549 cell invasion and migration. Bioinformatic analysis by the TargetScan database predicted the possible targets of miR-4757-3p. A luciferase activity test was used to determine the direct relationship between miR-4757-3p, Wnt5a, and Wnt8b. The overexpression of miR-4757-3p drastically inhibited the expression of Wnt5a and Wnt8b. Furthermore, we discovered that silencing Wnt5a and Wnt8b significantly lowered ß-catenin expression and hampered invasion and migration. Finally, miR-4757-3p inhibited lung cancer cell migration and invasion by inhibiting the activation of the Wnt signaling pathway. Our study provided evidence that miR-4757-3p could be developed as an indicator or an anticancer target in the clinical application.

Recent Advances in the Enzyme-Activatable Organic Fluorescent Probes for Tumor Imaging and Therapy.

The exploration of advanced probes for cancer diagnosis and treatment is of high importance in fundamental research and clinical practice. In comparison with the traditional "always-on" probes, the emerging activatable probes enjoy advantages in promoted accuracy for tumor theranostics by specifically releasing or activating fluorophores at the targeting sites. The main designing principle for these probes is to incorporate responsive groups that can specifically react with the biomarkers (e. g., enzymes) involved in tumorigenesis and progression, realizing the controlled activation in tumors. In this review, we summarize the latest advances in the molecular design and biomedical application of enzyme-responsive organic fluorescent probes. Particularly, the fluorophores can be endowed with ability of generating reactive oxygen species (ROS) to afford the photosensitizers, highlighting the potential of these probes in simultaneous tumor imaging and therapy with rational design. We hope that this review could inspire more research interests in the development of tumor-targeting theranostic probes for advanced biological studies.

Passive Immunization with a Single Monoclonal Neutralizing Antibody Protects against Cutaneous and Mucosal Mouse Papillomavirus Infections.

We have established a mouse papillomavirus (MmuPV1) model that induces both cutaneous and mucosal infections and cancers. In the current study, we use this model to test our hypothesis that passive immunization using a single neutralizing monoclonal antibody can protect both cutaneous and mucosal sites at different time points after viral inoculation. We conducted a series of experiments involving the administration of either a neutralizing monoclonal antibody, MPV.A4, or control monoclonal antibodies to both outbred and inbred athymic mice. Three clinically relevant mucosal sites (lower genital tract for females and anus and tongue for both males and females) and two cutaneous sites (muzzle and tail) were tested. At the termination of the experiments, all tested tissues were harvested for virological analyses. Significantly lower levels of viral signals were detected in the MPV.A4-treated female mice up to 6 h post-viral inoculation compared to those in the isotype control. Interestingly, males displayed partial protection when they received MPV.A4 at the time of viral inoculation, even though they were completely protected when receiving MPV.A4 at 24 h before viral inoculation. We detected MPV.A4 in the blood starting at 1 h and up to 8 weeks postadministration in some mice. Parallel to these in vivo studies, we conducted in vitro neutralization using a mouse keratinocyte cell line and observed complete neutralization up to 8 h post-viral inoculation. Thus, passive immunization with a monoclonal neutralizing antibody can protect against papillomavirus infection at both cutaneous and mucosal sites and is time dependent. IMPORTANCE This is the first study testing a single monoclonal neutralizing antibody (MPV.A4) by passive immunization against papillomavirus infections at both cutaneous and mucosal sites in the same host in the mouse papillomavirus model. We demonstrated that MPV.A4 administered before viral inoculation can protect both male and female athymic mice against MmuPV1 infections at cutaneous and mucosal sites. MPV.A4 also offers partial protection at 6 h post-viral inoculation in female mice. MPV.A4 can be detected in the blood from 1 h to 8 weeks after intraperitoneal (i.p.) injection. Interestingly, males were only partially protected when they received MPV.A4 at the time of viral inoculation. The failed protection in males was due to the absence of neutralizing MPV.A4 at the infected sites. Our findings suggest passive immunization with a single monoclonal neutralizing antibody can protect against diverse papillomavirus infections in a time-dependent manner in mice.

miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis.

The aim of this study was to verify the biological function of miR-1273h-5p in gastric cancer (GC) and its underlying mechanisms. The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected using microarrays, miR-1273h-5p, and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA, and protein levels were evaluated using polymerase chain reaction and Western blotting methods, cell proliferation, apoptosis, migration, and invasion were determined by CCK-8, flow cytometry, and transwell assay. Compared to tumor-adjacent normal tissue and gastric epithelial mucosa cell line cells, miR-1273h-5p was significantly downregulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant upregulation of CXCL12 was observed when the miR-1273h-5p was downregulated in GC cells. Additionally, miR-1273h-5p significantly reduces tumor volume and weight. Thus, this study suggests that miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3'-untranslational regions, which may be a novel diagnostic and therapeutic target in GC.

