Ultrasound-Triggered Piezoelectric Catalysis of Zinc Oxide@Glucose Derived Carbon Spheres for the Treatment of MRSA Infected Osteomyelitis.

Currently, methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis is a clinically life-threatening disease, however, long-term antibiotic treatment can lead to bacterial resistance, posing a huge challenge to treatment and public health. In this study, glucose-derived carbon spheres loaded with zinc oxide (ZnO@HTCS) are successfully constructed. This composite demonstrates the robust ability to generate reactive oxygen species (ROS) under ultrasound (US) irradiation, eradicating 99.788% ± 0.087% of MRSA within 15 min and effectively treating MRSA-induced osteomyelitis infection. Piezoelectric force microscopy tests and finite element method simulations reveal that the ZnO@HTCS composite exhibits superior piezoelectric catalytic performance compared to pure ZnO, making it a unique piezoelectric sonosensitizer. Density functional theory calculations reveal that the formation of a Mott-Schottky heterojunction and an internal piezoelectric field within the interface accelerates the electron transfer and the separation of electron-hole pairs. Concurrently, surface vacancies of the composite enable the adsorption of a greater amount of oxygen, enhancing the piezoelectric catalytic effect and generating a substantial quantity of ROS. This work not only presents a promising approach for augmenting piezoelectric catalysis through construction of a Schottky heterojunction interface but also provides a novel, efficient therapeutic strategy for treating osteomyelitis.

A Smart Bacteria-Capture-Killing Vector for Effectively Treating Osteomyelitis Through Synergy Under Microwave Therapy.

Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.

Natural Extracts for Antibacterial Applications.

Bacteria-induced epidemics and infectious diseases are seriously threatening the health of people around the world. In addition, antibiotic therapy has been inducing increasingly more serious bacterial resistance, which makes it urgent to develop new treatment strategies to combat bacteria, including multidrug-resistant bacteria. Natural extracts displaying antibacterial activity and good biocompatibility have attracted much attention due to greater concerns about the safety of synthetic chemicals and emerging drug resistance. These antibacterial components can be isolated and utilized as antimicrobials, as well as transformed, combined, or wrapped with other substances by using modern assistive technologies to fight bacteria synergistically. This review summarizes recent advances in natural extracts from three kinds of sources-plants, animals, and microorganisms-for antibacterial applications. This work discusses the corresponding antibacterial mechanisms and the future development of natural extracts in antibacterial fields.

Electron Aggregation and Oxygen Fixation Reinforced Microwave Dynamic and Thermal Therapy for Effective Treatment of MRSA-Induced Osteomyelitis.

Antibiotics are frequently used to clinically treat osteomyelitis caused by bacterial infections. However, extended antibiotic use may result in drug resistance, which can be life threatening. Here, a heterojunction comprising Fe2O3/Fe3S4 magnetic composite is constructed to achieve short-term and efficient treat osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). The Fe2O3/Fe3S4 composite exhibits powerful microwave (MW) absorption properties, thereby effectively converting incident electromagnetic energy into thermal energy. Density functional theory calculations demonstrate that Fe2O3/Fe3S4 possesses significant charge accumulation and oxygen-fixing capacity at the heterogeneous interface, which provides more active sites and oxygen sources for trapping electromagnetic hotspots. The finite element analysis indicates that Fe2O3/Fe3S4 displays a larger electromagnetism field enhancement parameter than Fe2O3 owing to a significant increase in electromagnetic hotspots. These hotspots contribute to charge differential accumulation and depletion motions at the interface, thereby augmenting the release of free electrons that subsequently combine with the oxygen adsorbed by Fe2O3/Fe3S4 to generate reactive oxygen species (ROS) and heat. This research, which achieves extraordinary bacterial eradication through the synergistic effect of microwave thermal therapy (MWTT) and microwave dynamic therapy (MDT), presents a novel strategy for treating deep-tissue bacterial infections.

Etching of Ag nanoparticles triggered bidirectional regulation for electrochemiluminescence ratiometric immunoassay.

