Microbial mediated remediation of heavy metals toxicity: mechanisms and future prospects.

Heavy metal pollution has become a serious concern across the globe due to their persistent nature, higher toxicity, and recalcitrance. These toxic metals threaten the stability of the environment and the health of all living beings. Heavy metals also enter the human food chain by eating contaminated foods and cause toxic effects on human health. Thus, remediation of HMs polluted soils is mandatory and it needs to be addressed at higher priority. The use of microbes is considered as a promising approach to combat the adverse impacts of HMs. Microbes aided in the restoration of deteriorated environments to their natural condition, with long-term environmental effects. Microbial remediation prevents the leaching and mobilization of HMs and they also make the extraction of HMs simple. Therefore, in this context recent technological advancement allowed to use of bioremediation as an imperative approach to remediate polluted soils. Microbes use different mechanisms including bio-sorption, bioaccumulation, bioleaching, bio-transformation, bio-volatilization and bio-mineralization to mitigate toxic the effects of HMs. Thus, keeping in the view toxic HMs here in this review explores the role of bacteria, fungi and algae in bioremediation of polluted soils. This review also discusses the various approaches that can be used to improve the efficiency of microbes to remediate HMs polluted soils. It also highlights different research gaps that must be solved in future study programs to improve bioremediation efficency.

Endoscopic resection for non-ampullary duodenal subepithelial lesions: a retrospective cohort study.

PURPOSE: This study aimed to assess the safety and efficacy of endoscopic submucosal dissection (ESD) and pre-cutting endoscopic mucosal resection (pEMR) in treating non-ampullary duodenal subepithelial lesions (NADSELs) and to evaluate the clinical utility of endoscopic ultrasound (EUS) before endoscopic resection (ER). METHODS: In this retrospective single-centre cohort study, we compared the clinical outcomes of patients with NADSELs who underwent ESD or pEMR between January 2014 and June 2023. The accuracies of EUS in determining the pathological type and origin of the lesions were evaluated using postoperative histopathology as the gold standard. RESULTS: Overall, 56 patients with NADSELs underwent ER in this study, including 16 and 40 treated with pEMR and ESD, respectively. There were no significant differences between the two groups in terms of en bloc resection rate, complete (R0) resection rate, perioperative complication rate, and postoperative hospital length of stay (P > 0.05). However, the pEMR group had significantly shorter median operational (13.0 min vs. 30.5 min, P < 0.001) and mean fasting (1.9 days vs. 2.8 days, P = 0.006) time and lower median hospital costs (¥12,388 vs. ¥19,579, P = 0.002). The accuracies of EUS in determining the pathological type and origin of the lesions were 76.8% and 94.6%, respectively, compared with histopathological evaluation. CONCLUSIONS: EUS can accurately predict the origin of NADSELs. Suitable lesions determined to originate from the submucosa or more superficial layers using EUS can be treated using pEMR as it shortens the operational and recovery time, reduces hospitalisation costs, and achieves an R0 resection rate similar to ESD.

RNA-binding protein PTENα blocks RIG-I activation to prevent viral inflammation.

A timely inflammatory response is crucial for early viral defense, but uncontrolled inflammation harms the host. Retinoic acid-inducible gene I (RIG-I) has a pivotal role in detecting RNA viruses, yet the regulatory mechanisms governing its sensitivity remain elusive. Here we identify PTENα, an N-terminally extended form of PTEN, as an RNA-binding protein with a preference for the CAUC(G/U)UCAU motif. Using both in vivo and in vitro viral infection assays, we demonstrated that PTENα restricted the host innate immune response, relying on its RNA-binding capacity and phosphatase activity. Mechanistically, PTENα directly bound to viral RNA and enzymatically converted its 5'-triphosphate to 5'-monophosphate, thereby reducing RIG-I sensitivity. Physiologically, brain-intrinsic PTENα exerted protective effects against viral inflammation, while peripheral PTENα restricted host antiviral immunity and, to some extent, promoted viral replication. Collectively, our findings underscore the significance of PTENα in modulating viral RNA- and RIG-I-mediated immune recognition, offering potential therapeutic implications for infectious diseases.

Integrated physiological, intestinal microbiota, and metabolomic responses of adult zebrafish (Danio rerio) to subacute exposure to antimony at environmentally relevant concentrations.

