Pyroptosis in health and disease: mechanisms, regulation and clinical perspective.

Pyroptosis is a type of programmed cell death characterized by cell swelling and osmotic lysis, resulting in cytomembrane rupture and release of immunostimulatory components, which play a role in several pathological processes. Significant cellular responses to various stimuli involve the formation of inflammasomes, maturation of inflammatory caspases, and caspase-mediated cleavage of gasdermin. The function of pyroptosis in disease is complex but not a simple angelic or demonic role. While inflammatory diseases such as sepsis are associated with uncontrollable pyroptosis, the potent immune response induced by pyroptosis can be exploited as a therapeutic target for anti-tumor therapy. Thus, a comprehensive review of the role of pyroptosis in disease is crucial for further research and clinical translation from bench to bedside. In this review, we summarize the recent advancements in understanding the role of pyroptosis in disease, covering the related development history, molecular mechanisms including canonical, non-canonical, caspase 3/8, and granzyme-mediated pathways, and its regulatory function in health and multiple diseases. Moreover, this review also provides updates on promising therapeutic strategies by applying novel small molecule inhibitors and traditional medicines to regulate pyroptosis. The present dilemmas and future directions in the landscape of pyroptosis are also discussed from a clinical perspective, providing clues for scientists to develop novel drugs targeting pyroptosis.

Pyrazine-based iron metal organic frameworks (Fe-MOFs) with modulated O-Fe-N coordination for enhanced hydroxyl radical generation in Fenton-like process.

Rational design of coordination environment of Fe-based metal-organic frameworks (Fe-MOFs) is still a challenge in achieving enhanced catalytic activity for Fenten-like advanced oxidation process. Here in, novel porous Fe-MOFs with modulated O-Fe-N coordination was developed by configurating amino terephthalic acid (H2ATA) and pyrazine-dicarboxylic acid (PzDC) (Fe-ATA/PzDC-7:3). PzDC ligands introduce pyridine-N sites to form O-Fe-N coordination with lower binding energy, which affect the local electronic environment of Fe-clusters in Fe-ATA, thus decreased its interfacial H2O2 activation barrier. O-Fe-N coordination also accelerate Fe(II)/Fe(III) cycling of Fe-clusters by triggering the reactive oxidant species mediated Fe(III) reduction. As such, Fe-ATA/PzDC-7:3/H2O2 system exhibited excellent degradation performance for typical antibiotic sulfamethoxazole (SMX), in which the steady-state concentration of hydroxyl radical (OH) was 1.6 times higher than that of unregulated Fe-ATA. Overall, this study highlights the role of O-Fe-N coordination and the electronic environment of Fe-clusters on regulating Fenton-like catalytic performance, and provides a platform for precise engineering of Fe-MOFs.

Efficient Preparation of a Magnetic Helical Carbon Nanomotor for Targeted Anticancer Drug Delivery.

The applications of nanomotors in the biomedical field have been attracting extensive attention. However, it remains a challenge to fabricate nanomotors in a facile way and effectively load drugs for active targeted therapy. In this work, we combine the microwave heating method and chemical vapor deposition (CVD) to fabricate magnetic helical nanomotors efficiently. The microwave heating method can accelerate intermolecular movement, which converts kinetic energy into heat energy and shortens the preparation time of the catalyst used for carbon nanocoil (CNC) synthesis by 15 times. Fe3O4 nanoparticles are in situ nucleated on the CNC surface by the microwave heating method to fabricate magnetically driven CNC/Fe3O4 nanomotors. In addition, we achieved precise control of the magnetically driven CNC/Fe3O4 nanomotors through remote manipulation of magnetic fields. Anticancer drug doxorubicin (DOX) is then efficiently loaded onto the nanomotors via π-π stacking interactions. Finally, the drug-loaded CNC/Fe3O4@DOX nanomotor can accurately accomplish cell targeting under external magnetic field control. Under short-time irradiation of near-infrared light, DOX can be quickly released onto target cells to effectively kill the cells. More importantly, CNC/Fe3O4@DOX nanomotors allow for single-cell or cell-cluster-targeted anticancer drug delivery, providing a dexterous platform to potentially perform many medically relevant tasks in vivo. The efficient preparation method and application in drug delivery are beneficial for future industrial production and provide inspiration for advanced micro/nanorobotic systems using the CNC as a carrier for a wide range of biomedical applications.

Pilot investigation on biostability of drinking water distribution systems under water source switching.

Water quality deterioration of drinking water distribution systems (DWDSs) caused by water source switching has been reported previously. However, systematic investigation of the biostability of DWDS under water source switching is limited. Aged pipes, including three commonly used pipe materials dug out from a practical DWDS, were used to systematically investigate the biofilm stability mechanism of DWDS under water source switching to quality-improved water. An increase in adenosine triphosphate (ATP) concentration in the bulk water during the initial stage of the switching period was observed, indicating the risk of biofilm release through aged pipe surfaces after water source switching. Sloughing of biofilms might contribute to temporary instability. From day 35, the ATP concentration in the polyethylene (PE) and plastic stainless steel composite (PS) pipes were maintained at approximately 2.40 and 2.56 ng/L, respectively. In contrast, the ATP concentration in the ductile iron (DI) pipes was higher, at approximately 3.43 ng/L from day 42. The water quality variation could cause areas of the biofilm to slough and reduce the biomass of biofilm, causing partial alteration of the microbial community. 16S rRNA gene amplicon sequencing-based functional prediction revealed that the biofilm could increase the abundance of chlorine-resistant bacteria attributed to the increase in Pseudomonas and Methylobacterium after switching to quality-improved water. Moreover, the profiles of specific pathways linked to human diseases, antibiotic resistance, and antibiotic biosynthesis revealed that the safety of the biofilm could improve after switching to quality-improved water. KEY POINTS: • The PE and PS biofilm showed improved resistance to water quality perturbation. • Greater number of Methylobacterium was found in the biofilm after water source switching. • 3.16S gene-based metagenomics prediction revealed that the safety of the biofilm under water source switching.

