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The biochar (BC) pyrolyzed from corn straw (CS), spent mushroom substrate (SMS) and hardwood sawdust (HS), which are activated by K2CO3, were utilized for lead (Pb) and cadmium (Cd) sorption in solution. The effects of different pyrolysis factors on the Pb and Cd sorption capacities of three types of K2CO3-activated biochar (ABC) were analyzed. A series of characterization analyses were applied to compare the differences between various ABCs and to explore the Pb and Cd removal mechanisms. The results showed that the pyrolysis temperature, residence time and K2CO3 concentration obviously affect the sorption capacity of all ABCs. According to characterization, SMS had a loosely porous structure, which might be more favorable for K2CO3 activation. Furthermore, SMS possessed a rich elemental composition. Therefore, the pyrolysis product derived from SMS exhibited a larger specific surface area and higher polar functional group content, which might be the reason why ABCs synthesized from SMS exhibited better Pb and Cd sorption capacities than did ABCs synthesized from CS or HS. Moreover, the contributions of different Pb or Cd sorption mechanisms by different ABCs decreased as follows: mineral precipitation > cation exchange > complexation of oxygen-containing functional groups > π-bonding or physical sorption. Overall, the ABC synthesized from SMS was more suitable for Pb or Cd removal in solution, which also provided a new approach for the comprehensive utilization of SMS. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)–related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance. Editor's summary: Cancer-associated fibroblasts (CAFs) are stromal cells that make up most of the tumor microenvironment (TME) and have been implicated in cancer progression and relapse, including in breast cancer (BC). Here, Fan et al. have identified a subset of TSPAN8+ myofibroblastic CAFs (myCAFs) that correlated to chemoresistance and poor survival in patients with BC. They found that these myCAFs potentiated stemness of BC cells through down-regulation of SIRT6. They next treated xenograft mice with the SIRT6 activator MDL-800 and anti-TSPAN8 antibody, which increased sensitivity to chemotherapy, suggesting a potential target that requires further investigation. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore– elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC. Cuproptosis regulation in tumors is unclear. Here the authors find that copper promotes METTL16 lactylation, inducing cuproptosis via stabilizing FDX1 in gastric cancer. Targeting lactyl-METTL16 and cuproptosis offers a potential feasible strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

The pollution of lead (Pb (II)) to water resources is becoming more and more serious. It is always a difficult problem to find efficient and low‐cost adsorbents. Chicken manure (CM) and Chinese medicine residue (CMR) were modified with potassium dihydrogen phosphate (KH2PO4) and pyrolyzed to obtain a modified material (PBC) for the treatment of Pb(II) in an aqueous solution. A variety of characterization analysis results could prove that KH2PO4 was successfully introduced to PBC. By adjusting the initial pH, the zeta potential of PBC varies from −3.2 to −43.1 mV, it could be seen that PBC had excellent applicability in the broad range pH value (1.0–6.0). Experimental and model results showed that R2 of the pseudo‐first order kinetic model and the pseudo‐second order kinetic model are greater than 0.99, indicating that that physical and chemical adsorption played a significant role in Pb(II) removal by PBC. An adsorption isotherm analysis showed that the adsorption capacity n in this study is greater than 1, confirming that PBC has a good adsorption effect on Pb (II). R2 of the Langmuir model of PBC is 0.981, and its maximum adsorption capacity of Pb(II) could reach 599.4 mg/g. Environmentally friendly PBC could be used as an effective adsorbent to remove Pb(II) from aqueous systems. Research highlights: Chicken manure and Chinese medicine residue were converted into biochar to improve utilization.The modified biochar exhibited extraordinary Pb(II) adsorption capacity.Adsorption mechanisms: Surface complexation, ions exchange, coprecipitation, and so on.Remained great Pb(II) removal efficiency at different pH and Pb(II) concentration. [ABSTRACT FROM AUTHOR]

Municipal sewage sludge (MSS) and hazelnut shells were selected for co-pyrolysis and chemically activated with K2CO3 in a N2 atmosphere. The biochar was then modified by photocatalysis. Hazelnut shells, as a solid waste, were selected as a carbon source additive because of its high cellulose content and similar structure to natural wood. Using hazelnut shells could increase the specific surface area, enhance the porosity, and improve the adsorption capacity of the biochar. Hazelnut shells could also reduce the content of heavy metals in the raw biochar materials, along with increasing the ecological security of biochar and contributing to its further development and utilization. FTIR was used to study the changes in the functional groups on the biochar surface. The layered porous structure of the biochar was observed by SEM. The Cu(II) adsorption capacity of the biochar was 42.28 mg/g after 24 h. The Langmuir and pseudo-second-order models effectively described Cu(II) adsorption. [ABSTRACT FROM AUTHOR]

