Unveiling the distribution characteristics of rpf-like genes and indigenous resuscitation promoting factor production in PCB-contaminated soils.

Resuscitation promoting factors (Rpfs), known for their anti-dormancy cytokine properties, have been extensively investigated in the medical field. Although the Rpf from Micrococcus luteus has been successfully utilized to resuscitate and stimulate microbial populations for the degradation of polychlorinated biphenyls (PCBs), the presence of indigenous Rpf homologs in PCB-contaminated soils has not been established. In this study, the distribution characteristics of rpf-like genes and indigenous strain capable of producing Rpf in PCB-contaminated soils were explored. The results revealed the widespread presence of Rpf-like domains and their associated genes, particularly in close association with heavy metals and PCBs. The rpf-like genes were predominantly found in Proteobacteria and displayed a positive correlation with genes involved in PCB degradation and viable but non-culturable (VBNC) formation. Notably, the recombinant Rpf-Ac protein derived from the indigenous strain Achromobacter sp. HR2 exhibited muralytic activity and demonstrated significant efficacy in resuscitating the growth of VBNC cells, while also stimulating the growth of normal cells. These findings shed light on the prevalent presence of Rpf homologs in PCB-contaminated soils and their potential to resuscitate functional populations in the VBNC state, thereby enhancing in situ bioremediation.

Fabrication of High Surface Area Fe/Fe3 O4 with Enhanced Performance for Electrocatalytic Nitrogen Reduction Reaction.

The development of high-efficient and large-scale non-precious electrocatalysts to improve sluggish reaction kinetics plays a key role in enhancing electrocatalytic nitrogen reduction reaction (NRR) for ammonia production under mild condition. Herein, Fe3 O4 and Fe supported by porous carbon (denoted as Fe/Fe3 O4 /PC-800) composite with a high specific surface area of 1004.1 m2 g-1 was prepared via a simple template method. On one hand, the high surface area of Fe/Fe3 O4 /PC-800 provides a large area to enhance N2 adsorption and promote more protons and electrons to accelerate the reaction, thereby greatly improving the dynamics. On the other hand, mesoporous Fe/Fe3 O4 /PC-800 provides high electrochemically active surface area for promoting the occurrence of catalytic kinetics. As a result, Fe/Fe3 O4 /PC-800 exhibited significantly enhanced NRR performance with an ammonia yield of 31.15 µg h-1 mg-1 cat. and faraday efficiency of 22.26 % at -0.1 V vs. reversible hydrogen electrode (RHE). This study is expected to provide a new strategy for the synthesis of catalysts with large specific area and pave the way for the foundational research in NRR.

Oxidative dehalogenation and mineralization of polychlorinated biphenyls by a resuscitated strain Streptococcus sp. SPC0.

Most functional microorganisms cannot be cultivated due to entering a viable but non-culturable (VBNC) state, which limits the characterization and application of polychlorinated biphenyl (PCB)-degrading strains. Resuscitating VBNC bacteria could provide huge candidates for obtaining high-efficient PCB degraders. However, limited studies have focused on the ability of resuscitated strains for PCBs degradation. In the present study, whole-genome analysis of a resuscitated strain SPC0, and its performances in degradation of three prevalent PCB congeners (PCBs 18, 52 and 77) were investigated. The results indicate that the strain SPC0 belonged to the genus Streptococcus, possessed the degradation potential for aromatic xenobiotics. The SPC0 could effectively degrade PCBs 18 and 52, but exhibited lower degradation efficiency of PCB 77. Degradation of PCBs 18 and 52 could be fitted well by zero-order model, whereas the fittest model for PCB 77 degradation was pseudo second-order kinetics. The bph genes expression, chloride ions release and degradation metabolites identification, suggest that SPC0 possessed the capability of oxidative dehalogenation and mineralization of PCBs. Interestingly, SPC0 can degrade PCBs via the bph-encoded biphenyl pathway, and further mineralize metabolite dichlorobenzoate via protocatechuate pathway. This study is the first to show that a strain belonging to genus Streptococcus possessed PCB-degrading capability, which uncovered the powerful potential of resuscitated strains for bioremediation of PCB-contaminated sites.

[Cloning and function analysis of chalcone isomerase gene and chalcone synthase gene in Lonicera macranthoides].

