Nitrite-driven anaerobic ethane oxidation.

Ethane, the second most abundant gaseous hydrocarbon in vast anoxic environments, is an overlooked greenhouse gas. Microbial anaerobic oxidation of ethane can be driven by available electron acceptors such as sulfate and nitrate. However, despite nitrite being a more thermodynamically feasible electron acceptor than sulfate or nitrate, little is known about nitrite-driven anaerobic ethane oxidation. In this study, a microbial culture capable of nitrite-driven anaerobic ethane oxidation was enriched through the long-term operation of a nitrite-and-ethane-fed bioreactor. During continuous operation, the nitrite removal rate and the theoretical ethane oxidation rate remained stable at approximately 25.0 mg NO2 -N L-1 d-1 and 11.48 mg C2H6 L-1 d-1, respectively. Batch tests demonstrated that ethane is essential for nitrite removal in this microbial culture. Metabolic function analysis revealed that a species affiliated with a novel genus within the family Rhodocyclaceae, designated as 'Candidatus Alkanivoras nitrosoreducens', may perform the nitrite-driven anaerobic ethane oxidation. In the proposed metabolic model, despite the absence of known genes for ethane conversion to ethyl-succinate and succinate-CoA ligase, 'Ca. A. nitrosoreducens' encodes a prospective fumarate addition pathway for anaerobic ethane oxidation and a complete denitrification pathway for nitrite reduction to nitrogen. These findings advance our understanding of nitrite-driven anaerobic ethane oxidation, highlighting the previously overlooked impact of anaerobic ethane oxidation in natural ecosystems.

BRD7 as key factor in PBAF complex assembly and CD8+ T cell differentiation.

Upon infection, naive CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this process have been demonstrated, the regulatory role of chromatin remodeling system in this process remains largely unknown. Here we show that BRD7, a component of the polybromo-associated BAF complex (PBAF), was required for naive CD8+ T cells to differentiate into functional short-lived effector cells (SLECs) in response to acute infections caused by influenza virus or lymphocytic choriomeningitis virus (LCMV). BRD7 deficiency in CD8+ T cells resulted in profound defects in effector population and functions, thereby impairing viral clearance and host recovery. Further mechanical studies indicate that the expression of BRD7 significantly turned to high from naive CD8+ T cells to effector cells, which bridged BRG1 and PBRM1 to the core module of PBAF complex, consequently facilitating the assembly of PBAF complex rather than BAF complex in the effector cells. The PBAF complex changed the chromatin accessibility at the loci of Tbx21 gene and upregulated its expression, leading to the maturation of effector T cells. Our research demonstrates that BRD7 and the PBAF complex are key in CD8+ T cell development and present a significant target for advancing immune therapies.

ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency.

The human immunodeficiency virus type 1 (HIV-1) reservoir consists of latently infected cells which present a major obstacle to achieving a functional cure for HIV-1. The formation and maintenance of HIV-1 latency have been extensively studied, and latency-reversing agents (LRAs) that can reactivate latent HIV-1 by targeting the involved host factors are developed; however, their clinical efficacies remain unsatisfactory. Therefore, it is imperative to identify novel targets for more potential candidates or better combinations for LRAs. In this study, we utilized CRISPR affinity purification in situ of regulatory elements system to screen for host factors associated with the HIV-1 long terminal repeat region that could potentially be involved in HIV-1 latency. We successfully identified that origin recognition complex 1 (ORC1), the largest subunit of the origin recognition complex, contributes to HIV-1 latency in addition to its function in DNA replication initiation. Notably, ORC1 is enriched on the HIV-1 promoter and recruits a series of repressive epigenetic elements, including DNMT1 and HDAC1/2, and histone modifiers, such as H3K9me3 and H3K27me3, thereby facilitating the establishment and maintenance of HIV-1 latency. Moreover, the reactivation of latent HIV-1 through ORC1 depletion has been confirmed across various latency cell models and primary CD4+ T cells from people living with HIV-1. Additionally, we comprehensively validated the properties of liquid-liquid phase separation (LLPS) of ORC1 from multiple perspectives and identified the key regions that promote the formation of LLPS. This property is important for the recruitment of ORC1 to the HIV-1 promoter. Collectively, these findings highlight ORC1 as a potential novel target implicated in HIV-1 latency and position it as a promising candidate for the development of novel LRAs. IMPORTANCE: Identifying host factors involved in maintaining human immunodeficiency virus type 1 (HIV-1) latency and understanding their mechanisms prepares the groundwork to discover novel targets for HIV-1 latent infection and provides further options for the selection of latency-reversing agents in the "shock" strategy. In this study, we identified a novel role of the DNA replication factor origin recognition complex 1 (ORC1) in maintaining repressive chromatin structures surrounding the HIV-1 promoter region, thereby contributing to HIV-1 latency. This discovery expands our understanding of the non-replicative functions of the ORC complex and provides a potential therapeutic strategy for HIV-1 cure.