MiR-146a expression profiles in osteoarthritis in different tissue sources: a meta-analysis of observational studies.

BACKGROUND: MiR-146a has been widely studied in the pathogenesis of osteoarthritis (OA); however, the results are still controversial. OBJECTIVE: This meta-analysis analyzes the expression profile of miR-146a in various tissues of OA patients. METHODS: Public databases were searched for appropriate studies published up to September 1, 2021. A case-control study comparing the OA population and a non-OA healthy population was included. RESULTS: 26 articles were included in analysis. The results showed that the expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly higher in OA patients than in controls (SMD: 1.23; 95% CI 0.08-2.37; p = 0.035) but not in plasma (SMD: 1.09; 95% CI - 0.06, 2.24; p = 0.064). The expression level of miR-146a in cartilage was also significantly higher in OA patients than in controls (SMD: 6.39; 95% CI 0.36, 12.4; p = 0.038) but not in chondrocytes (SMD: - 0.71; 95% CI - 4.15, 2.73; p = 0.687). The miR-146a level was significantly lower in synoviocytes in the OA population than in control patients (SMD: - 0.97; 95% CI - 1.68, - 0.26; p = 0.008). In synovial tissue, synovial fluid, and regulatory T cells, there was no significant difference. CONCLUSION: The expression level of miR-146a in cartilage tissue and PBMCs was significantly higher in OA patients than in non-OA healthy controls. Due to the limitations of this study, more research is needed to confirm these results in the future. TRIAL REGISTRATION: retrospectively registered.

Type I macrophage activator photosensitizer against hypoxic tumors.

Photodynamic immunotherapy has emerged as a promising strategy to treat cancer. However, the hypoxic nature of most solid tumors and notoriously immunosuppressive tumor microenvironment could greatly compromise the efficacy of photodynamic immunotherapy. To address this challenge, we rationally synthesized a type I photosensitizer of TPA-DCR nanoparticles (NPs) with aggregation-enhanced reactive oxygen species generation via an oxygen-independent pathway. We demonstrated that the free radicals produced by TPA-DCR NPs could reprogram M0 and M2 macrophages into an anti-tumor state, which is not restricted by the hypoxic conditions. The activated M1 macrophages could further induce the immunogenic cell death of cancer cells by secreting pro-inflammatory cytokines and phagocytosis. In addition, in vivo anti-tumor experiments revealed that the TPA-DCR NPs could further trigger tumor immune response by re-educating tumor-associated macrophages toward M1 phenotype and promoting T cell infiltration. Overall, this work demonstrates the design of type I organic photosensitizers and mechanistic investigation of their superior anti-tumor efficacy. The results will benefit the exploration of advanced strategies to regulate the tumor microenvironment for effective photodynamic immunotherapy against hypoxic tumors.

Targeted NIR-II emissive nanoprobes for tumor detection in mice and rabbits.

The functional NIR-II emissive nanoprobe loaded with AIEgen (cRGD-TTB NPs) achieved a high quantum yield (10.32%) and a high signal-to-background (S/B) ratio of 7.7 when employed for the visualization of large tumors (∼600 mm3) in rabbit models for the first time. This work will aid in the investigation of tumor targeting effect of therapeutic agents in large animal models.

Strain localisation and failure at twin-boundary complexions in nickel-based superalloys.

Twin boundaries (TBs) in Ni-based superalloys are vulnerable sites for failure in demanding environments, and a current lack of mechanistic understanding hampers the reliable lifetime prediction and performance optimisation of these alloys. Here we report the discovery of an unexpected γ″ precipitation mechanism at TBs that takes the responsibility for alloy failure in demanding environments. Using multiscale microstructural and mechanical characterisations (from millimetre down to atomic level) and DFT calculations, we demonstrate that abnormal γ″ precipitation along TBs accounts for the premature dislocation activities and pronounced strain localisation associated with TBs during mechanical loading, which serves as a precursor for crack initiation. We clarify the physical origin of the TBs-related cracking at the atomic level of γ″-strengthened Ni-based superalloys in a hydrogen containing environment, and provide practical methods to mitigate the adverse effect of TBs on the performance of these alloys.