In order to explore the functions of genes of key rate-limiting enzymes chalcone isomerase(CHI) and chalcone synthase(CHS) in the biosynthesis of flavonoids in Lonicera macranthoides, this study screened and cloned the cDNA sequences of CHI and CHS genes from the transcriptome data of conventional variety and 'Xianglei' of L. macranthoides. Online bioinformatics analysis software was used to analyze the characteristics of the encoded proteins, and quantitative reverse-transcription polymerase chain reaction(qRT-PCR) to detect the expression of CHI and CHS in different parts of the varieties at different flowering stages. The content of luteo-loside was determined by high performance liquid chromatography(HPLC) and the correlation with the expression of the two genes was analyzed. The results showed that the CHI and CHS of the two varieties contained a 627 bp and 1170 bp open reading frame(ORF), respectively, and the CHI protein and CHS protein were stable, hydrophilic, and non-secretory. qRT-PCR results demonstrated that CHI and CHS of the two varieties were differentially expressed in stems and leaves at different flowering stages, particularly the key stages. Based on HPLC data, luteoloside content was in negative correlation with the relative expression of the genes. Thus, CHI and CHS might regulate the accumulation of flavonoids in L. macranthoides, and the specific functions should be further studied. This study cloned CHI and CHS in L. macranthoides and analyzed their expression for the first time, which laid a basis for investigating the molecular mechanism of the differences in flavonoids such as luteoloside in L. macranthoides and variety breeding.

Human umbilical cord mesenchymal stem cell exosomes alleviate sepsis-associated acute kidney injury via regulating microRNA-146b expression.

Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Ex) are a promising tool for the repair of acute kidney injury (AKI) caused by cisplatin and ischemia/reperfusion. However, the roles of hucMSC-Ex in sepsis-associated AKI repair and its mechanism are largely unknown. Hence, we constructed a sepsis model through cecal ligation and puncture (CLP), testing the benefits of hucMSC-Ex in the sepsis in terms of survival rate, serum renal markers levels, morphological changes and apoptosis. Immunohistochemistry staining and immunofluorescence assay were used to investigate the role of NF-κB activity in the repair of sepsis-associated AKI with hucMSC-Ex. HK-2 cells were transfected with microRNA-146b (miR-146b) mimics and inhibitors, respectively, and the regulatory effect of miR-146b on NF-κB activity was studied. We found that hucMSC-Ex treatment significantly decreased the serum creatinine (Cr) and blood urea nitrogen (BUN) levels, ameliorated the morphological damage and inhibited renal tubular cells apoptosis. More importantly, the survival rate at 72 h was 28% in CLP group and 45% in hucMSC-Ex group, respectively. Treatment with hucMSC-Ex improved survival in mice with sepsis. These effects of hucMSC-Ex were mediated by the inhibition of NF-κB activity and the lessening of pro-inflammatory response. Furthermore, hucMSC-Ex significantly increased miR-146b expression in kidney tissues. Conversely, interleukin (IL)-1 receptor-associated kinase (IRAK1) level, which is the target gene of miR-146b, clearly decreased in hucMSC-Ex group. In brief, this study showed that treatment with hucMSC-Ex decreased IRAK1 expression through the up-regulation of miR-146b level, led to the inhibition of NF-κB activity, and eventually alleviated sepsis-associated AKI and improved survival in mice with sepsis. HucMSC-Ex may be a novel therapeutic agent for the reduction of sepsis-associated AKI.

Electrospinning Ag-TiO2 Nanorod-Loaded Air Treatment Filters and Their Applications in Air Purification.