A highly efficient ratiometric electrochemiluminescence (ECL) immunoassay was explored by bidirectionally regulating the ECL intensity of two luminophors. The immunoassay was conducted in a split-type mode consisting of an ECL detection procedure and a sandwich immunoreaction. The ECL detection was executed using a dual-disk glassy carbon electrode modified with two potential-resolved luminophors (g-C3N4-Ag and Ru-MOF-Ag nanocomposites), and the sandwich immunoreaction using glucose oxidase (GOx)-modified SiO2 nanospheres as labels was carried out in a 96-well plate. The Ag nanoparticles (NPs) acted as bifunctional units both for triggering the resonance energy transfer (RET) with g-C3N4 and for accelerating the electron transfer rate of the Ru-MOF-Ag ECL reaction. When the H2O2 catalyzed by GOx in the 96-well plate was transferred to the dual-disk glass carbon electrode, the doped Ag NPs in the two luminophors could be etched, thus destroying the RET between C3N4 and the accelerated reaction to Ru-MOF, resulting in an opposite trend in the ECL signal outputted from the dual disks. Using the ratio of the two signals for quantification, the constructed immunosensor for a model target, i.e. myoglobin, exhibited a low detection limit of 4.7 × 10-14 g/mL. The ingenious combination of ECL ratiometry, bifunctional Ag NPs, and a split-type strategy effectively reduces environmental and human errors, offering a more precise and sensitive analysis for complex samples.

Floating on groundwater: Insight of multi-source remote sensing for Qaidam basin.

Situated in the north of the Qinghai-Tibet Plateau, the Qaidam Basin experiences limited precipitation and significant evaporation. Despite these conditions, it stands out as one of the most densely distributed lakes in China. The formation of these lakes is controversial: whether the lake water primarily originates from local precipitation or external water sources. To address this issue, this paper explores the recharge sources of lakes in the Qaidam Basin and the circulation patterns of groundwater from a remote sensing perspective. Based on deep learning networks, we optimized the soft object regions of the Object-Contextual Representations Network (OCRNet) and proposed the Remote·Sensing Adaptive-Improved OCRNet (RSA-IOCRNet). Compared with seven other networks, RSA-IOCRNet obtained better experimental results and was used to construct an area sequence of 16 major lakes in the Qaidam Basin. Combined with multi-source data, the comprehensive analysis indicates no significant correlation between climatic factors and lake changes, while an obvious correlation between lakes and groundwater changes in the eastern Qaidam, consisting with the results of the field survey. Deep-circulating groundwater recharges numerous Qaidam lakes through upwelling from fault zones, such as Gasikule Lake and Xiaochaidan Lake. Groundwater in the Qaidam Basin is more depleted in hydrogen-oxygen isotope characteristics than surface water in the basin, but similar to some river water in the endorheic Tibetan Plateau. This indicates that Tibetan seepage water, estimated at approximately 540 billion m3/a, is transported through the Qaidam Basin via deep circulation. Moreover, it rises to recharge the groundwater and lakes within this basin through fracture zones, extending to various arid and semi-arid regions such as Taitema Lake. This work provides a new perspective on the impact of deep groundwater on lakes and water circulation in these areas.

Ultrasound-Responsive Microneedles Eradicate Deep-Layered Wound Biofilm Based on TiO2 Crystal Phase Engineering.

Wound biofilm infection has an inherent resistance to antibiotics, requiring physical debridement combined with chemical reagents or antibiotics in clinical treatment, but it is invasive and may exist as incomplete debridement. So, a new type of noninvasive and efficient treatment is needed to address this problem. Here, the crystal phase engineering of TiO2 is presented to explore the sonocatalytic properties of TiO2 nanoparticles with different phases, and find that the anatase-brookite TiO2  (AB) has the best antibacterial efficiency of 99.94% against S. aureus under 15 min of ultrasound (US) irradiation. The type II homojunction of AB not only enhances the adsorption and decreases the activation energy of O2 , respectively, but also has a great interfacial charge transfer efficiency under US, which can produce more reactive oxygen species than other types of TiO2 . The microneedles (MN) penetrate the biofilm in wound tissue and quickly disperse the loaded AB into the biofilm because the ultrasonic cavitation accelerates the dissolution of microneedles, which non-invasively and efficiently eradicates the deep-layered biofilm under US. This work explores the relationship between the phase composition of TiO2 and sonocatalytic property for the first time, and provides a new treatment strategy for wound biofilm infection through US-assisted microneedles therapy.

Metal Ion Coordination Improves Graphite Nitride Carbon Microwave Therapy in Antibacterial and Osteomyelitis Treatment.