Development of a PCSK9-targeted nanoparticle vaccine to effectively decrease the hypercholesterolemia.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) and mediates its internalization and degradation, resulting in an increase in LDL cholesterol levels. Recently, PCSK9 emerged as a therapeutic target for hypercholesterolemia and atherosclerosis. In this study, we develop a PCSK9 nanoparticle (NP) vaccine by covalently conjugating the catalytic domain (aa 153-aa 454, D374Y) of PCSK9 to self-assembled 24-mer ferritin NPs. We demonstrate that the PCSK9 NP vaccine effectively induces interfering antibodies against PCSK9 and reduces serum lipids levels in both a high-fat diet-induced hypercholesterolemia model and an adeno-associated virus-hPCSK9D374Y-induced hypercholesterolemia model. Additionally, the vaccine significantly reduces plaque lesion areas in the aorta and macrophages infiltration in an atherosclerosis mouse model. Furthermore, we discover that the vaccine's efficacy relied on T follicular help cells and LDLR. Overall, these findings suggest that the PCSK9 NP vaccine holds promise as an effective treatment for hypercholesterolemia and atherosclerosis.

Regulatory Mechanisms of Quorum Sensing System of Bacteria in Response to Chlorine and Ozone Disinfection.

Waterborne pathogens invariably present considerable threats to public health. The quorum sensing (QS) system is instrumental in coordinating bacterial growth and metabolisms. However, the responses and regulatory mechanisms of bacteria to various disinfection technologies through quorum sensing are still unclear. This study examines the inactivation effect of chlorination and ozonation on biofilms and planktonic cells of QS signaling-deficient mutants of Pseudomonas aeruginosa. Cell counting and viability assessment revealed that the combined disinfection of chlorine and ozone was the most effective for inactivating planktonic P. aeruginosa within 10 min of exposure. Additionally, microfluidic chip culture demonstrated that the secretion of quinolone signals escalated biofilms' disinfection resistance. Disinfection exposure significantly altered the gene expression of wild-type strains and QS signaling-deficient mutants. Moreover, the QS system triggered multilayered gene expression programs as a responsive protection to disinfectant exposure, including oxidative stress, ribosome synthesis, and the nutrient absorption of bacteria. These insights broaden our understanding of bacterial QS in response to disinfection, promising potential strategies toward efficient disinfection processes.

Synergistic degradation of Tris (2-Chloroethyl) Phosphate (TCEP) by US/Fenton system: Experimental, DFT calculation and toxicity evaluation.

Organophosphorus esters (OPEs), exemplified by tris (2-chloroethyl) phosphate (TCEP), find extensive application in diverse industries such as construction materials, textiles, chemical manufacturing, and electronics, consequently resulting in an increased concentration of these compounds in industrial wastewater. The fundamental objective of this investigation was to examine the degradation of TCEP through the implementation of US/Fenton oxidation techniques in a solution. The findings revealed that the US/Fenton system effectively facilitated the degradation of TCEP, with the Chan kinetic model precisely elucidating the degradation process. Under optimized reaction conditions, the degradation efficiency of TCEP reached an impressive 93.18%. However, the presence of common co-existing aqueous substrates such as Cl-, HCO3-, H2PO4-, and HA hindered the degradation process. Bursting tests and electron paramagnetic resonance (EPR) studies affirmed ∙OH oxidation as the principal mechanism underlying TCEP degradation. Detailed degradation pathways for TCEP were established through the utilization of density-functional theory (DFT) calculations and GC/MS tests. Moreover, the ecotoxicological evaluation of TCEP and its intermediates was conducted using the Toxicity Estimation Software Tool (T.E.S.T.).