The efficient treatment of the problem of air pollution is a practical issue related to human health. The development of multi-functional air treatment filters, which can remove various kinds of pollutants, including particulate matter (PM) and organic gases, is a tireless pursuit aiming to address the actual needs of humans. Advanced materials and nano-manufacturing technology have brought about the opportunity to change conventional air filters for practical demands, with the aim of achieving the high-efficiency utilization of photons, a strong catalytic ability, and the synergetic degradation of multi-pollutants. In this work, visible-responding photocatalytic air treatment filters were prepared and combined with a fast and cost-effective electrospinning process. Firstly, we synthesized Ag-loaded TiO2 nanorod composites with a controlled size and number of loaded Ag nanoparticles. Then, multi-functional air treatment filters were designed by loading catalysts on electrospinning nanofibers combined with a programmable brush. We found that such Ag-TiO2 nanorod composite-loaded nanofibers displayed prominent PM filtration (~90%) and the degradation of organic pollutants (above 90%). The superior performance of purification could be demonstrated in two aspects. One was the improvement of the adsorption of pollutants derived from the increase of the specific surface area after the loading of catalysts, and the other was the plasmonic hot carriers, which induced a broadening of the optical absorption in the visible light range, meaning that many more photons were utilized effectively. The designed air treatment filters with synergistic effects for eliminating both PM and organic pollutants have promising potential for the future design and application of novel air treatment devices.

Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function.

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague-Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1ß, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.

A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer.

PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3'-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility.

The polymorphic terminal-loop of pre-miR-1307 binding with MBNL1 contributes to colorectal carcinogenesis via interference with Dicer1 recruitment.

Colorectal cancer (CRC) is one of the most common malignancies in the world. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in microRNA genes (miRSNPs) are involved in the occurrence of cancers. However, the relationship between the miRSNPs within the terminal-loops of microRNA precursors and the development of CRC is still largely unknown. In this study, we found that a miRSNP rs7911488 T>C in the terminal-loop of pre-miR-1307 was significantly associated with the occurrence of CRC. The C allele of rs7911488 is more prevalent in CRC patients than in healthy controls (P < 0.001), and this C allele prevalence is related to low level of miR-1307 expression. A RNA-binding protein MBNL1 binds with a 'UGCUGC' motif in the terminal-loop of the C-allelic pre-miR-1307 and blocks Dicer processing, resulting in downregulation of miR-1307 expression. Consequently, the antiapoptosis protein Bcl2, which is a direct target of miR-1307, is overexpressed in CRC. Furthermore, MBNL1 participates in processing of both C-allelic and T-allelic pre-miR-1307. In summary, our results show that rs7911488 C-allelic pre-miR-1307 binds to MBNL1 and infers with Dicer processing, leading to reduced miR-1307 and increased Bcl2 expression, thus representing an important process in the initiation of CRC.

Five functional polymorphisms of B7/CD28 co-signaling molecules alter susceptibility to colorectal cancer.

Polymorphisms within the 3'-untranslated region (3'-UTR) of genes have been proved to contribute to the risk of cancers. Here, we determined 16 putatively functional polymorphisms in the 3'-UTR of 11 B7/CD28 genes in 382 colorectal cancer patients and 714 healthy controls. Statistical analysis revealed that ICOS rs4404254-C-allele carriers (p=0.0014), rs1559931-A-allele carriers (p=0.0027), and rs4675379-C-allele carriers (p=0.026) were significantly fewer in patients than those in controls. B7-H4-rs13505-GG homozygotes were more prevalent in patients (p=0.03). CD80-rs7628626-GT was apparently less in the patients with lymph node metastasis (p=0.004) or in advanced stage (p=0.037). Furthermore, we found that these polymorphisms impacted the regulatory role of miR-21-3p, miR-186-5p, miR-323b-5p, miR-1207-5p, miR-1279, miR-2117, and miR-3692-3p in the expression of the B7/CD28 molecules. Our findings suggest that rs7628626, rs13505, rs4404254, rs1559931, and rs4675379, through disrupting the regulatory role of miRNAs in the expression of B7/CD28 molecules, contribute to the occurrence and progress of colorectal cancer.

Small extracellular vesicles: Non-negligible vesicles in tumor progression, diagnosis, and therapy.

Small extracellular vesicles (sEVs) such as exosomes are nanoscale membranous particles (<200 nm) that have emerged as crucial targets for liquid biopsy and as promising drug delivery vehicles. They play a significant role in tumor progression as intercellular messengers. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment. This article reviews recent studies on sEVs in oncology and explores their potential as biomarkers and drug delivery vehicles. Following tumorigenesis, sEVs in the tumor microenvironment (TME) and circulatory system undergo modifications to regulate various events in the TME, including angiogenesis, epithelial-mesenchymal transition (EMT), and tumor immunity, with either pro- or anti-tumor effects. sEVs have been investigated for use as diagnostic and prognostic biomarkers for a variety of tumors, including lung cancer, melanoma, breast cancer, prostate cancer, and hepatocellular carcinoma. sEVs can be used for cancer therapy by packaging drugs or proteins into them through pre- and post-isolation modification techniques. The clinical trials of sEVs as biomarkers and drug carriers are also summarized. Finally, the challenges in the use of sEVs are described and the possible approaches to tackling them are suggested. Overall, sEVs will advance the precision cancer medicine and has shown great potential in clinical applications.