The ability to effectively treat deep bacterial infections while promoting osteogenesis is the biggest treatment demand for diseases such as osteomyelitis. Microwave therapy is widely studied due to its remarkable ability to penetrate deep tissue. This paper focuses on the development of a microwave-responsive system, namely, a zinc ion (Zn2+ ) doped graphite carbon nitride (CN) system (BZCN), achieved through two high-temperature burning processes. By subjecting composite materials to microwave irradiation, an impressive 99.81% eradication of Staphylococcus aureus is observed within 15 min. Moreover, this treatment enhances the growth of bone marrow stromal cells. The Zn2+ doping effectively alters the electronic structure of CN, resulting in the generation of a substantial number of free electrons on the material's surface. Under microwave stimulation, sodium ions collide and ionize with the free electrons generated by BZCN, generating a large amount of energy, which reacts with water and oxygen, producing reactive oxygen species. In addition, Zn2+ doping improves the conductivity of CN and increases the number of unsaturated electrons. Under microwave irradiation, polar molecules undergo movement and generate frictional heat. Finally, the released Zn2+ promotes macrophages to polarize toward the M2 phenotype, which is beneficial for tibial repair.

Engineering Dynamic Defect of CeIII /CeIV -Based Metal-Organic Framework through Ultrasound-Triggered Au Electron Trapper for Sonodynamic Therapy of Osteomyelitis.

Defect engineering is an important way to tune the catalytic properties of metal-organic framework (MOF), yet precise control of defects is difficult to achieve. Herein, a cerium-based MOF (CeTCPP) is decorated with Au nanoparticles. Under ultrasound irradiation, Au nanoparticles can precisely turn 1/3 of the pristine Ce3+ nodes into Ce4+ . With the stable existence of Ce4+ , the coordination of Ce nodes changed, causing the structural irregularity in CeTCPP-Au, so that the electron-hole recombination is obviously hindered, facilitating the generation of reactive oxygen species. Therefore, under 20 min of ultrasound irradiation, the CeTCPP-Au showed superior antibacterial efficacy of over 99% against Staphylococcus aureus and Escherichia coli with good biocompatibility, which is further used for effective therapy of osteomyelitis. Overall, this work provides a dynamic defect formation strategy of MOF through the electron trapping of Au nanoparticles, which also sheds light on sonodynamic therapy in curing deep-seated lesions.

Metal organic framework-based antibacterial agents and their underlying mechanisms.

Bacteria, as the most abundant living organisms, have always been a threat to human life until the development of antibiotics. However, with the wide use of antibiotics over a long time, bacteria have gradually gained tolerance to antibiotics, further aggravating threat to human beings and environmental safety significantly. In recent decades, new bacteria-killing methods based on metal ions, hyperthermia, free radicals, physical pricks, and the coordination of several multi-mechanisms have attracted increasing attention. Consequently, multiple types of new antibacterial agents have been developed. Among them, metal organic frameworks (MOFs) appear to play an increasingly important role. The unique characteristics of MOFs make them suitable multiple-functional platforms. By selecting the appropriate metastable coordination bonds, MOFs can act as reservoirs and release antibacterial metal ions or organic linkers; by constructing a porous structure, MOFs can act as carriers for multiple types of agents and achieve slow and sustained release; and by designing their composition and the pore structure precisely, MOFs can be endowed with properties to produce heat and free radicals under stimulation. Importantly, in combination with other materials, MOFs can act as a platform to kill bacteria effectively through the synergistic effect of multiple types of mechanisms. In this review, we focus on the recent development of MOF-based antibacterial agents, which are classified according to their antibacterial mechanisms.

Oxygen Vacancies-Rich Heterojunction of Ti3 C2 /BiOBr for Photo-Excited Antibacterial Textiles.

Pathogenic bacteria that adhere on the surface of textiles, especially healthcare workers' uniforms, have brought severe problems, including nosocomial infection and other infectious diseases. Here, antibacterial textiles are fabricated by in situ growing oxygen vacancies (OVs) BiOBr on the surface of Ti3 C2 nanosheets followed by in situ polymerization of polypyrrole (ppy). The formed Schottky heterojunction containing OVs of Ti3 C2 /BiOBr effectively enhance the transfer and separation of photogenerated carriers, inhibit the recombination, and decrease the band gap by introducing defect level, which significantly improve the photocatalytic activity, leading to higher reactive oxygen species (ROS) under light irradiation. Therefore, the antibacterial efficacy of textiles reaches up to 98.64% against Staphylococcus aureus and 99.89% against Escherichia coli with the assistance of hyperthermia under light irradiation for 15 min. This work provides insights for designing photo-excited antibacterial textiles by interfacial construction based on Schottky junctions and OVs in the incorporated nanomaterials.