Deciphering the formation of granules by n-DAMO and Anammox microorganisms.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process is a promising wastewater treatment technology, but the slow microbial growth rate greatly hinders its practical application. Although high-level nitrogen removal and excellent biomass accumulation have been achieved in n-DAMO granule process, the formation mechanism of n-DAMO granules remains unresolved. To elucidate the role of functional microbes in granulation, this study attempted to cultivate granules dominated by n-DAMO microorganisms and granules coupling n-DAMO with anaerobic ammonium oxidation (Anammox). After long-term operation, dense granules were developed in the two systems where both n-DAMO archaea and n-DAMO bacteria were enriched, whereas granulation did not occur in the other system dominated by n-DAMO bacteria. Extracellular polymeric substances (EPS) measurement indicated the critical role of EPS production in the granulation of n-DAMO process. Metagenomic and metatranscriptomic analyses revealed that n-DAMO archaea and Anammox bacteria were active in EPS biosynthesis, while n-DAMO bacteria were inactive. Consequently, more EPS were produced in the systems containing n-DAMO archaea and Anammox bacteria, leading to the successful development of n-DAMO granules. Furthermore, EPS biosynthesis in n-DAMO systems is potentially regulated by acyl-homoserine lactones and c-di-GMP. These findings not only provide new insights into the mechanism of granule formation in n-DAMO systems, but also hint at potential strategies for management of the granule-based n-DAMO process.

Deciphering the reduction of antibiotic resistance genes (ARGs) during medium-chain fatty acids production from waste activated sludge: Driven by inhibition of ARGs transmission and shift of microbial community.

Medium-chain fatty acids (MCFAs) production from waste activated sludge (WAS) by chain extension (CE) is a promising technology. However, the effects and mechanisms of CE process on the fate of antibiotic resistance genes (ARGs) remain unclear. In this study, the results showed that the removal efficiency of ARGs was 81.15 % in CE process, suggesting its efficacy in reducing environmental risks. Further, the observed decrease in mobile genetic elements (MGEs) indicated that CE process restricted the horizontal gene transfer (HGT). Complementing this, the increase in soluble organic matters and extracellular 16 S rDNA confirmed that MCFAs production caused bacterial damage. Decreased intracellular ARGs and increased extracellular ARGs further revealed that MCFAs production impaired ARGs hosts, thereby limiting the vertical gene transfer (VGT) of ARGs. Shift of microbial community combined with co-occurrence network analysis demonstrated that functional bacteria without host potential for ARGs were enriched, but potential ARGs and MGEs hosts decreased, showing the role of functional bacterial phylogeny and selection pressure of MCFAs in reducing ARGs. Finally, partial least squares path model was used to systematic verify the mechanism of ARGs removal in CE process, which was attributed to the inhibition of ARGs transmission (HGT and VGT) and shift of microbial community.

Anaerobic ammonium oxidation coupled with sulfate reduction links nitrogen with sulfur cycle.

Sulfate-dependent ammonium oxidation (Sulfammox) is a critical process linking nitrogen and sulfur cycles. However, the metabolic pathway of microbes driven Sulfammox is still in suspense. The study demonstrated that ammonium was not consumed with sulfate as the sole electron acceptor during long-term enrichment, probably due to inhibition from sulfide accumulation, while ammonium was removed at âˆ¼ 10 mg N/L/d with sulfate and nitrate as electron acceptors. Ammonium and sulfate were converted into nitrogen gas, sulfide, and elemental sulfur. Sulfammox was mainly performed by Candidatus Brocadia sapporoensis and Candidatus Brocadia fulgida, both of which encoded ammonium oxidation pathway and dissimilatory sulfate reduction pathway. Not sulfide-driven autotrophic denitrifiers but Candidatus Kuenenia stuttgartiensis converted nitrate to nitrite with sulfide. The results of this study reveal the specialized metabolism of Sulfammox bacteria (Candidatus Brocadia sapporoensis and Candidatus Brocadia fulgida) and provide insight into microbial relationships during the nitrogen and sulfur cycles.