Nanomaterials-induced programmed cell death: Focus on mitochondria.

Nanomaterials are widely utilized in several domains, such as everyday life, societal manufacturing, and biomedical applications, which expand the potential for nanomaterials to penetrate biological barriers and interact with cells. Multiple studies have concentrated on the particular or improper utilization of nanomaterials, resulting in cellular death. The primary mode of cell death caused by nanotoxicity is programmable cell death, which includes apoptosis, ferroptosis, necroptosis, and pyroptosis. Based on our prior publications and latest research, mitochondria have a vital function in facilitating programmed cell death caused by nanomaterials, as well as initiating or transmitting death signal pathways associated with it. Therefore, this review takes mitochondria as the focal point to investigate the internal molecular mechanism of nanomaterial-induced programmed cell death, with the aim of identifying potential targets for prevention and treatment in related studies.

Glycyrrhizin Protects Submandibular Gland Against Radiation Damage by Enhancing Antioxidant Defense and Preserving Mitochondrial Homeostasis.

Aims: Radiotherapy inevitably causes radiation damage to the salivary glands (SGs) in patients with head and neck cancers (HNCs). Excessive reactive oxygen species (ROS) levels and imbalanced mitochondrial homeostasis are serious consequences of ionizing radiation in SGs; however, there are few mitochondria-targeting therapeutic approaches. Glycyrrhizin is the main extract of licorice root and exhibits antioxidant activity to relieve mitochondrial damage in certain oxidative stress conditions. Herein, the effects of glycyrrhizin on irradiated submandibular glands (SMGs) and the related mechanisms were investigated. Results: Glycyrrhizin reduced radiation damage in rat SMGs at both the cell and tissue levels, and promoted saliva secretion in irradiated SMGs. Glycyrrhizin significantly downregulated high-mobility group box-1 protein (HMGB1) and toll-like receptor 5 (TLR5). Moreover, glycyrrhizin significantly suppressed the increases in malondialdehyde and glutathione disulfide (GSSG) levels; elevated the activity of some critical antioxidants, including superoxide dismutase, catalase, glutathione peroxidase, and glutathione (GSH); and increased the GSH/GSSG ratio in irradiated cells. Importantly, glycyrrhizin effectively enhanced thioredoxin-2 levels and scavenged mitochondrial ROS, inhibited the decline in mitochondrial membrane potential, improved adenosine triphosphate synthesis, preserved the mitochondrial ultrastructure, activated the proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)/nuclear respiratory factor 1/2 (NRF1/2)/mitochondrial transcription factor A (TFAM) signaling pathway, and inhibited mitochondria-related apoptosis in irradiated SMG cells and tissues. Innovation: Radiotherapy causes radiation sialadenitis in HNC patients. Our data suggest that glycyrrhizin could be a mitochondria-targeted antioxidant for the prevention of radiation damage in SGs. Conclusion: These findings demonstrate that glycyrrhizin protects SMGs from radiation damage by downregulating HMGB1/TLR5 signaling, maintaining intracellular redox balance, eliminating mitochondrial ROS, preserving mitochondrial homeostasis, and inhibiting apoptosis.

Isorhamnetin alleviates ferroptosis-mediated colitis by activating the NRF2/HO-1 pathway and chelating iron.

Ferroptosis of intestinal epithelial cells (IECs) had been identified as a key factor in the development of ulcerative colitis (UC). Therefore, targeted inhibition of ferroptosis may provide a new strategy for the treatment of UC. Isorhamnetin (ISO) was an O-methylated flavonol with therapeutic effects on a variety of diseases, such as cardiovascular disease, neurological disorders and tumors. However, the role and mechanism of ISO in ferroptosis and associated colitis were rarely investigated. In this study, we demonstrated that ISO could effectively alleviate intestinal inflammation by inhibiting ferroptosis of IECs in DSS-induced mice. Moreover, our results shown that ISO acted as a potent and common ferroptosis inhibitor in multiple human and murine cell lines. Mechanistically, ISO inhibited ferroptosis independent of its previously reported targets MEK1 and PI3K, but alleviated oxidative stress by targeting and activating NRF2. Furthermore, ISO could also directly chelate iron to hinder ferroptosis. In conclusion, our study indicated that ISO as a novel potential ferroptosis inhibitor, providing a promising therapeutic strategy for ferroptosis-related colitis.