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2 K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Periodontitis is a chronic inflammatory disease characterized by plaque accumulation, resulting in immune microenvironment disorders and resorption of alveolar bone. To promote bone healing under inflammatory environments, a functional biomaterial based on disease pathophysiology is designed. A novel fatty acid C10-modified polypeptide, C 10 -KR8, is discovered to have excellent abilities in modulating macrophage repolarization and promoting bone regeneration in periodontitis. To build a multifunctional material localized drug delivery system, C 10 -KR8@ZIF-8 (C 10 -KR8-loaded zeolitic imidazolate framework-8) nanoparticles are constructed to sustainedly release the C 10 -KR8 peptide and Zn elements. By synergistic effects of providing a dynamic immuno-modulatory environment and promoting osteogenesis under pathological conditions, the obtained pH-responsive nanoparticles display excellent bone regeneration capability. Furthermore, coimmunoprecipitation/liquid chromatography-tandem mass spectrometry analysis and proteomics analysis revealed that the C 10 -KR8 peptide directly interacts with the high-temperature requirement protein A1 (Htra1), and C 10 -KR8@ZIF-8 nanoparticles promote the osteogenic differentiation of bone mesenchymal stem cells by activating the focal adhesion kinase (FAK)/phosphatidylinositide 3-kinase (PI3K)/AKT pathway and enhancing the nuclear localization of Yes-associated protein (YAP). Taken together, this study demonstrates C 10 -KR8 peptide regulate osteoimmunology and bone regeneration by Htra1/FAK/YAP pathway and that ZIF-8-based peptide loading platform is a promising strategy for periodontitis., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Xuechun Wang et al.)

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8) + myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8 + myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8 + myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser 772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1 , which caused TSPAN8 + myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8 + SIRT6 low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8 + myCAFs is a promising approach to circumvent chemoresistance.

Hypopharyngeal squamous cell carcinoma (HSCC) is a highly aggressive malignancy that constitutes approximately 95% of all hypopharyngeal carcinomas, and it carries a poor prognosis. The primary factor influencing the efficacy of anti-cancer drugs for this type of carcinoma is chemoresistance. Carnitine palmitoyltransferase 1A (CPT1A) has been associated with tumor progression in various cancers, including breast, gastric, lung, and prostate cancer. The inhibition or depletion of CPT1A can lead to apoptosis, curbing cancer cell proliferation and chemoresistance. However, the role of CPT1A in HSCC is not yet fully understood. In this study, we discovered that CPT1A is highly expressed in HSCC and is associated with an advanced T-stage and a poor 5-year survival rate among patients. Furthermore, the overexpression of CPT1A contributes to HSCC chemoresistance. Mechanistically, CPT1A can interact with the autophagy-related protein ATG16L1 and stimulate the succinylation of ATG16L1, which in turn drives autophagosome formation and autophagy. We also found that treatment with 3-methyladenine (3-MA) can reduce cisplatin resistance in HSCC cells that overexpress CPT1A. Our findings also showed that a CPT1A inhibitor significantly enhances cisplatin sensitivity both in vitro and in vivo. This study is the first to suggest that CPT1A has a regulatory role in autophagy and is linked to poor prognosis in HSCC patients. It presents novel insights into the roles of CPT1A in tumorigenesis and proposes that CPT1A could be a potential therapeutic target for HSCC treatment., Competing Interests: The authors declare no competing interests.

Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Cardiac fibrosis is a primary phenotype of cardiac remodeling that contributes to cardiac dysfunction and heart failure. The expansion and activation of CD4 + T cells in the heart has been identified to facilitate pathological cardiac remodeling and dysfunction; however, the underlying mechanisms remained not well clarified. Herein, we found that exosomes derived from activated CD4 + T cells (CD4-activated Exos) evoked pro-fibrotic effects of cardiac fibroblasts, and their delivery into the heart aggravated cardiac fibrosis and dysfunction post-infarction. Mechanistically, miR-142-3p that was enriched in CD4-activated Exos recapitulated the pro-fibrotic effects of CD4-activated Exos in cardiac fibroblasts, and vice versa. Furthermore, miR-142-3p directly targeted and inhibited the expression of Adenomatous Polyposis Coli (APC), a negative WNT signaling pathway regulator, contributing to the activation of WNT signaling pathway and cardiac fibroblast activation. Thus, CD4-activated Exos promote post-ischemic cardiac fibrosis through exosomal miR-142-3p-WNT signaling cascade-mediated activation of myofibroblasts. Targeting miR-142-3p in CD4-activated Exos may hold promise for treating cardiac remodeling post-MI.