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Abstract Myocardial infarction accompanied by diabetes mellitus is accepted as the most serious type of coronary heart disease, and among the current treatment strategies, the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge. In this study, we developed a biodegradable nanoparticles‐based delivery system with excellent macrophage escape, cardiac targeting, and drug release properties to achieve targeted therapy of myocardial infarction. Specifically, a copolymer of p(DMA–MPC–CD) combining self‐adhesion, hydration lubrication, and targeting peptide binding site was successfully prepared by free radical copolymerization, and it was self‐assembled on the surface of melatonin‐loaded dendritic mesoporous silica nanoparticles (bMSNs) following the integration of adamantane‐modified cardiac homing peptide (CHP) based on supramolecular host–guest interaction. Importantly, a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles, which was confirmed by the enhancement in hydration lubrication and reduction in coefficient of friction, prevented the nanoparticles from phagocytosis by the macrophages. The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capability, and the in vivo mice study demonstrated that the intravenous injection of drug‐loaded nanoparticles (namely bMSNs–Mel@PDMC–CHP) effectively reduced cardiomyocyte apoptosis, alleviated myocardial interstitial fibrosis, and enhanced cardiac function.

Abstract Aims This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). Methods and results We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end‐diastolic volume index (LVEDVI), and left ventricular end‐systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow‐up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non‐ST‐elevation myocardial infarction (NSTEMI) group, and ST‐elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT‐proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT‐proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P

Abstract Animals living in high‐altitude environments, such as the Tibetan Plateau, must face harsh environmental conditions (e.g., hypoxia, cold, and strong UV radiation). These animals' physiological adaptations (e.g., increased red cell production and turnover rate) might also be associated with the gut microbial response. Bilirubin is a component of red blood cell turnover or destruction and is excreted into the intestine and reduced to urobilinoids and/or urobilinogen by gut bacteria. Here, we found that the feces of macaques living in high‐altitude regions look significantly browner (with a high concentration of stercobilin, a component from urobilinoids) than those living in low‐altitude regions. We also found that gut microbes involved in urobilinogen reduction (e.g., beta‐glucuronidase) were enriched in the high‐altitude mammal population compared to the low‐altitude population. Moreover, the spatial–temporal change in gut microbial function was more profound in the low‐altitude macaques than in the high‐altitude population, which might be attributed to profound changes in food resources in the low‐altitude regions. Therefore, we conclude that a high‐altitude environment's stress influences living animals and their symbiotic microbiota.

Abstract Climate change and nutrient pollution contribute to the expanding global footprint of harmful algal blooms. To better predict their spatial distributions and disentangle biophysical controls, a novel Lagrangian particle tracking and biological (LPT‐Bio) model was developed with a high‐resolution numerical model and remote sensing. The LPT‐Bio model integrates the advantages of Lagrangian and Eulerian approaches by explicitly simulating algal bloom dynamics, algal biomass change, and diel vertical migrations along predicted trajectories. The model successfully captured the intensity and extent of the 2020 Margalefidinium polykrikoides bloom in the lower Chesapeake Bay and resolved fine‐scale structures of bloom patchiness, demonstrating a reliable prediction skill for 7–10 d. The fully coupled LPT‐Bio model initialized/calibrated by remote sensing and controlled by ambient environmental conditions appeared to be a powerful approach to predicting transport pathways, identifying bloom hotspots, resolving concentration variations at subgrid scales, and investigating responses of HABs to changing environmental conditions and human interference.

Abstract As one of the most destructive pests, aphids cause significant damage on various agricultural and horticultural crops. Recently, melatonin has been shown to enhance plant resistance to aphids; however, the underlying mechanisms remain unclear. In this study, our results showed that melatonin, MeJA, and H2S enhanced aphid resistance of watermelon in a dose‐dependent manner, accompanied by increases in the defense‐related enzyme activities and lignin accumulation. On the plants pretreated with 100 μM melatonin, 100 μM MeJA, and 50 μM NaHS, the numbers of aphids were 86.0%, 59.6%, and 47.9% lower than that on control plants, respectively, after aphid infestation for 7 days. Melatonin application induced MeJA and H2S accumulation in response to aphid infestation, while inhibition of MeJA and H2S accumulation attenuated or abolished melatonin‐induced defense response and aphid resistance, suggestive of the involvement of MeJA and H2S in melatonin‐induced aphid resistance. MeJA also increased H2S accumulation, but inhibition of MeJA biosynthesis prevented melatonin‐enhanced H2S accumulation, suggesting that MeJA mediates melatonin‐induced H2S accumulation. Furthermore, inhibition of H2S production attenuated MeJA‐induced defense response and aphid resistance. Taken together, the current study reveals a novel mechanism in which MeJA‐dependent H2S signaling is involved in melatonin‐induced defense response and subsequent aphid resistance. The increasing concern to minimize the use of pesticides and to switch onto sustainable and natural control strategies indicates the great exploitation of such a mechanism in combating aphids.

