S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma.

Background: S100A8, a calcium-binding protein belonging to the S100 family, is involved in immune responses and multiple tumor pathogens. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of B-cell lymphoma and remains incurable in 40% of patients. However, the role of S100A8 and its regulation of the immune response in DLBCL remain unclear. Methods: The differential expression of S100A8 was identified via the GEO and TCGA databases. The prognostic role of S100A8 in DLBCL was calculated using the Kaplan-Meier curve. The function enrichment of differentially expressed genes (DEGs) was explored through GO, KEGG, GSEA, and PPI analysis. In our cohort, the expression of S100A8 was verified. Meanwhile, the biological function of S100A8 was applied after the inhibition of S100A8 in an in vitro experiment. The association between S100A8 and immune cell infiltration and treatment response in DLBCL was analyzed. Results: S100A8 was significantly overexpressed and related to a poor prognosis in DLBCL patients. Function enrichment analysis revealed that DEGs were mainly enriched in the IL-17 signaling pathway. Our cohort also verified this point. In vitro experiments suggested that inhibition of S100A8 should promote cell apoptosis and suppress tumor growth. Single-cell RNA sequence analysis indicated that S100A8 might be associated with features of the tumor microenvironment (TME), and immune infiltration analyses discovered that S100A8 expression was involved in TME. In terms of drug screening, we predicted that many drugs were associated with preferable sensitivity. Conclusion: Elevated S100A8 expression is associated with a poor prognosis and immune infiltration in DLBCL. Inhibition of S100A8 could promote cell apoptosis and suppress tumor growth. Meanwhile, S100A8 has the potential to be a promising immunotherapeutic target for patients with DLBCL.

3D edible scaffolds with yeast protein: A novel alternative protein scaffold for the production of high-quality cell-cultured meat.

The purpose of this study was to develop a novel edible scaffold by utilizing yeast proteins, which could partially replace collagen and produce hypoallergenic, odorless, and highly nutritious cell-cultured meat that meets the demands of a more significant number of consumers. The scaffold comprised proanthocyanidins, dialdehyde chitosan, collagen, and different proportions of yeast proteins (YP). The results indicated that the scaffold possessed excellent mechanical properties and biocompatibility, and supported cell proliferation and myogenic differentiation. Additionally, we evaluated the texture characteristics of the cultured meat models and traditional beef and discovered that the YP30 cultured meat model had similar springiness and chewiness as beef. Subsequently, further analyzed the similarity between the cultured meat models and traditional beef in appearance, taste, and nutrition. Further results illustrated that the yeast protein cultured meat model exhibited a complete model structure and comparable color and taste to beef after frying. Moreover, it was concluded that the protein content of the YP30 cultured meat model was closer to that of beef. These findings suggested that the edible scaffold using yeast proteins has enormous potential to facilitate the sustainable development of the cell-cultured meat industry.

Production of green-natural and "authentic" cultured meat based on proanthocyanidins-dialdehyde chitosan-collagen ternary hybrid edible scaffolds.

Cultured meat has the potential to fulfill the meat demand for the growing human population, but cultured meat development will be required to simplify the production process and produce naturally cultured meat, such as no longer stripping off scaffolders and adding artificial dyes. In this study, proanthocyanidins (PC) and dialdehyde chitosan (DAC) were employed as dual crosslinkers with collagen to prepare a hybrid 3D edible scaffold for the production of high-quality cell-cultured meat. The results revealed that the scaffold was biocompatible and could offer robust mechanical support and adhesion sites for bovine myoblasts, enabling long-term cell culture. Meanwhile, the Col-PC-DAC scaffold promoted the myogenic differentiation of bovine myoblasts and extracellular matrix protein secretion, further affecting the texture of cultured meat. After cooking the cultured meat and beef, it was shown that the cultured meat had some similarities to beef in color and flavor. Importantly, our findings demonstrate that cultured meat can acquire a color remarkably similar to that of conventional beef without the need for artificial dyeing. This breakthrough not only simplifies the production process but also ensures a more natural and appealing appearance of cultured meat. In conclusion, the proanthocyanidins-dialdehyde chitosan-collagen hybrid 3D edible scaffolds provide a new option for producing cultured meat that satisfies consumer expectations.