Ultrasonic Interfacial Engineering of MoS2 -Modified Zn Single-Atom Catalysts for Efficient Osteomyelitis Sonodynamic Ion Therapy.

Osteomyelitis is considered as the most serious bone infection, which can lead to the bone destruction or fatal sepsis. Clinical treatments through frequent antibiotics administration and surgical debridement bring inevitable side effects including drug-resistance and disfigurements. It is urgent to develop an antibiotics-free and rapid strategy to treat osteomyelitis. Herein, a bifunctional sonosensitizer that consists of porphyrin-like Zn single-atom catalysts (g-ZnN4 ) and MoS2 quantum dots is developed, which exhibits excellent sonodynamic antibacterial efficiency and osteogenic ability. It is found that the construction of heterogeneous interfaces of g-ZnN4 -MoS2 fully activates the adsorbed O2 due to the increased interface charge transfer, enhanced spin-flip, and reduced activation energy of O2 . The generated 1 O2 can kill methicillin-resistant Staphylococcus aureus (MRSA) with an antibacterial efficiency of 99.58% under 20 min of ultrasound (US) irradiation. The Zn single atoms immobilized in g-ZnN4 can be released steadily in the form of Zn2+ for 28 days within safe concentration, realizing the great osteoinductive ability of such a sonosensitizer. For the treatment of MRSA-infected osteomyelitis, the inflammation and bone loss can be significantly suppressed through sonodynamic ion therapy. This work provides another strategy for developing high efficiency sonosensitizer through ultrasound interfacial engineering.

Magnetic Composite Rapidly Treats Staphylococcus aureus-Infected Osteomyelitis through Microwave Strengthened Thermal Effects and Reactive Oxygen Species.

It is difficult to effectively treat bacterial osteomyelitis using photothermal therapy or photodynamic therapy due to poor penetration of light. Here, a microwave (MW)-excited magnetic composite of molybdenum disulfide (MoS2 ) / iron oxide (Fe3 O4 ) is reported for the treatment of bacteria-infected osteomyelitis. In in vitro and in vivo experiments, MoS2 /Fe3 O4 is shown to effectively eradicate bacteria-infected mouse tibia osteomyelitis, due to MW thermal enhancement and reactive oxygen species (ROS) (1 O2 and ·O2 - ) production under MW radiation. In addition, the mechanism of MW heat generation is proposed by MW network vector analysis. By the density functional theory and finite element method, the ROS generation mechanism is proposed. The synergy or conductive network between dielectric MoS2 and magnetic Fe3 O4 can reach both enhancement of the dielectric and magnetic attenuation capability. In addition, abundant interfaces are generated to enhance the attenuation of electromagnetic waves by MoS2 and Fe3 O4, introducing multiple reflections and interfacial polarization. Therefore, MoS2 /Fe3 O4 has excellent MW absorption ability based on the synergy or conductive network between MoS2 and magnetic Fe3 O4 as well as multiple dielectric reflections and interfacial polarization.

Development of a powerful synthetic hybrid promoter to improve the cellulase system of Trichoderma reesei for efficient saccharification of corncob residues.

BACKGROUND: The filamentous fungus Trichoderma reesei is a widely used workhorse for cellulase production in industry due to its prominent secretion capacity of extracellular cellulolytic enzymes. However, some key components are not always sufficient in this cellulase cocktail, making the conversion of cellulose-based biomass costly on the industrial scale. Development of strong and efficient promoters would enable cellulase cocktail to be optimized for bioconversion of biomass. RESULTS: In this study, a synthetic hybrid promoter was constructed and applied to optimize the cellulolytic system of T. reesei for efficient saccharification towards corncob residues. Firstly, a series of 5' truncated promoters in different lengths were established based on the strong constitutive promoter Pcdna1. The strongest promoter amongst them was Pcdna1-3 (- 640 to - 1 bp upstream of the translation initiation codon ATG), exhibiting a 1.4-fold higher activity than that of the native cdna1 promoter. Meanwhile, the activation region (- 821 to - 622 bp upstream of the translation initiation codon ATG and devoid of the Cre1-binding sites) of the strong inducible promoter Pcbh1 was cloned and identified to be an amplifier in initiating gene expression. Finally, this activation region was fused to the strongest promoter Pcdna1-3, generating the novel synthetic hybrid promoter Pcc. This engineered promoter Pcc drove strong gene expression by displaying 1.6- and 1.8-fold stronger fluorescence intensity than Pcbh1 and Pcdna1 under the inducible condition using egfp as the reporter gene, respectively. Furthermore, Pcc was applied to overexpress the Aspergillus niger ß-glucosidase BGLA coding gene bglA and the native endoglucanase EG2 coding gene eg2, achieving 43.5-fold BGL activity and 1.2-fold EG activity increase, respectively. Ultimately, to overcome the defects of the native cellulase system in T. reesei, the bglA and eg2 were co-overexpressed under the control of Pcc promoter. The bglA-eg2 double expression strain QPEB70 exhibited a 178% increase in total cellulase activity, whose cellulase system displayed 2.3- and 2.4-fold higher saccharification efficiency towards acid-pretreated and delignified corncob residues than the parental strain, respectively. CONCLUSIONS: The synthetic hybrid promoter Pcc was generated and employed to improve the cellulase system of T. reesei by expressing specific components. Therefore, construction of synthetic hybrid promoters would allow particular cellulase genes to be expressed at desired levels, which is a viable strategy to optimize the cellulolytic enzyme system for efficient biomass bioconversion.