Abstract Most of the current bioadhesives cannot perform well on bleeding tissues while postoperative adhesion is a general but serious clinical issue. Here, a three‐layer biodegradable Janus tissue patch (J‐TP) that is able to simultaneously enable efficient closure of bleeding wounds with significantly promoted clotting ability and suppressed postoperative adhesion of tissues is reported. A dry adhesive hydrogel bottom layer of the J‐TP can form rapid (within 15 s) and strong (tensile strength up to 98 kPa) adhesion to bleeding/wet tissues with high bursting pressure (about 312.5 mmHg on a sealed porcine skin) through hydrogen binding and covalent conjugation between the carboxyl & N‐hydroxy succinimide (NHS) groups of hydrogel and the primary amine groups of tissues, while the phosphonic motifs can significantly reduce blood loss (by 81% on a rat bleeding liver model) of bleeding wounds. A thin polylactic acid (PLA) middle layer can improve the tensile strength (by 132%) of the J‐TP in wet conditions while the grafted zwitterionic polymers can effectively prevent postoperative tissue adhesion and inflammatory reaction. This J‐TP may be a promising tissue patch to assist the clinical treatment of injured bleeding tissues with inhibited postoperative adhesion.

Abstract Aim Current study was to evaluate relationship between baseline serum lipoprotein (a) [Lp(a)] level and prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and to explore whether the relationship would be modified by baseline high‐sensitivity C‐reactive protein (Hs‐CRP) level. Methods and results This is an observational prospective study. HFrEF patients from outpatient clinic were consecutively recruited (n = 362). Based on Lp(a) cutoff (30 mg/dL), patients were divided into normal and high Lp(a) groups; and based on Hs‐CRP cutoff (3 mg/dL), patients were divided into low‐degree and high‐degree groups. The 1 year rate of HF rehospitalization was similar between these two groups (22.7% vs. 24.1%, P = 0.18), while the 1 year rate of cardiovascular mortality was higher in Lp(a) ≥ 30 mg/dL versus Lp(a)

Abstract With the threat posed by drug‐resistant pathogenic bacteria, developing non‐antibiotic strategies for eradicating clinically prevalent superbugs remains challenging. Ferroptosis is a newly discovered form of regulated cell death that can overcome drug resistance. Emerging evidence shows the potential of triggering ferroptosis‐like for antibacterial therapy, but the direct delivery of iron species is inefficient and may cause detrimental effects. Herein, an effective strategy to induce bacterial nonferrous ferroptosis‐like by coordinating single‐atom metal sites (e.g., Ir and Ru) into the sp2‐carbon‐linked covalent organic framework (sp2c‐COF‐Ir‐ppy2 and sp2c‐COF‐Ru‐bpy2) is reported. Upon activating by light irradiation or hydrogen peroxide, the as‐constructed Ir and Ru single‐atom catalysts (SACs) can significantly expedite intracellular reactive oxygen species burst, enhance glutathione depletion‐related glutathione peroxidase 4 deactivation, and disturb the nitrogen and respiratory metabolisms, leading to lipid peroxidation‐driven ferroptotic damage. Both SAC inducers show potent antibacterial activity against Gram‐positive bacteria, Gram‐negative bacteria, clinically isolated methicillin‐resistant Staphylococcus aureus (MRSA), and biofilms, as well as excellent biocompatibility and strong therapeutic and preventive potential in MRSA‐infected wounds and abscesses. This delicate nonferrous ferroptosis‐like strategy may open up new insights into the therapy of drug‐resistant pathogen infection.

Abstract The response of tidal range in tidal marshes under sea‐level rise (SLR) is essential to the marsh resilience, but how tidal ranges respond to different marsh evolutions remains unclear. Here, we show the existence of bifurcate responses of tidal range to SLR using both numerical model and theoretical analyses. The tidal range tends to increase if marsh accretion keeps pace with SLR; otherwise, the tidal range tends to decrease. As tidal range plays the key role in marsh evolution, the interactions between changing tidal range and marsh evolution lead to positive feedback on marsh resilience. If the marsh accretion can keep up with the SLR, the increase in the tidal range can enhance marsh resilience to SLR. If the marsh cannot keep up, the decrease in the tidal range may further threaten the marsh resilience or even lead to marsh retreat.