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities' composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the "microbiota-intestine-brain axis" and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies.

Tumor-Associated Monocytes Reprogram CD8+ T Cells into Central Memory-Like Cells with Potent Antitumor Effects.

CD8+ T cells are critical for host antitumor responses, whereas persistent antigenic stimulation and excessive inflammatory signals lead to T cell dysfunction or exhaustion. Increasing early memory T cells can improve T cell persistence and empower T cell-mediated tumor eradication, especially for adoptive cancer immunotherapy. Here, it is reported that tumor-associated monocytes (TAMos) are highly correlated with the accumulation of CD8+ memory T cells in human cancers. Further analysis identifies that TAMos selectively reprogram CD8+ T cells into T central memory-like (TCM-like) cells with enhanced recall responses. L-NMMA, a pan nitric oxide synthase inhibitor, can mitigate TAMo-mediated inhibition of T cell proliferation without affecting TCM-like cell generation. Moreover, the modified T cells by TAMo exposure and L-NMMA treatment exhibit long-term persistence and elicit superior antitumor effects in vivo. Mechanistically, the transmembrane protein CD300LG is involved in TAMo-mediated TCM-like cell polarization in a cell-cell contact-dependent manner. Thus, the terminally differentiated TAMo subset (CD300LGhighACElow) mainly contributes to TCM-like cell development. Taken together, these findings establish the significance of TAMos in boosting T-cell antitumor immunity.

Development of a DNA aptamer targeting IDO1 with anti-tumor effects.

Immune checkpoint blockade has become an effective approach to reverse the immune tolerance of tumor cells. Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently upregulated in many types of cancers and contributes to the establishment of an immunosuppressive cancer microenvironment, which has been thought to be a potential target for cancer therapy. However, the development of IDO1 inhibitors for clinical application is still limited. Here, we isolated a DNA aptamer with a strong affinity and inhibitory activity against IDO1, designated as IDO-APT. By conjugating with nanoparticles, in situ injection of IDO-APT to CT26 tumor-bearing mice significantly suppresses the activity of regulatory T cells and promotes the function of CD8+ T cells, leading to tumor suppression and prolonged survival. Therefore, this functional IDO1-specific aptamer with potent anti-tumor effects may serve as a potential therapeutic strategy in cancer immunotherapy. Our data provide an alternative way to target IDO1 in addition to small molecule inhibitors.

Development of a modularized aptamer targeting the nuclear T-cell suppressor PAC1.

Aptamers associated with cancer targeting therapy are commonly focused on cell membrane proteins; however, the study of intracellular, particularly, nuclear proteins is limited. The nuclear phosphatase PAC1 has been reported to be a potential T cell-related immunotherapeutic target. Here, we identified an aptamer, designated as PA5, with high affinity and specificity for PAC1 through the systematic evolution of ligands by exponential enrichment (SELEX) procedure. We then developed a dual-module aptamer PAC1-AS consisting of a cell-internalizing module and a targeting module, which can recognize PAC1 in the nucleus under physiological conditions. This modularized aptamer raises the possibility of manipulating endosomes and provides insights into the exploration and development of an efficient cancer immunotherapy approach.

Experimental Investigation of Eco-Friendly Anhydrous Calcium Sulfate Whisker and Waste Cooking Oil Compound Modified Asphalt Mixture.

In recent years, waste material recycling and reuse have attracted great interest as environmentally friendly modifiers to improve asphalt pavement performance. In this study, anhydrous calcium sulfate whiskers (ACSW), synthesized using phosphogypsum waste, and waste cooking oil (WCO), one of the most prevalent waste oils, were used together as modifiers to create an environmentally friendly asphalt mixture. In particular, WCO was used to compensate for the negative effects of ACSW on asphalt mixture performance at low temperatures. A variety of ACSW and WCO compound-modified asphalt mixtures were fabricated. High-temperature stability, medium-temperature fatigue, low-temperature anti-cracking, moisture susceptibility, repeated freeze-thaw, and long-term aging tests were conducted to comprehensively evaluate the pavement performance. Compared to the base asphalt mixture, the compound-modified asphalt mixtures were demonstrated to have better high- and low-temperature, moisture susceptibility, fatigue, anti-freezing, and anti-aging properties, especially for the 6%ACSW and 2%WCO compound-modified asphalt mixture. Therefore, the 6%ACSW and 2%WCO compound-modified asphalt mixture was ultimately selected for use in construction, as this mixture can meet the requirements for regions with cold winters and hot summers.