Biochar-based composites for removing chlorinated organic pollutants: Applications, mechanisms, and perspectives.

Chlorinated organic pollutants constitute a significant category of persistent organic pollutants due to their widespread presence in the environment, which is primarily attributed to the expansion of agricultural and industrial activities. These pollutants are characterized by their persistence, potent toxicity, and capability for long-range dispersion, emphasizing the importance of their eradication to mitigate environmental pollution. While conventional methods for removing chlorinated organic pollutants encompass advanced oxidation, catalytic oxidation, and bioremediation, the utilization of biochar has emerged as a prominent green and efficacious method in recent years. Here we review biochar's role in remediating typical chlorinated organics, including polychlorinated biphenyls (PCBs), triclosan (TCS), trichloroethene (TCE), tetrachloroethylene (PCE), organochlorine pesticides (OCPs), and chlorobenzenes (CBs). We focus on the impact of biochar material properties on the adsorption mechanisms of chlorinated organics. This review highlights the use of biochar as a sustainable and eco-friendly method for removing chlorinated organic pollutants, especially when combined with biological or chemical strategies. Biochar facilitates electron transfer efficiency between microorganisms, promoting the growth of dechlorinating bacteria and mitigating the toxicity of chlorinated organics through adsorption. Furthermore, biochar can activate processes such as advanced oxidation or nano zero-valent iron, generating free radicals to decompose chlorinated organic compounds. We observe a broader application of biochar and bioprocesses for treating chlorinated organic pollutants in soil, reducing environmental impacts. Conversely, for water-based pollutants, integrating biochar with chemical methods proved more effective, leading to superior purification results. This review contributes to the theoretical and practical application of biochar for removing environmental chlorinated organic pollutants.

Nitrate-dependent anaerobic methane oxidation coupled to Fe(III) reduction as a source of ammonium and nitrous oxide.

'Candidatus Methanoperedens nitroreducens' is an archaeal methanotroph with global importance that links carbon and nitrogen cycles and great potential for sustainable operation of wastewater treatment. It has been reported to mediate the anaerobic oxidation of methane through a reverse methanogenesis pathway while reducing nitrate to nitrite. Here, we demonstrate that 'Ca. M. nitroreducens' reduces ferric iron forming ammonium (23.1 %) and nitrous oxide (N2O, 46.5 %) from nitrate. These results are supported with the upregulation of genes coding for proteins responsible for dissimilatory nitrate reduction to ammonium (nrfA), N2O formation (norV, cyt P460), and multiple multiheme c-type cytochromes for ferric iron reduction. Concomitantly, an increase in the N2O-reducing SJA-28 lineage and a decrease in the nitrite-reducing 'Candidatus Methylomirabilis oxyfera' are consistent with the changes in 'Ca. M. nitroreducens' end products. These findings demonstrate the highly flexible physiology of 'Ca. M. nitroreducens' in anaerobic ecosystems with diverse electron acceptor conditions, and further reveals its roles in linking methane oxidation to global biogeochemical cycles. 'Ca. M. nitroreducens' could significantly affect the bioavailability of nitrogen sources as well as the emission of greenhouse gas in natural ecosystems and wastewater treatment plants.

Development of nanobodies targeting hepatocellular carcinoma and application of nanobody-based CAR-T technology.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients' cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative. METHODS: In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation. RESULTS: Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo. CONCLUSIONS: In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

The bioremediation of the typical persistent organic pollutants (POPs) by microalgae-bacteria consortia: A systematic review.

With industrialisation and the rapidly growing agricultural demand, many organic compounds have been leaked into the environment, causing serious damage to the biosphere. Persistent organic pollutants (POPs) are a type of toxic chemicals that are resistant to degradation through normal chemical, biological or photolytic approaches. With their stable chemical structures, POPs can be accumulated in the environment, and transported through wind and water, causing global environmental issues. Many researches have been conducted to remediate POPs contamination using various kinds of biological methods, and significant results have been seen. Microalgae-bacteria consortium is a newly developed concept for biological technology in contamination treatment, with the synergetic effects between microalgae and bacteria, their potential for pollutants degradation can be further released. In this review, two types of POPs (polychlorinated biphenyls and polycyclic aromatic hydrocarbons) are selected as the targeted pollutants to give a systematic analysis of the biodegradation through microalgae and bacteria, including the species selection, the identification of dominant enzymes, as well as the real application performance of the consortia. In the end, some outlooks and suggestions are given to further guide the development of applying microalgae-bacteria consortia in remediating POPs contamination. In general, the coculturing of microalgae and bacteria is a novel and efficient way to fulfil the advanced treatment of POPs in soil or liquid phase, and both monooxygenase and dioxygenase belonging to oxygenase play a vital role in the biodegradation of PCBs and PAHs. This review provides a general guide in the future investigation of biological treatment of POPs.