Abstract Background The response to neoadjuvant chemotherapy (NAC) differs substantially among individual patients with non‐small cell lung cancer (NSCLC). Major pathological response (MPR) is a histomorphological read‐out used to assess treatment response and prognosis in patients NSCLC after NAC. Although spatial metabolomics is a promising tool for evaluating metabolic phenotypes, it has not yet been utilized to assess therapy responses in patients with NSCLC. We evaluated the potential application of spatial metabolomics in cancer tissues to assess the response to NAC, using a metabolic classifier that utilizes mass spectrometry imaging combined with machine learning. Methods Resected NSCLC tissue specimens obtained after NAC (n = 88) were subjected to high‐resolution mass spectrometry, and these data were used to develop an approach for assessing the response to NAC in patients with NSCLC. The specificities of the generated tumor cell and stroma classifiers were validated by applying this approach to a cohort of biologically matched chemotherapy‐naïve patients with NSCLC (n = 85). Results The developed tumor cell metabolic classifier stratified patients into different prognostic groups with 81.6% accuracy, whereas the stroma metabolic classifier displayed 78.4% accuracy. By contrast, the accuracies of MPR and TNM staging for stratification were 62.5% and 54.1%, respectively. The combination of metabolic and MPR classifiers showed slightly lower accuracy than either individual metabolic classifier. In multivariate analysis, metabolic classifiers were the only independent prognostic factors identified (tumor: P = 0.001, hazards ratio [HR] = 3.823, 95% confidence interval [CI] = 1.716–8.514; stroma: P = 0.049, HR = 2.180, 95% CI = 1.004–4.737), whereas MPR (P = 0.804; HR = 0.913; 95% CI = 0.445–1.874) and TNM staging (P = 0.078; HR = 1.223; 95% CI = 0.977–1.550) were not independent prognostic factors. Using Kaplan‐Meier survival analyses, both tumor and stroma metabolic classifiers were able to further stratify patients as NAC responders (P < 0.001) and non‐responders (P < 0.001). Conclusions Our findings indicate that the metabolic constitutions of both tumor cells and the stroma are valuable additions to the classical histomorphology‐based assessment of tumor response.

Abstract Developing solid‐state luminescent materials with bright long‐wavelength emissions is of considerable practical importance in light‐emitting diodes (LEDs) but remains a formidable challenge. Here, a novel structure engineering strategy is reported to realize solid‐state fluorescence (FL)‐emitted carbon dots (CDs) from visible to near‐infrared region. This is the first report of such an extended wavelength emission of self‐quenching‐resistant solid‐state CDs. Notably, the quantum yields of these CDs are remarkably improved up to 67.7%, which is the highest value for solid‐state CDs. The surface polymer chains of CDs can efficiently suppress the conjugated sp2 carbon cores from π–π stacking inducing aggregation caused FL quenching, and the redshift of FL emissions is attributed to narrowing bandgap caused by an enlarged sp2 carbon core. Using these CDs as conversion phosphors, the fabrication of white LEDs with adjustable correlated color temperatures of 1882–5019 K is achieved. Moreover, a plant growth LED device is assembled with a blue‐LED chip and deep‐red/near‐infrared‐emitted CDs. Compared with sunlight and white LEDs, the peanuts irradiated by plant growth LED lamp show higher growth efficiency in terms of branches and leaves. This work provides high‐quality solid‐state CD‐based phosphors for LED lighting sources that are required for diverse optoelectronic applications.

Abstract The presence of a new lumbar swelling or pain in the postoperative period following laparoscopic surgery should raise the suspicion of a lumbar hernia. Cross‐sectional imaging can be used to establish an early diagnosis to enable successful management.

Abstract Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti‐programmed death 1 (αPD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor β (TGF‐β). Using glutathione‐responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF‐β1 receptor, it is demonstrated that local inhibition of TGF‐β within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and αPD1 therapy, and induces long‐term antitumor memory. The therapeutic efficacy is also attributed to tumor infiltration by CD8+ cytotoxic T cells, depletion of regulatory T cells, and maturation of antigen‐presenting dendritic cells. Thus, modulating neutrophil polarization with nanomedicine is a promising strategy for treating pancreatic cancer.