Identification of a targeted ACSL4 inhibitor to treat ferroptosis-related diseases.

Ferroptosis is a form of iron-dependent, lipid peroxidation-driven regulatory cell death that has been implicated in the pathogenesis of multiple diseases, including organ injury, ischemia/reperfusion, and neurodegenerative diseases. However, inhibitors that directly and specifically target ferroptosis are not yet available. Here, we identify the compound AS-252424 (AS) as a potent ferroptosis inhibitor through kinase inhibitor library screening. Our results show that AS effectively inhibits lipid peroxidation and ferroptosis in both human and mouse cells. Mechanistically, AS directly binds to the glutamine 464 of ACSL4 to inhibit its enzymatic activity, resulting in the suppression of lipid peroxidation and ferroptosis. By using nanoparticle-based delivery systems, treatment with AS-loaded nanoparticles effectively alleviate ferroptosis-mediated organ injury in mouse models, including kidney ischemia/reperfusion injury and acute liver injury (ALI). Thus, our results identify that AS is a specific and targeted inhibitor of ACSL4 with remarkable antiferroptosis function, providing a potential therapeutic for ferroptosis-related diseases.

Copper(II)-Based Nano-Regulator Correlates Cuproptosis Burst and Sequential Immunogenic Cell Death for Synergistic Cancer Immunotherapy.

Immunogenic cell death (ICD) of tumor cells serves as a crucial initial signal in the activation of anti-tumor immune responses, holding marked promise in the field of tumor immunotherapy. However, low immunogenicity tumors pose challenges in achieving complete induction of ICD, thereby limiting the response rates of immunotherapy in clinical patients. The emergence of cuproptosis as a new form of regulated cell death has presented a promising strategy for enhanced immunotherapy of low immunogenic tumors. To trigger cuproptosis, copper-ionophore elesclomol (ES) had to be employed for the copper-transporting-mediated process. Herein, we proposed a copper(II)-based metal-organic framework nanoplatform (Cu-MOF) to facilitate a cooperative delivery of encapsulated ES and copper (ES-Cu-MOF) to induce cuproptosis burst and enhance ICD of fibrosarcoma. Our results showed that the ES-Cu-MOF nano-regulator could effectively release Cu2+ and ES in response to the intracellular environment, resulting in elevated mitochondrial ROS generation and initiated cuproptosis of tumor cells. Furthermore, sequential ICDs were significantly triggered via the ES-Cu-MOF nano-regulator to activate the anti-tumor immune response. The results of tumor inhibition experiment indicated that the nano-regulator of ES-Cu-MOF obviously accumulated in the tumor site, inducing ICD for dendritic cell activation. This enabled an increased infiltration of cytotoxic CD8+ T cells and consequently enhanced antitumor immune responses for successfully suppressing fibrosarcoma growth. Thus, the copper(II)-based metal-organic framework nano-regulator offered a promising approach for inducing cuproptosis and cuproptosis-stimulated ICD for cancer immunotherapy.

The lysosome-mitochondrion crosstalk engaged in silver nanoparticles-disturbed mitochondrial homeostasis.