Deep insights into the biofilm formation mechanism and nitrogen-transformation network in a nitrate-dependent anaerobic methane oxidation biofilm.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process offers a promising solution for simultaneously achieving methane emissions reduction and efficient nitrogen removal in wastewater treatment. Although nitrogen removal at a practical rate has been achieved by n-DAMO biofilm process, the mechanisms of biofilm formation and nitrogen transformation remain to be elucidated. In this study, n-DAMO biofilms were successfully developed in the membrane aerated moving bed biofilm reactor (MAMBBR) and removed nitrate at a rate of 159 mg NO3--N L-1 d-1. The obvious increase in the content of extracellular polymeric substances (EPS) indicated that EPS production was important for biofilm development. n-DAMO microorganisms dominated the microbial community, and n-DAMO bacteria were the most abundant microorganisms. However, the expression of biosynthesis genes for proteins and polysaccharides encoded by n-DAMO archaea was significantly more active compared to other microorganisms, suggesting the central role of n-DAMO archaea in EPS production and biofilm formation. In addition to nitrate reduction, n-DAMO archaea were revealed to actively express dissimilatory nitrate reduction to ammonium and nitrogen fixation. The produced ammonium was putatively converted to dinitrogen gas through the joint function of n-DAMO archaea and n-DAMO bacteria. This study revealed the biofilm formation mechanism and nitrogen-transformation network in n-DAMO biofilm systems, shedding new light on promoting the application of n-DAMO process.

The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments.

BACKGROUND: Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. METHODS: Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells. For this purpose, we initially screened healthy donors and cultured their T cells to obtain a higher proportion of stem cell-like memory T (TSCM) cells, which exhibit robust self-renewal capacity, sustainability and cytotoxicity. To reduce the alloreactivity, the T cells were further edited by double knockout of the T cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes utilizing the CRISPR/Cas9 system. The well-growing and genetically stable universal cells carrying the CAR-moiety were then stored as a stable and unified cell bank. Subsequently, the SDcatcher/GVoptiTag system, which generate an isopeptide bond, was used to covalently connect the purified scFvs of antibody targeting different antigens to the recovered CAR-T cells. RESULTS: The resulting CAR-T cells can perform different functions by specifically targeting various cells, such as the eradication of human immunodeficiency virus type 1 (HIV-1)-latenly-infected cells or elimination of T lymphoma cells, with similar efficiency as the traditional CAR-T cells did. CONCLUSION: Taken together, our strategy allows the production of CAR-T cells more modularization, and makes the quality control and pharmaceutic manufacture of CAR-T cells more feasible.

The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.

Highly efficient degradation of acetaminophen via nano zero-valent iron biochar with periodate system at low temperature.

The development of more efficient advanced oxidation systems for serving various advanced treatment of wastewater is quite necessary and urgent. In this study, a nano-zero valent iron/periodate (nZVI-BC/PI) advanced oxidation system has been constructed, achieving a rapid degradation of acetaminophen (ACT, 1 mg/L) within 1 min (100 % at pH = 11) at low temperature (5℃). This system shows a great degradation in a wide range of pH (1 âˆ¼ 11), improving the pH limitation of PI oxidation system. During the reaction process, ·OH as the main active species collaborate with 1O2, Fe (IV), ·O2- and electron transfer to degrade ACT. In this system, iron ion leaching is low (0.019 mg/L), ACT was effectively degraded (74.36 %∼97.32 %) under different water, moreover, the material has an expected recyclability. The research provides a significant guidance for the advanced treatment of wastewater especially in cold regions.

Combined transcriptomic and metabolomic analyses of temperature response of microalgae using waste activated sludge extracts for promising biodiesel production.