H2O2-activated independently bidirectional regulation for a sensitive and accurate electrochemiluminescence ratiometric analysis.

Potential-resolved electrochemiluminescence (ECL) ratiometric analysis has become a research hotspot in bioassays by virtue of its good accuracy, versatility and specificity. Current ECL ratiometry mainly focuses on the competition for the co-reactant or quantitative analysis using a variable signal and a changeless signal; the disorganized change or small difference between the two signals may affect the accuracy and sensitivity of detection. In this study, we have developed a novel ECL ratiometric sensor based on the bidirectional regulation of two independent co-reaction systems by H2O2. H2O2 as a bidirectional moderator permits the ECL signals of the cathode and anode to independently change in opposite trends, which greatly enhances the organization and difference between the two signals. The ratio of the two signals is used to realize the quantitative analysis of myoglobin (MyO) with a good linear relationship between log(ECLcathode/ECLanode) and log CMyO in the range of 1.0 × 10-13 to 1.0 × 10-7 g mL-1. The detection limit is 4.0 × 10-14 g mL-1. Furthermore, it showed excellent performance in the determination of MyO in human serum samples. The proposed biosensor provides some developments for the sensitive and accurate detection of disease markers.

Composition tunability of semiconductor radiosensitizers for low-dose X-ray induced photodynamic therapy.

Radiation therapy is one of the most commonly used methods in clinical cancer treatment, and radiosensitizers could achieve enhanced therapeutic efficacy by incorporating heavy elements into structures. However, the secondary excitation of these high-Z elements-doped nanosensitizers still imply intrinsic defects of low efficiency. Herein, we designed Bi-doped titanium dioxide nanosensitizers in which high-Z Bi ions with adjustable valence state (Bi3+ or Bi4+) replaced some positions of Ti4+ of anatase TiO2, increasing both X-rays absorption and oxygen vacancies. The as-prepared TiO2:Bi nanosensitizers indicated high ionizing radiation energy-transfer efficiency and photocatalytic activity, resulting in efficient electron-hole pair separation and reactive oxygen species production. After further modification with cancer cell targeting peptide, the obtained nanoplatform demonstrated good performance in U87MG cell uptakes and intracellular radicals-generation, severely damaging the vital subcellular organs of U87MG cells, such as mitochondrion, membrane lipid, and nuclei etc. These combined therapeutic actions mediated by the composition-tunable nanosensitizers significantly inhibited the U87MG tumor growth, providing a refreshing strategy for X-ray induced dynamic therapy of malignant tumors.

The recent progress on metal-organic frameworks for phototherapy.

Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over the world. The commonly used antibiotic therapy cannot effectively treat these diseases within a short time, and also bring about adverse effects such as drug resistance and immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to treat these diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) or induce a temperature increase, which leads to the death of targeted cells. These two kinds of killing strategies are referred to as photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. So far, many photo-responsive agents have been developed. Among them, the metal-organic framework (MOF) is becoming one of the most promising photo-responsive materials because its structure and chemical compositions can be easily modulated to achieve specific functions. MOFs can have intrinsic photodynamic or photothermal ability under the rational design of MOF construction, or serve as the carrier of therapeutic agents, owing to its tunable porosity. MOFs also provide feasibility for various combined therapies and targeting methods, which improves the efficiency of phototherapy. In this review, we firstly investigated the principles of phototherapy, and comprehensively summarized recent advances of MOF in PDT, PTT and synergistic therapy, from construction to modification. We expect that our demonstration will shed light on the future development of this field, and bring it one step closer to clinical trials.