Given their increasing industrial and biomedical applications, silver nanoparticles (AgNPs) have become widely present in the environment. However, to date, studies on their potential health risks have been far from sufficient, especially those regarding their neurotoxic effects. This study investigated the neurotoxic effects of AgNPs on neural PC-12 cells in the context of mitochondria, which play an important role in AgNP-induced cellular metabolism disturbance and even cell death. Our results show that the endocytosed AgNPs, and not extracellular Ag+, appear to directly determine cell fate. Importantly, endocytosed AgNPs led to mitochondrial swelling and vacuolation without direct interaction. Although mitophagy, a selective autophagy process, was invoked to rescue damaged mitochondria, it failed to function in mitochondrial degradation and recycling. Discovery of the underlying mechanism showed that the endocytosed AgNPs could directly translocate into lysosomes and then cause lysosome perturbation, which is the main factor leading to mitophagy blockade and the subsequent accumulation of defective mitochondria. After lysosomal reacidification via cyclic adenosine monophosphate (cAMP), AgNP-induced dysfunctional autolysosome formation and disturbed mitochondrial homeostasis were reversed. In summary, this study reveals that lysosome-mitochondrion crosstalk is a main mechanism for AgNP-induced neurotoxic effects, offering an inspiring perspective on the neurotoxic effects of AgNPs.

Epidemic monitoring in real-time based on dynamic grid search and Monte Carlo numerical simulation algorithm.

Building upon the foundational principles of the grid search algorithm and Monte Carlo numerical simulation, this article introduces an innovative epidemic monitoring and prevention plan. The plan offers the capability to accurately identify the sources of infectious diseases and predict the final scale and duration of the epidemic. The proposed plan is implemented in schools and society, utilizing computer simulation analysis. Through this analysis, the plan enables precise localization of infection sources for various demographic groups, with an error rate of less than 3%. Additionally, the plan allows for the estimation of the epidemic cycle duration, which typically spans around 14 days. Notably, higher population density enhances fault tolerance and prediction accuracy, resulting in smaller errors and more reliable simulation outcomes. Overall, this study provides highly valuable theoretical guidance for effective epidemic prevention and control efforts.

Entrectinib inhibits NLRP3 inflammasome and inflammatory diseases by directly targeting NEK7.

Excessive inflammation caused by abnormal activation of the NLRP3 inflammasome contributes to the pathogenesis of multiple human diseases, but clinical drugs targeting the NLRP3 inflammasome are still not available. In this study, we identify entrectinib (ENB), a US Food and Drug Administration (FDA)-approved anti-cancer agent, as a target inhibitor of the NLRP3 inflammasome to treat related diseases. ENB specifically blocks NLRP3 without affecting activation of other inflammasomes. Furthermore, we demonstrate that ENB directly binds to arginine 121 (R121) of NEK7 and blocks the interaction between NEK7 and NLRP3, thereby inhibiting inflammasome assembly and activation. In vivo studies show that ENB has a significant ameliorative effect on mouse models of NLRP3 inflammasome-related diseases, including lipopolysaccharide (LPS)-induced systemic inflammation, monosodium urate (MSU)-induced peritonitis, and high-fat diet (HFD)-induced type 2 diabetes (T2D). These data show that ENB is a targeted inhibitor of NEK7 with strong anti-NLRP3 inflammasome activity, making it a potential candidate drug for the treatment of inflammasome-related diseases.

A novel strategy for enhancing bioremediation of polychlorinated biphenyl-contaminated soil with resuscitation promoting factor and resuscitated strain.

PCBs bioremediation is largely impeded by the reduced metabolic activity and degradation ability of indigenous and exogenous microorganisms. Resuscitation promoting factor (Rpf) of Micrococcus luteus, has been reported to resuscitate and stimulate the growth of PCB-degrading bacterial populations, and the resuscitated strains exhibited excellent PCB-degrading performances. Therefore, this study was conducted to assess the feasibility of supplementing Rpf (SR) or resuscitated strain LS1 (SL), or both (SRL) for enhanced bioremediation of PCB-contaminated soil. The results indicated that Rpf and/or LS1 amended soil microcosms achieved more rapid PCBs degradation, which were 1.1-3.2 times faster than control microcosms. Although soil-inoculated LS1 maintained the PCB-degrading activity, higher PCBs degradation was observed in Rpf-amended soil microcosms compared with SL. The order of enhancement effect on PCBs bioremediation was SRL > SR > SL. PCBs degradation in soil microcosms was via HOPDA-benzoate-catechol/protocatechuate pathways. The improved PCBs degradation in Rpf-amended soil microcosms was attributed to the enhanced abundances of PCB-degrading populations which were mainly belonged to Proteobacteria and Actinobacteria. These results suggest that Rpf and resuscitated strains serve as effective additive and bio-inoculant for enhanced bioremediation, providing new approaches to realizing large scale applications of in situ bioremediation.