Correction: A H2O2 self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy.

[This corrects the article DOI: 10.1039/C9SC05506A.].

Effects of proanthocyanidins and dialdehyde chitosan on the proliferation and differentiation of bovine myoblast for cultured meat production.

Cultured meat technology intends to manufacture meat by cultivating muscle stem cells in vitro, which is an emerging methodology in meat production. However, the insufficient stemness of bovine myoblasts cultivated in vitro declined the ability of cell expansion and myogenic differentiation, which limited the production of cultured meat. Therefore, in this study, we introduced proanthocyanidins (PC, natural polyphenolic compounds) and dialdehyde chitosan (DAC, natural polysaccharides) to explore the effects of proliferation and differentiation of bovine myoblasts in vitro. The experiment results revealed that PC and DAC promoted cell proliferation by improving the transition from G1 to the S phase as well as cell division in G2. Meanwhile, the myogenic differentiation of cells was further boosted by the combined PC and DAC up-regulation of MYH3 expression. Moreover, the study revealed the synergistic effect of PC and DAC on enhancing the structural stability of collagen, and bovine myoblasts demonstrated excellent growth and dispersion ability on collagen scaffolds. It is concluded that both PC and DAC promote the proliferation and differentiation of bovine myoblasts, contributing to the development of cultured meat production systems.

Long-term preservation at low temperature of Escherichia coli cells embedded in egg white glass formed by slow drying at room temperature.

Sterile homogeneous egg white (EW) is obtained through a three-step process, high-speed homogenization, centrifugation, and ultraviolet radiation. After incorporating 1.056 × 1010 CFU/g of Escherichia coli, the EW mixture was dehydrated by slow drying to form a brittle, water-soluble, and transparent bacteria-embedded egg white glass (BE-EWG). The BE-EWG stored at -20 °C for 4 months maintains almost all the cell growth functions and proliferation activities of the labeled E. coli, and most of the cell functions and 60 % of the proliferation activities are maintained for up to one year. The BE-EWG exhibits a porous hydrogel membrane structure after heat treatment, and many E. coli cells are accommodated in a grid with a pore size of 2-10 mm. The loss of bacteria-carrying viability after storage at room temperature may be related to the Maillard reaction between protein and glucose in EW, which results in the structural changes caused by protein cross-linking, darkened color and water insolubility of the BE-EWG. Therefore, the method of embedding E. coli cells in EWG as solid form at room temperature to avoid ice crystal formation during cryopreservation is more beneficial for storage, packaging and shipping at -20 °C.

Green immobilization and efficient proliferation of Escherichia coli cells in polyvinyl alcohol hydrogel membranes by unidirectional nanopore dehydration.

BACKGROUND: The immobilized technology for microbial or cells has the advantages of high microbial activity, high microbial density per unit space, good tolerance, strong shock, load resistance, high processing efficiency, and high reuse rate. It is now widely used in environmental remediation, water quality treatment, biodegradation, food industry, chemical analysis, energy development, medicine and pharmaceuticals, and other fields. RESULTS: A novel Escherichia coli cell-immobilizing polyvinyl alcohol hydrogel membrane (ECI-PVAHM) was prepared by unidirectional nanopore dehydration (UND) from a 10% polyvinyl alcohol (PVA) aqueous solution containing enhanced green fluorescent protein-labeled E. coli. This bacteria-loaded film has high water stability, flexibility, transparency, and mechanical robustness. Its tensile strength, elongation rate, and swelling rate are in the ranges 0.66-0.90 MPa, 300-390%, and 330-800%, respectively. The effective bacterial load of ECI-PVAHM is 2.375 × 109-1010 CFU/g (dry weight), which does not affect the original crystal structure of the PVAHM. This biofilm has a porous network structure with pore sizes between 0.2 and 1.0 µm, and these cells are embedded in the PVAHM network. When the immobilized cells were continuously cultured for 20 days, and the medium was renewed twice daily, their relative proliferation efficiency after 40 cycles could still be maintained at ~ 91%. CONCLUSION: The above results show that the cell division, proliferation ability, and metabolic activity of immobilized E. coli were not affected by the physical barrier of the porous network structure of the hydrogel. This UND-based ECI-PVAHM has potential applications in molecular biology, biopharmaceutical expression and production, bioreactors, and fuel cells.