Waste activated sludge (WAS) as one of the major pollutants with a significant annual production, has garnered significant attention regarding its treatment and utilization. If improperly discharged, it not only caused environmental pollution but also led to the wastage of valuable resources. In this study, the microalgae growth and lipid accumulation using waste activated sludge extracts (WASE) under different temperature conditions were investigated. The highest lipid content (59.13%) and lipid productivity (80.41 mg L-1 d-1) were obtained at cultivation temperatures of 10 and 25 °C, respectively. It was found that microalgae can effectively utilize TN/TP/NH4+-N and other nutrients of WASE. The highest utilization rates of TP, TN and NH4+-N were achieved at a cultivation temperature of 10 °C, reaching 84.97, 77.49 and 92.32%, respectively. The algal fatty acids had carbon chains predominantly ranging from C14 to C18, making them suitable for biodiesel production. Additionally, a comprehensive analysis of transcriptomics and metabolomics revealed up-regulation of genes associated with triglyceride assembly, the antioxidant system of algal cells, and cellular autophagy, as well as the accumulation of metabolites related to the tricarboxylic acid (TCA) cycle and lipids. This study offers novel insights into the microscopic mechanisms of microalgae culture using WASE and approaches for the resource utilization of sludge.

New insights into rare earth element-induced microalgae lipid accumulation: Implication for biodiesel production and adsorption mechanism.

A coupling technology for lipid production and adsorption of rare earth elements (REEs) using microalgae was studied in this work. The microalgae cell growth, lipid production, biochemical parameters and lipid profiles were investigated under different REEs (Ce3+, Gd3+and La3+). The results showed that the maximum lipid production was achieved at different concentrations of REEs, with lipid productivities of 300.44, 386.84 and 292.19 mg L-1 d-1 under treatment conditions of 100 µg L-1 Ce3+, 250 µg L-1 Gd3+ and 1 mg L-1 La3+, respectively. Moreover, the adsorption efficiency of Ce3+, Gd3+ and La3+exceeded 96.58 %, 93.06 % and 91.3 % at concentrations of 25-1000 µg L-1, 100-500 µg L-1 and 0.25-1 mg L-1, respectively. In addition, algal cells were able to adsorb 66.2 % of 100 µg L-1 Ce3+, 48.4 % of 250 µg L-1 Gd3+ and 59.9 % of 1 mg L-1 La3+. The combination of extracellular polysaccharide and algal cell wall could adsorb 25.2 % of 100 µg L-1 Ce3+, 44.5 % of 250 µg L-1 Gd3+ and 30.5 % of 1 mg L-1 La3+, respectively. These findings indicated that microalgae predominantly adsorbed REEs through the intracellular pathway. This study elucidates the mechanism of effective lipid accumulation and adsorption of REEs by microalgae under REEs stress conditions. It establishes a theoretical foundation for the efficient microalgae lipid production and REEs recovery from wastewater or waste residues containing REEs.

Generation of a new therapeutic D-peptide that induces the differentiation of acute myeloid leukemia cells through A TLR-2 signaling pathway.

Acute myeloid leukemia (AML) is caused by clonal disorders of hematopoietic stem cells. Differentiation therapy is emerging as an important treatment modality for leukemia, given its less toxicity and wider applicable population, but the arsenal of differentiation-inducing agents is still very limited. In this study, we adapted a competitive peptide phage display platform to search for candidate peptides that could functionally induce human leukemia cell differentiation. A monoclonal phage (P6) and the corresponding peptide (pep-P6) were identified. Both L- and D-chirality of pep-P6 showed potent efficiency in inducing AML cell line differentiation, driving their morphologic maturation and upregulating the expression of macrophage markers and cytokines, including CD11b, CD14, IL-6, IL-1ß, and TNF-α. In the THP-1 xenograft animal model, administration of D-pep-P6 was effective in inhibiting disease progression. Importantly, exposure to D-pep-P6 induced the differentiation of primary human leukemia cells isolated AML patients in a similar manner to the AML cell lines. Further mechanism study suggested that D-pep-P6 induced human leukemia cell differentiation by directly activating a TLR-2 signaling pathway. These findings identify a novel D-peptide that may promote leukemia differentiation therapy.