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Wet-tissue adhesives have long been attractive materials for realizing complicated biomedical functions. However, the hydration film on wet tissues can generate a boundary, forming hydrogen bonds with the adhesives that weaken adhesive strength. Introducing black phosphorus (BP) is believed to enhance the water absorption capacity of tape-type adhesives and effectively eliminate hydration layers between the tissue and adhesive. This study reports a composite patch integrated with BP nanosheets (CPB) for wet-tissue adhesion. The patch’s improved water absorption and mechanical properties ensure its immediate and robust adhesion to wet tissues. Various bioapplications of CPB are demonstrated, such as rapid hemostasis (within ~1-2 seconds), monitoring of physical-activity and prevention of tumour-recurrence, all validated via in vivo studies. Given the good practicability, histocompatibility and biodegradability of CPB, the proposed patches hold significant promise for a wide range of biomedical applications. The utility of wet-tissue adhesives has been impeded by the suboptimal adhesive strength. Here the authors report a composite patch integrated with BP nanosheets that improve the wet-tissue adhesion by enhancing the water absorption and mechanical properties of the patch and demonstrate the uses of the patch in hemostasis, physical-activity monitoring and tumour-recurrence prevention.

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction. Sleep plays an important role in learning and memory. Here the authors show that experience dependent elimination of spines is attenuated by REM sleep deprivation.

Background Interactions between tumor and microenvironment determine individual response to immunotherapy. Triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) have exhibited suboptimal responses to immune checkpoint inhibitors (ICIs). Aspartate β-hydroxylase (ASPH), an oncofetal protein and tumor associated antigen (TAA), is a potential target for immunotherapy. Methods Subcutaneous HCC and orthotopic TNBC murine models were established in immunocompetent BALB/c mice with injection of BNL-T3 and 4 T1 cells, respectively. Immunohistochemistry, immunofluorescence, H&E, flow cytometry, ELISA and in vitro cytotoxicity assays were performed. Results The ASPH-MYC signaling cascade upregulates PD-L1 expression on breast and liver tumor cells. A bio-nanoparticle based λ phage vaccine targeting ASPH was administrated to mice harboring syngeneic HCC or TNBC tumors, either alone or in combination with PD-1 blockade. In control, autocrine chemokine ligand 13 (CXCL13)-C-X-C chemokine receptor type 5 (CXCR5) axis promoted tumor development and progression in HCC and TNBC. Interactions between PD-L1 + cancer cells and PD-1 + T cells resulted in T cell exhaustion and apoptosis, causing immune evasion of cancer cells. In contrast, combination therapy (Vaccine+PD-1 inhibitor) significantly suppressed primary hepatic or mammary tumor growth (with distant pulmonary metastases in TNBC). Adaptive immune responses were attributed to expansion of activated CD4 + T helper type 1 (Th1)/CD8 + cytotoxic T cells (CTLs) that displayed enhanced effector functions, and maturation of plasma cells that secreted high titers of ASPH-specific antibody. Combination therapy significantly reduced tumor infiltration of immunosuppressive CD4 + /CD25 + /FOXP3 + Tregs. When the PD-1/PD-L1 signal was inhibited, CXCL13 produced by ASPH + cancer cells recruited CXCR5 + /CD8 + T lymphocytes to tertiary lymphoid structures (TLSs), comprising effector and memory CTLs, T follicular helper cells, B cell germinal center, and follicular dendritic cells. TLSs facilitate activation and maturation of DCs and actively recruit immune subsets to tumor microenvironment. These CTLs secreted CXCL13 to recruit more CXCR5 + immune cells and to lyse CXCR5 + cancer cells. Upon combination treatment, formation of TLSs predicts sensitivity to ICI blockade. Combination therapy substantially prolonged overall survival of mice with HCC or TNBC. Conclusions Synergistic antitumor efficacy attributable to a λ phage vaccine specifically targeting ASPH, an ideal TAA, combined with ICIs, inhibits tumor growth and progression of TNBC and HCC.