The phosphatase PAC1 acts as a T cell suppressor and attenuates host antitumor immunity.

Cancer cells subvert immune surveillance through inhibition of T cell effector function. Elucidation of the mechanism of T cell dysfunction is therefore central to cancer immunotherapy. Here, we report that dual specificity phosphatase 2 (DUSP2; also known as phosphatase of activated cells 1, PAC1) acts as an immune checkpoint in T cell antitumor immunity. PAC1 is selectively upregulated in exhausted tumor-infiltrating lymphocytes and is associated with poor prognosis of patients with cancer. PAC1hi effector T cells lose their proliferative and effector capacities and convert into exhausted T cells. Deletion of PAC1 enhances immune responses and reduces cancer susceptibility in mice. Through activation of EGR1, excessive reactive oxygen species in the tumor microenvironment induce expression of PAC1, which recruits the Mi-2ß nucleosome-remodeling and histone-deacetylase complex, eventually leading to chromatin remodeling of effector T cells. Our study demonstrates that PAC1 is an epigenetic immune regulator and highlights the importance of targeting PAC1 in cancer immunotherapy.

The Effects of Trace Yb Doping on the Electrochemical Performance of Li-Rich Layered Oxides.

Layered lithium-rich cathode materials are one of the most promising cathode materials owing to their higher mass energy density than the commercial counterparts. A series of trace Yb-doped lithium-rich cathode materials Li1.2 Mn0.54 Ni0.13 Co0.13-x Ybx O2 (0≤x≤0.050) were synthesized and the effects were investigated by XRD, X-ray photoelectron spectroscopy, and high-resolution TEM. The participation of Yb ions in electrochemical reactions and the larger binding energy of Yb-O than M-O (M=Mn, Ni, Co), which expands the lithium layer spacing and stabilizes the oxygen stacking, resulted in excellent performance of materials doped with a limited Yb content (x≤0.005). However, higher doping amounts (x>0.005) significantly increased the charge-transfer impedance and led to a sharp deterioration in electrochemical performance. The reason lies in the large difference in ionic radius between the transition metals (Mn, Co, and Ni) and Yb. There is an upper limit to the amount of Yb ions in the lattice. If the amount of Yb is higher than the limit, excess Yb ions enter the Li layers instead of staying in the transition-metal layers or even segregate on the surface and form electrochemically inert oxides.

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm.

The objective of this study was to screen for novel quorum-sensing inhibitors (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm formation. Six of 46 active components found in TCMs were identified as putative QSIs based on molecular docking studies. Of these, three compounds inhibited biofilm formation by Pseudomonas aeruginosa and Stenotrophomonas maltophilia at a concentration of 200 µM. A fourth compound (emodin) significantly inhibited biofilm formation at 20 µM and induced proteolysis of the quorum-sensing signal receptor TraR in Escherichia coli at a concentration of 3-30 mM. Emodin also increased the activity of ampicillin against P. aeruginosa. Therefore, emodin might be suitable for development into an antivirulence and antibacterial agent.

Construction of a Monascus purpureus mutant showing lower citrinin and higher pigment production by replacement of ctnA with pks1 without using vector and resistance gene.

Monascus products are used as both natural colorants and food additives all over the world. However, its safety is really an issue because of the presence of citrinin, which is considered to be hepatotoxic and nephrotoxic. Therefore, the objective of the present study was to develop an approach for using a fragment of pigment-related gene pks1 to replace citrinin-activator gene ctnA. The character of citrinin antibacterial activity to Bacillus subtilis was used for primary screening of transformants based on the foundation that the inhibition zone formed around the mutant colonies with low citrinin products will become smaller. The selected mutants were then further confirmed by polymerase chain reaction and high-performance liquid chromatography methods. During all of the processes, antibiotic markers and vectors were avoided. The results showed that the citrinin products of mutants were reduced to 42%, while the pigment products were improved to 33.9%, respectively, over those of the wild-type strains.