Characteristics of biostability of drinking water in aged pipes after water source switching: ATP evaluation, biofilms niches and microbial community transition.

Delivering quality-changed water often contributes to the biological instability of drinking water distribution systems (DWDS). However, the potential effects of quality-changed water on the biostability within DWDS are not well understood, especially after water switching to quality-improved water. The objective of this study was to investigate the effects of quality-improved water on DWDS, focusing on the stability of biofilm. The practical aged-pipe was assembled into pipe reactors to simulate the effect of switching to quality-improve water. The adenosine triphosphate (ATP) concentration of bulk water in the pipe reactors increased from ∼1.2 ng/L to almost above 5 ng/L when fed water switching to TP 2. Biomass quantified by measuring ATP concentration confirmed that the risk of biofilm release through aged cast-iron (CI) pipe surfaces after water source switching. The changes in water characteristics due to quality-improved water source could cause bacteria release in DWDS at the initial period (at the first 7 days). However, the DWDS can establish the new stable phase after 42 days. Over time, biomass in the bulk water of the distribution system decreased significantly (The ATP concentration in the bulk maintains around 3 ng/L) after 42 days, indicating the improvement of water quality. The biofilm was dominated by bacteria related to iron-cycling process, and at the genus level, Desulfovibrio had the highest relative abundance, however, it decreased significantly (from 48% to 9.3%) after water source switching. And there was a slightly increase in the fraction of iron-oxidizing bacteria (IOB) and siderophore-producing bacteria (SPB), but a relatively higher increase in nitrate-reducing bacteria (NRB), nitrobacteria (NOB), and iron-reducing bacteria (IRB) was observed. Taken together, these results and the corrosion morphology, indicate that pipe biofilm and corrosion were chemically and microbially stable after re-stability under water source switching. In addition, the bulk water environment showed a marked decrease in selected bacteria at genus level, including pathogenic species, indicating the improvement of quality in drinking water.

Biotransformation of halophenols into earthy-musty haloanisoles: Investigation of dominant bacterial contributors in drinking water distribution systems.

Microorganisms in drinking water distribution systems (DWDSs) can O-methylate toxic halophenols (HPs) into earthy-musty haloanisoles (HAs). However, the dominant HA-producing bacterial species and their O-methylation properties are still unknown. In this study, eight bacterial strains from DWDS were isolated and the community abundances of the related genera in bulk water and biofilms as well as their O-methylation properties were investigated. Among the genera discovered in this study, Sphingomonas and Pseudomonas are dominant and play important roles in DWDSs. All bacteria could simultaneously convert five HPs to the corresponding HAs. Two Sphingomonas ursincola strains mainly produced 2,3,6-trichloroanisole (2,3,6-TCA) (2.48 × 10-9-1.18 × 10-8 ng/CFU), 2,4,6-trichloroanisole (2,4,6-TCA) (8.12 × 10-10-3.11 × 10-9 ng/CFU) and 2,4,6-tribromoanisole (2,4,6-TBA) (2.95 × 10-9-3.21 × 10-9 ng/CFU), while two Pseudomonas moraviensis strains preferred to generate 2-monochloroanisole (2-MCA) (1.19 × 10-9-3.70 × 10-9 ng/CFU) and 2,4-dichloroanisole (2,4-DCA) (3.81 × 10-9-1.20 × 10-8 ng/CFU). Among the chloramphenicol-susceptible strains, four strains contained inducible O-methyltransferases (OMTs), while the O-methylations of the others were expressed constitutively. All bacteria could use S-adenosyl methionine as methyl donor. Potential taste and odor (T & O) risks of five HAs in DWDS followed an order of 2,4,6-TBA > 2,4,6-TCA > 2,3,6-TCA > 2,4-DCA > 2-MCA. The recommended 2,4,6-TCP criteria for T & O control is 0.003-0.07 mg/L.

A novel method: using an adenosine triphosphate (ATP) luminescence-based assay to rapidly assess the biological stability of drinking water.

The rapid and credible evaluations of the microbial stability of a drinking water distribution system (DWDS) are of great significance for ensuring the safety of drinking water and predicting microbial pollution. Conventional biostability assessment methods mainly focus on bacterial regrowth or evaluation of the level of nutrients that support bacterial regrowth. However, such methods are time-consuming and have many limitations. An adenosine triphosphate (ATP) assay can rapidly measure all active microorganisms and is known to be a useful method to assess the microbial activity of drinking water. The measurement of ATP has been used for more than a decade in the field of drinking water research. This article reviews the application of an ATP luminescence-based method to assess the biostability of drinking water and discusses the feasibility of ATP measurement as a parameter for quickly evaluating this criterion. ATP measurement will help researchers and water managers better monitor the biological stability of drinking water from the source to the consumer's tap. This review covers the: (1) principle and application of the ATP measurement in drinking water quality assessment; (2) comparison of the merits and demerits of several methods for evaluating the biostability of drinking water; (3) discussions on using ATP measurement in evaluating biostability; and (4) improvements in the use of ATP measurement in evaluating biostability. At the end of this review, recommendations were given for better application of the ATP measurement as a parameter for monitoring the microbial quality of drinking water.