γ-Fe2 O3 Loading Mitoxantrone and Glucose Oxidase for pH-Responsive Chemo/Chemodynamic/Photothermal Synergistic Cancer Therapy.

Traditional cancer therapy is limited by poor prognosis and risk of recurrence. Emerging therapies offer alternatives to these problems. In addition, synergistic therapy can combine the advantages of multiple therapies to eliminate cancer cells while attenuating damage to normal tissues. Herein, a theranostic nanoplatform based on the chemotherapeutic drug mitoxantrone (MTO) and glucose oxidase (GOx) co-loaded γ-Fe2 O3 nanoparticles (MTO-GOx@γ-Fe2 O3 NPs) is designed and prepared to realize photoacoustic imaging-guided chemo/chemodynamic/photothermal (CT/CDT/PTT) synergistic cancer therapy. With a particle size of about 86.2 nm, the synthesized MTO-GOx@γ-Fe2 O3 NPs can selectively accumulate at tumor sites by enhanced permeability and retention (EPR) effects. After entering cancer cells by endocytosis, MTO-GOx@γ-Fe2 O3 NPs decompose into Fe3+ ions and release cargo because of their pH-responsive characteristic. As a Food and Drug Administration (FDA)-approved chemotherapy drug, MTO shows strong DNA disruption ability and satisfying photothermal conversion ability under laser irradiation for photothermal therapy. Simultaneously, GOx catalyzes the decomposition of glucose and generates hydrogen peroxide (H2 O2 ) to enhance the chemodynamic therapy efficiency. In vitro and in vivo experiments reveal that MTO-GOx@γ-Fe2 O3 NPs possess a significant synergistic therapeutic effect in cancer treatment.

Efficacy and safety of alectinib in ALK-positive non-small cell lung cancer and blood markers for prognosis and efficacy: a retrospective cohort study.

Background: Alectinib is a second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs), which has attracted much attention in the treatment of ALK-positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed. This study assessed the efficacy of alectinib in patients with ALK-positive NSCLC and analyzed the prognostic factors. Methods: Patients with ALK-positive NSCLC who were confirmed by histopathology or cytology at the Affiliated Cancer Hospital of Nanjing Medical University between October 2018 and October 2021 were enrolled. All patients were treated with alectinib. The clinical characteristics and circulating tumor biomarkers before and after treatment were collected. Kaplan-Meier test was used to calculate the progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to explore the influencing factors on PFS. Incidence of adverse events was observed. Results: Twenty patients progressed after first-line treatment (n=59) with alectinib, and 21 patients progressed following second-line treatment (n=36) with alectinib. The median PFS of first-line treatment patients was not achieved, and the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23]. The most common adverse reactions were liver dysfunction (37.50%), anemia (37.50%), and constipation (20.83%). The incidence of grade III and above adverse reactions was 6.25%. Univariate analysis showed that neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR) =0.424, P=0.005] carcinoembryonic antigen (CEA; HR =0.482, P=0.029), lactate dehydrogenase (LDH; HR =0.327, P<0.001), carbohydrate antigen (CA)199 (HR =0.313, P=0.002), and circulating cell free DNA (cfDNA; HR =0.229, P=0.008) concentration levels were associated with PFS, and multivariate analysis showed that NLR (HR =3.058, P=0.034) was independent prognostic factor. After three months of treatment, CEA, CA199, NLR, and LDH, could further predict the prognosis of alectinib treatment. Conclusions: The efficacy and safety of alectinib as a first-line or second-line treatment for ALK-positive NSCLC in keeping with published prospective studies. CEA, CA199, NLR, and LDH within the normal range after three months of treatment were associated with good prognosis. Detection of serum tumor markers can indicate therapeutic success in patients treated with alectinib.