It is well established that visual deprivation has a profound impact on the responsiveness of neurons in the developing visual cortex. The effect of visual deprivation on synaptic connectivity remains unclear. Using transcranial two-photon microscopy, we examined the effect of visual deprivation and subsequent recovery on dendritic spine remodeling of layer 5 pyramidal neurons in the mouse primary visual cortex. We found that monocular deprivation (MD), but not binocular deprivation (BD), increased dendritic spine elimination over 3 days in the binocular region of 4-week-old adolescent mice. This MD-induced dendritic spine elimination persisted during subsequent 2–4 days of binocular recovery. Furthermore, we found that average dendritic spine sizes were decreased and increased following 3-day MD and BD, respectively. These spine size changes induced by MD or BD tended to be reversed during subsequent binocular recovery. Taken together, these findings reveal differential effects of MD and BD on synaptic connectivity of layer 5 pyramidal neurons and underscore the persistent impact of MD on synapse loss in the developing visual cortex.

The coronavirus nucleocapsid (N) protein interacts with non-structural protein 3 (Nsp3) to facilitate viral RNA synthesis and stabilization. However, structural information on the N-Nsp3 complex is limited. Here, we report a 2.6 Å crystal structure of the N-terminal domain (NTD) of the N protein in complex with the ubiquitin-like domain 1 (Ubl1) of Nsp3 in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One NTD and two Ubl1s formed a stable heterotrimer. We performed mutational analysis to reveal the key residues for this interaction. We confirmed the colocalization of SARS-CoV-2 N and Nsp3 in Huh-7 cells. N-Ubl1 interaction also exists in SARS-CoV and Middle East respiratory syndrome coronavirus. We found that SARS-CoV-2 Ubl1 competes with RNA to bind N protein in a dose-dependent manner. Based on our results, we propose a model for viral ribonucleoprotein dissociation through N protein binding to Ubl1 of Nsp3. Reporting the crystal structure of the N-terminal domain of the viral nucleocapsid protein in complex with the ubiquitin-like domain 1 of Nsp3 in SARS-CoV-2

Background/Aim To investigate the prognostic value of circulating apolipoprotein AI (apoAI) levels and develop a new prognostic model in individuals with acute-on-chronic liver failure (ACLF) and acute decompensation (AD) of liver cirrhosis caused by hepatitis B virus (HBV) infection. Methods Baseline levels of serum lipids were measured, and data concerning the presence of complications were collected from 561 HBV-ACLF and AD patients. Survival analysis was conducted by log-rank test. Proportional hazards model was used to perform multivariate analysis. The dynamics of serum apoAI levels were also explored in 37 HBV-ACLF patients. Results In the cohort, the negatively correlation was found between the Model for End-Stage Liver Disease (MELD) score and serum apoAI levels ( r = -0.7946, P  < 0.001). Circulating apoAI concentration was an independent risk factor for 90-day survival according to Cox multivariate analysis. A new prognostic score-integrated serum lipid profile for ACLF patients (Lip-ACLF score = 0.86×International Normalized Ratio (INR) + 0.0034×total bilirubin (TBIL) (µmol/L) + 0.99× hepatorenal syndrome (HRS) (HRS: no/1; with/2) + 0.50×hepatic encephalopathy (HE) (grade/ponint: no/1; 1–2/2; 3–4/3) − 2.97×apoAI (g/L) + 5.2) was subsequently designed for the derivation cohort. Compared to MELD score, Child-Turcotte-Pugh (CTP) score or apoAI, Lip-ACLFs was superior for the prediction of 90-day outcomes (receiver operating characteristic curve (ROC): 0.930 vs. 0.885, 0.833 or 0.856, all P  < 0.01), as was the validation cohort (ROC 0.906 vs. 0.839, 0.857 or 0.837, all P  < 0.05). In Kaplan‒Meier survival analysis, low apoAI levels (< 0.42 g/L) at baseline indicated poor prognosis in ACLF and AD patients. Among the 37 patients, the deceased individuals were characterised with significantly decreased serum apoAI levels during the follow-up test compared with those at baseline ( P  < 0.05), whereas in patients with a good prognosis, the serum apoAI levels remained stable during the follow-up. Conclusion In HBV-ACLF and AD patients, lower serum apoAI levels suggest greater disease severity and 90-day mortality risk. For predicting the short-term prognosis of these patients, the new Lip-ACLF score might serve as a potential model.