2D MOF Periodontitis Photodynamic Ion Therapy.

Traditional surgical intervention and antibiotic treatment are poor and even invalid for chronic diseases including periodontitis induced by diverse oral pathogens, which often causes progressive destruction of tissues, even tooth loss, and systemic diseases. Herein, an ointment comprising atomic-layer Fe2O3-modified two-dimensional porphyrinic metal-organic framework (2D MOF) nanosheets is designed by incorporating a polyethylene glycol matrix. After the atomic layer deposition surface engineering, the enhanced photocatalytic activity of the 2D MOF heterointerface results from lower adsorption energy and more charge transfer amounts due to the synergistic effect of metal-linker bridging units, abundant active sites, and an excellent light-harvesting network. This biocompatible and biodegradable 2D MOF-based heterostructure exhibits broad-spectrum antimicrobial activity (99.87 ± 0.09%, 99.57 ± 0.21%, and 99.03 ± 0.24%) against diverse oral pathogens (Porphyromonas gingivalis, Fusobacterium nucleatum, and Staphylococcus aureus) by the synergistic effect of reactive oxygen species and released ions. This photodynamic ion therapy exhibits a superior therapeutic effect to the reported clinical periodontitis treatment owing to rapid antibacterial activity, alleviative inflammation, and improved angiogenesis.

The substrate-dependent regulatory effects of the AfeI/R system in Acidithiobacillus ferrooxidans reveals the novel regulation strategy of quorum sensing in acidophiles.

A LuxI/R-like quorum sensing (QS) system (AfeI/R) has been reported in the acidophilic and chemoautotrophic Acidithiobacillus spp. However, the function of AfeI/R remains unclear because of the difficulties in the genetic manipulation of these bacteria. Here, we constructed different afeI mutants of the sulfur- and iron-oxidizer A. ferrooxidans, identified the N-acyl homoserine lactones (acyl-HSLs) synthesized by AfeI, and determined the regulatory effects of AfeI/R on genes expression, extracellular polymeric substance synthesis, energy metabolism, cell growth and population density of A. ferrooxidans in different energy substrates. Acyl-HSLs-mediated distinct regulation strategies were employed to influence bacterial metabolism and cell growth of A. ferrooxidans cultivated in either sulfur or ferrous iron. Based on these findings, an energy-substrate-dependent regulation mode of AfeI/R in A. ferrooxidans was illuminated that AfeI/R could produce different types of acyl-HSLs and employ specific acyl-HSLs to regulate specific genes in response to different energy substrates. The discovery of the AfeI/R-mediated substrate-dependent regulatory mode expands our knowledge on the function of QS system in the chemoautotrophic sulfur- and ferrous iron-oxidizing bacteria, and provides new insights in understanding energy metabolism modulation, population control, bacteria-driven bioleaching process, and the coevolution between the acidophiles and their acidic habitats.

Development and clinical validation of a novel 9-gene prognostic model based on multi-omics in pancreatic adenocarcinoma.

The prognoses of patients with pancreatic adenocarcinoma (PAAD) remain poor due to the lack of biomarkers for early diagnosis and effective prognosis prediction. RNA sequencing, single nucleotide polymorphism, and copy number variation data were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to identify prognosis-related genes. GISTIC 2.0 was used to identify significantly amplified or deleted genes, and Mutsig 2.0 was used to analyze the mutation data. The Lasso method was used to construct a risk prediction model. The Rms package was used to evaluate the overall predictive performance of the signature. Finally, Western blot and polymerase chain reaction were performed to evaluate gene expression. A total of 54 candidate genes were obtained after integrating the genomic mutated genes and prognosis-related genes. The Lasso method was used to ascertain 9 characteristic genes, including UNC13B, TSPYL4, MICAL1, KLHDC7B, KLHL32, AIM1, ARHGAP18, DCBLD1, and CACNA2D4. The 9-gene signature model was able to help stratify samples at risk in the training and external validation cohorts. In addition, the overall predictive performance of our model was found to be superior to that of other models. KLHDC7B, AIM1, DCBLD1, TSPYL4, and MICAL1 were significantly highly expressed in tumor tissues compared to normal tissues. ARHGAP18 and CACNA2D4 had no difference in expression between tumor and normal tissues. UNC13B and KLHL32 expression in the normal group was higher than in the tumor group. The 9-gene signature constructed in this study can be used as a novel prognostic marker to predict the survival of patients with pancreatic adenocarcinoma.