Degraded Sericin Significantly Regulates Blood Glucose Levels and Improves Impaired Liver Function in T2D Rats by Reducing Oxidative Stress.

Sericin could be degraded well into low-molecular-weight sericin (SS) through a novel and environmentally friendly recycling process using an ultrasonically degumming method in Ca(OH)2 aqueous solution. The oral administration of the SS has an evidently hypoglycemic effect on STZ-induced T2D rats. At oral doses of 2.5 and 5% SS for four weeks, the fasting blood glucose decreased by over 60% compared with that in the untreated model group. Oral glucose tolerance and insulin tolerance were ameliorated by the peptide treatment. The serum insulin level was reduced by approximately 35%, the insulin resistance index was reduced by more than 66%. The 8-hydroxy-2 deoxyguanosine level showed a large reduction of 20%, and the total antioxidant activities significantly increased. Hematoxylin-eosin staining and fluorescent immunostaining sections showed that liver and pancreas damage was partly recovered in T2D rats. In summary, oral SS demonstrated evidently hypoglycemic effects mainly related to reducing oxidative stress in the damaged liver and pancreas of T2D rats. Therefore, these results have suggested that the degraded sericin has a potential use in SS-based healthy functional food or hypoglycemic drugs as a waste recovered from sericulture resources.

Mitoxantrone as photothermal agents for ultrasound/fluorescence imaging-guided chemo-phototherapy enhanced by intratumoral H2O2-Induced CO.

Multimodal imaging integrated theranostic nanomaterials provides broad prospects for noninvasive and precise cancer treatment. However, the uncertain physiological metabolism of the existing phototherapy nanoagents greatly prevents its clinical application. Herein, a smart nanoplatform based on clinically chemotherapeutic drugs mitoxantrone (MTO) was prepared to realize ultrasound/fluorescence imaging-guided chemo-photothermal combined therapy. The nanoplatform encapsulating MTO and manganese carbonyl (MnCO), which denoted as MCMA NPs, could accumulate at tumor sites by enhanced permeability and retention (EPR) effect and effectively induce cell apoptosis. MTO with near-infrared absorption (~676 nm) not only acted as chemotherapy drug, but also served as photothermal reagent with high photothermal conversion efficiency (ƞ = 42.2%). Especially, H2O2 in tumor sites and the photothermal effect of MTO could trigger MnCO to generate CO, which made cancer cells more sensitive to MTO and significantly alleviated cell resistance. Simultaneously, CO released in tumor also could act as contrast agent for tumor ultrasound imaging to provide accurate guidance for anticancer treatment. Moreover, MCMA NPs could further promote oxidative stress damage in mitochondria and protect normal cells from side effects of chemotherapy. Both in vivo and in vitro studies indicated that MCMA NPs possessed excellent synergetic tumor inhibition ability with high efficiency and low chemotherapy resistance.

Aza-BODIPY-Based Nanomedicines in Cancer Phototheranostics.

Cancer phototheranostics, composed of optical diagnosis and phototherapy (including photodynamic therapy and photothermal therapy), is a promising strategy for precise tumor treatment. Due to the unique properties of near-infrared absorption/emission, high reactive oxygen species generation, and photothermal conversion efficiency, aza-boron-dipyrromethene (aza-BODIPY), as an emerging organic photosensitizer, has shown great potential for tumor phototheranostics. By encapsulating aza-BODIPY photosensitizers within functional amphiphilic polymers, we can afford hydrophilic nanomedicines that selectively target tumor sites via an enhanced permeability and retention effect, thereby efficiently improving diagnosis and therapeutic efficacy. Herein, in this spotlight article, we attempt to highlight our recent contributions in the development of aza-BODIPY-based nanomedicines, which comprises three main sections: (1) to elucidate the design strategy of aza-BODIPY photosensitizers and corresponding nanomedicines; (2) to overview their photophysical properties and biomedical applications in phototheranostics, including fluorescence imaging, photoacoustic imaging, photodynamic therapy, photothermal therapy, and synergistic therapy; and (3) to depict the challenges and future perspectives of aza-BODIPY nanomedicines. It is believed that this Spotlight on Applications article would illuminate the way of developing new aza-BODIPY nanomedicines as well as other organic photosensitizer-based nanomedicines for future clinical translation.