Abstract The use of nanoparticles (NPs) to deliver small inhibiting microRNAs (miRNAs) has shown great promise for treating cancer. However, constructing a miRNA delivery system that targets brain cancers, such as glioblastoma multiforme (GBM), remains technically challenging due to the existence of the blood‐tumor barrier (BTB). In this work, a novel targeted antisense miRNA‐21 oligonucleotide (ATMO‐21) delivery system is developed for GBM treatment. Bradykinin ligand agonist‐decorated spermine‐modified acetalated dextran NPs (SpAcDex NPs) could temporarily open the BTB by activating G‐protein‐coupled receptors that are expressed in tumor blood vessels and tumor cells, which increase transportation to and accumulation in tumor sites. ATMO‐21 achieves high loading in the SpAcDex NPs (over 90%) and undergoes gradual controlled release with the degradation of the NPs in acidic lysosomal compartments. This allows for cell apoptosis and inhibition of the expression of vascular endothelial growth factor by downregulating hypoxia‐inducible factor (HIF‐1α) protein. An in vivo orthotopic U87MG glioma model confirms that the released ATMO‐21 shows significant therapeutic efficacy in inhibiting tumor growth and angiogenesis, demonstrating that agonist‐modified SpAcDex NPs represent a promising strategy for GBM treatment combining targeted gene therapy and antiangiogenic therapy.

Abstract Ehlers‐Danlos syndrome, specifically EDS4, can be a dangerous condition. Clinicians should be aware of this when referring such patients for any interventional procedure. An MDT approach should be adopted to help plan perioperative treatment and care.

Abstract Poor permeation of therapeutic agents and multidrug resistance (MDR) in solid tumors are the two major challenges that lead to the failure of the current chemotherapy methods. Herein, a zero‐waste doxorubicin‐loaded heparin/folic acid/l‐arginine (HFLA‐DOX) nanomotor with motion ability and sustained release of nitric oxide (NO) to achieve deep drug penetration and effective reversal of MDR in cancer chemotherapy is designed. The targeted recognition, penetration of blood vessels, intercellular penetration, special intracellular distribution (escaping from lysosomes and accumulating in Golgi and nucleus), 3D multicellular tumor spheroids (3D MTSs) penetration, degradation of tumor extracellular matrix (ECM), and reversal of MDR based on the synergistic effects of the motion ability and sustained NO release performance of the NO‐driven nanomotors are investigated in detail. Correspondingly, a new chemotherapy mode called recognition‐penetration‐reversal‐elimination is proposed, whose effectiveness is verified by in vitro cellular experiments and in vivo animal tumor model, which can not only provide effective solutions to these challenges encountered in cancer chemotherapy, but also apply to other therapy methods for the special deep‐tissue penetration ability of a therapeutic agent.

Abstract Background Lynch syndrome (LS) is an autosomal‐dominant disorder that increases the risk of many cancers. The genetic basis of LS is germline mutations in DNA mismatch repair genes. Methods We performed next‐generation sequencing on blood cells obtained from the members of three unrelated LS pedigrees. Immunohistochemistry staining was performed to analyze protein expression. Results Multigene panel screening revealed three mutL homolog 1 (MLH1) pathogenic mutations (c.199G>A, c.790 + 1G>A, and c.1557_1558 + 8delGGGTACGTAA, unreported) confirmed by Sanger sequencing. Immunohistochemistry showed a loss of MLH1 protein expression. We also confirmed that the unreported mutant allele was inherited for at least three generations. Conclusion These results provide new insights into the molecular mechanisms underlying the pathogenicity of MLH1 mutations and reaffirm the importance of genetic screening for the early diagnosis of LS.

Exosomes play a critical role in intercellular communication since they contain signalling molecules and genetic materials. During tumorigenesis, tumour-derived exosomes have been demonstrated to promote tumour angiogenesis and metastasis. However, how the exosomes facilitate tumour metastasis is not clear. Here we explored the effect of HeLa cell-derived exosomes (ExoHeLa) on endothelial tight junctions (TJ) and the related mechanisms. After human umbilical vein endothelial cells (HUVEC) were treated with ExoHeLa, TJ proteins zonula occludens-1 (ZO-1) and Claudin-5 in HUVEC were significantly reduced as compared with that treated with exosomes from human cervical epithelial cells, while mRNA levels of ZO-1 and Claudin-5 remained unchanged. Consequently, permeability of endothelial monolayer was increased after the treatment with ExoHeLa. Injection of ExoHeLa into mice also increased vascular permeability and tumour metastasis in vivo. Neither knocking down of Dicer nor use of inhibitors of microRNAs targeting at mRNAs of ZO-1 and Claudin-5 could block the inhibitory effect of ExoHeLa on ZO-1 and Claudin-5. The expression of genes involved in endoplasmic reticulum (ER) stress was significantly increased in HUVECs after treated with ExoHeLa. Inhibition of ER stress by knocking down protein kinase RNA-like endoplasmic reticulum kinase prevented the down-regulation of ZO-1 and Claudin-5 by ExoHeLa. Our study found that HeLa cell-derived exosomes promote metastasis by triggering ER stress in endothelial cells and break down endothelial integrity. Such effect of exosomes is microRNA-independent.