Owing to the limitations of conventional cancer therapies, including chemotherapy, radiotherapy, and surgery, gene therapy has become a prominent strategy for cancer treatment over the past few decades. Gene therapy is a medical approach for targeting and destroying cancer cells by delivering exogenous genes into the target cancerous cells or surrounding tissues. However, successful delivery of foreign genes into target cells and tissues remains a key issue in such therapy. Efficient gene delivery systems would undoubtedly be important for improving the medical outcomes of gene therapy. With genetic modifications, viral vectors can target specific cells with high gene transduction efficiency, thus, the use of viral vectors is a promising technology for improving foreign gene delivery. Currently, four viral vectors—adenovirus, adeno‐associated virus, herpes simplex virus, and retrovirus—are dominantly being investigated and used in preclinical and clinical trials. In this review, we provide an overview of the mechanisms and latest applications of the four above‐mentioned viral vectors, and summarize the current development of several other viral vectors. In addition, we discuss the challenges and provide insights into future development of viral vectors in cancer treatment. Adenovirus, adeno‐associated virus, herpes simplex virus, and retrovirus have been utilized for cancer treatment. Ex vivo treatment: cells isolated from the patients are genetically modified by viral vectors and then transfused back into patients. In vivo treatment: viral vectors display the antitumor effects through expression of transgenes, particularly, oncolytic vectors can replicate in the tumor cells to lyse them.

A low-cost, highly efficient and eco-friendly cellulose-based adsorbent (CMGT) was synthesized and used to uptake Pb(II) and malachite green (MG) from aqueous solutions. The CMGT was characterized by FTIR, SEM, TGA and XRD. Different experimental parameters were evaluated in batch adsorption experiments to determine the optimal adsorption conditions. The optimal pHs for Pb(II) and MG were 5.5 and 7.0, respectively; the optimal contact times for Pb(II) and MG were 60 and 180 min, respectively. Among the Langmuir, Freundlich and Temkin isotherm models, the Langmuir model fitted the adsorption data best for both Pb(II) and MG adsorption. In theory, the maximum adsorption capacities of Pb(II) and MG were 584.80 and 131.93 mg g⁻¹, respectively. The pseudo-second-order model fitted the experimental data very well, and the thermodynamics were also used to discuss the mechanism in depth. Additionally, desorption tests showed that CMGT could be effectively regenerated by 0.2 mol L⁻¹ HCl solution and could be reused for at least six cycles successively with a stable sorption ability in the dynamic adsorption process.

Background Alzheimer’s disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. Methods We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice. We also performed calcium imaging to determine the effect of Aβ oligomers on dendritic calcium activity. In addition, structural and functional two-photon imaging were used to examine the link between abnormal dendritic calcium activity and changes in dendritic spine size in the AD mouse model. Results We found that somatic calcium activities of layer 2/3 neurons were significantly lower in the primary motor cortex of 3-month-old APPswe/PS1dE9 mice than in wild type mice during quiet resting, but not during running on a treadmill. Notably, a significantly larger fraction of apical dendrites of layer 2/3 pyramidal neurons showed calcium transients with abnormally long duration and high peak amplitudes during treadmill running in AD mice. Administration of Aβ oligomers into the brain of wild type mice also induced abnormal dendritic calcium transients during running. Furthermore, we found that the activity and size of dendritic spines were significantly reduced on dendritic branches with abnormally prolonged dendritic calcium transients in AD mice. Conclusion Our findings show that abnormal dendritic calcium transients and synaptic depotentiation occur before amyloid plaque formation in the motor cortex of the APPswe/PS1dE9 mouse model of AD. Dendritic calcium transients with abnormally long durations and high amplitudes could be induced by soluble Aβ oligomers and contribute to synaptic deficits in the early pathogenesis of AD.

Metal halides with efficient, stable, and tunable white light emission are ideal for lighting applications, because their emission properties can be effectively optimized through rational doping and precise compositional engineering. However, the synthesis of such materials often requires strict conditions and complex procedures. In this work, we report a phase transition from Sb-doped Cs2InCl5·H2O to Cs2NaInCl6, along with tunable white light emission. Partial substitution of Na+ enables the formation of high-energy multiple emission centers, resulting in efficient white light with an adjustable correlated color temperature ranging from 2500 K to 5000 K under 365 nm excitation. The photoluminescence quantum yield reaches up to 45.24%. Efficient energy transfer among emission centers and the doping concentration of Na+ are critical for achieving high-performance tunable white light. The synthesized Cs2NaxInCl5+x:Sb composite exhibits excellent stability under ultraviolet irradiation and environmental conditions such as oxygen and humidity, even after 200 h of ultraviolet irradiation, the emission spectrum remains stable, with more than 80% of its initial efficiency being preserved. Our results show its potential for advanced lighting applications and provide valuable insight for a desirable emission-tunable metal halide design.