A H2O2 self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (˙OH) to kill cancer cells, holds high promise in tumor therapy due to its high selectivity. However, the anticancer efficacy is unsatisfactory owing to the limited concentration of endogenous H2O2. Herein, thermal responsive nanoparticles with H2O2 self-sufficiency are fabricated by utilizing organic phase change materials (PCMs) to encapsulate iron-gallic acid nanoparticles (Fe-GA) and ultra-small CaO2. PCMs, acting as the gatekeeper, could be melted down by the hyperthermia effect of Fe-GA under laser irradiation with a burst release of Fe-GA and CaO2. The acidic tumor microenvironment would further trigger CaO2 to generate a large amount of H2O2 and Ca2+. The self-supplied H2O2 would be converted into ˙OH by participating in the Fenton reaction with Fe-GA. Meanwhile, in situ generation of Ca2+ could cause mitochondrial damage and lead to apoptosis of tumor cells. With efficient tumor accumulation illustrated in in vivo photoacoustic imaging, Fe-GA/CaO2@PCM demonstrated a superior in vivo tumor-suppressive effect without inducing systemic toxicity. The study presents a unique domino effect approach of PCM based nanoparticles with thermal responsiveness, H2O2 self-supply, and greatly enhanced CDT effects, showing bright prospects for highly efficient tumor treatment.

On-surface isostructural transformation from a hydrogen-bonded network to a coordination network for tuning the pore size and guest recognition.

Rational manipulation of supramolecular structures on surfaces is of great importance and challenging. We show that imidazole-based hydrogen-bonded networks on a metal surface can transform into an isostructural coordination network for facile tuning of the pore size and guest recognition behaviours. Deposition of triangular-shaped benzotrisimidazole (H3btim) molecules on Au(111)/Ag(111) surfaces gives honeycomb networks linked by double N-H⋯N hydrogen bonds. While the H3btim hydrogen-bonded networks on Au(111) evaporate above 453 K, those on Ag(111) transform into isostructural [Ag3(btim)] coordination networks based on double N-Ag-N bonds at 423 K, by virtue of the unconventional metal-acid replacement reaction (Ag reduces H+). The transformation expands the pore diameter of the honeycomb networks from 3.8 Å to 6.9 Å, giving remarkably different host-guest recognition behaviours for fullerene and ferrocene molecules based on the size compatibility mechanism.

Fast inflows as the adjacent fuel of supermassive black hole accretion disks in quasars.

Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.

"Three-in-One" SERS Adhesive Tape for Rapid Sampling, Release, and Detection of Wound Infectious Pathogens.

The traditional colony culture method for detection of pathogens is subjected to the laborious and tedious experimental procedure, which limits its application in point-of-care (POC) testing and quick diagnosis. This work designs an intelligent adhesive tape as a "three-in-one" platform for rapid sampling, photocontrolled release, and surface-enhanced Raman scattering (SERS) detection of pathogens from infected wounds. This tape is constructed by encapsulating densely packed gold nanostars as SERS substrates between two pieces of graphene and modified with a synthetic o-nitrobenzyl derivative molecule to form an artificial biointerface for highly efficient pathogen capture via electrostatic interaction. The captured targets can be conveniently released onto a solid culture medium by UV cleavage of o-nitrobenzyl moiety for pathogen growth and in situ SERS detection. As a proof of strategy, this "three-in-one" platform has been used for detecting the concurrent infection of Pseudomonas aeruginosa and Staphylococcus aureus by pasting the tape on a skin burn wound. The impressive detection performance with an analytical time of only several hours for these pathogens at an early growth stage demonstrates its great potential as a POC testing device for health care.