Invasive Fusarium solani infection diagnosed by traditional microbial detection methods and metagenomic next-generation sequencing in a pediatric patient: a case report and literature review.

Fusarium solani, as an opportunistic pathogen, can infect individuals with immunosuppression, neutropenia, hematopoietic stem cell transplantation (HSCT), or other high-risk factors, leading to invasive or localized infections. Particularly in patients following allogeneic HSCT, Fusarium solani is more likely to cause invasive or disseminated infections. This study focuses on a pediatric patient who underwent HSCT for severe aplastic anemia. Although initial blood cultures were negative, an abnormality was detected in the 1,3-ß-D-glucan test (G test) post-transplantation. To determine the causative agent, blood samples were subjected to metagenomic next-generation sequencing (mNGS) and blood cultures simultaneously. Surprisingly, the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and mNGS differed slightly, with mNGS identifying Nectria haematonectria, while MALDI-TOF MS based on culture showed Fusarium solani. To clarify the results, Sanger sequencing was performed for further detection, and the results were consistent with those of MALDI-TOF MS. Since the accuracy of Sanger sequencing is higher than that of mNGS, the diagnosis was revised to invasive Fusarium solani infection. With advancements in technology, various detection methods for invasive fungi have been developed in recent years, such as mNGS, which has high sensitivity. While traditional methods may be time-consuming, they are important due to their high specificity. Therefore, in clinical practice, it is essential to utilize both traditional and novel detection methods in a complementary manner to enhance the diagnosis of invasive fungal infections.

Integrating Molecular Biology and Network Pharmacology to Analyze the Antidepressant Mechanism of Glycyrrhizaglabra.

INTRODUCTION: Antidepressants have adverse effects and induce drug resistance when used excessively or frequently. Therefore, adjuvants are needed to reduce the use of antidepressants during treatment. Traditional Chinese medicine (TCM) is an important adjunctive approach to depression with safety, environmental protection, and low toxicity. Glycyrrhizaglabra (licorice, GG) is a plant commonly used in various herbal remedies. METHOD: We investigated the antidepressant activity of GG, its active constituents, and potential depression-related targets. We combined animal behavioral and molecular biological assays with network pharmacology to analyze the antidepressant mechanism of GG. GG extracts reversed lipopolysaccharide (LPS)-induced depression-like behavior in behavioral tests. We selected 56 active compounds and 695 target compounds of licorice from TCMSP. The PPI network screened 80 core targets for enrichment analysis. It shows that GG significantly affected neurodegeneration pathways, neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, dopaminergic synapse, and MAPK signaling pathway. RESULT: Mechanistic studies showed that GG reduced IL-1ß, IL-6, and TNF-α levels, 5-HTRA1 expression, and GSK3ß phosphorylation in mouse hippocampus. It also increased BDNF and DRD1 expression and CREB and ERK1/2 phosphorylation. CONCLUSION: It shows that GG acted on these proteins to affect multiple pathways that mediate the pathogenesis of depression.

Single-atom Zr embedded Ti4O7 anode coupling with hierarchical CuFe2O4 particle electrodes toward efficient electrooxidation of actual pharmaceutical wastewater.

Electrocatalytic oxidation is commonly restricted by low degradation efficiency, slow mass transfer, and high energy consumption. Herein, a synergetic electrocatalysis system was developed for removal of various drugs, i.e., atenolol, florfenicol, and diclofenac sodium, as well as actual pharmaceutical wastewater, where the newly-designed single-atom Zr embedded Ti4O7 (Zr/Ti4O7) and hierarchical CuFe2O4 (CFO) microspheres were used as anode and microelectrodes, respectively. In the optimal reaction system, the degradation efficiencies of 40 mg L-1 atenolol, florfenicol, and diclofenac sodium could achieve up to 98.8%, 93.4%, and 85.5% in 120 min with 0.1 g L-1 CFO at current density of 25 mA cm-2. More importantly, in the flow-through reactor, the electrooxidation lasting for 150 min could reduce the COD of actual pharmaceutical wastewater from 432 to 88.6 mg L-1, with a lower energy consumption (25.67 kWh/m3). Meanwhile, the electrooxidation system maintained superior stability and environmental adaptability. DFT theory calculations revealed that the excellent performance of this electrooxidation system could be ascribed to the striking features of the reduced reaction energy barrier by single-atom Zr loading and abundant oxygen vacancies on the Zr/Ti4O7 surface. Moreover, the characterization and experimental results demonstrated that the CFO unique hierarchical structure and synergistic effect between electrodes were also the important factors that could improve the system performance. The findings shed light on the single-atom material design for boosting electrochemical oxidation performance.

Antifungal Mechanism of Phenazine-1-Carboxylic Acid against Pestalotiopsis kenyana.

Pestalotiopsis sp. is an important class of plant pathogenic fungi that can infect a variety of crops. We have proved the pathogenicity of P. kenyana on bayberry leaves and caused bayberry blight. Phenazine-1-carboxylic acid (PCA) has the characteristics of high efficiency, low toxicity, and environmental friendliness, which can prevent fungal diseases on a variety of crops. In this study, the effect of PCA on the morphological, physiological, and molecular characteristics of P. kenyana has been investigated, and the potential antifungal mechanism of PCA against P. kenyana was also explored. We applied PCA on P. kenyana in vitro and in vivo to determine its inhibitory effect on PCA. It was found that PCA was highly efficient against P. kenyana, with EC50 around 2.32 µg/mL, and the in vivo effect was 57% at 14 µg/mL. The mechanism of PCA was preliminarily explored by transcriptomics technology. The results showed that after the treatment of PCA, 3613 differential genes were found, focusing on redox processes and various metabolic pathways. In addition, it can also cause mycelial development malformation, damage cell membranes, reduce mitochondrial membrane potential, and increase ROS levels. This result expanded the potential agricultural application of PCA and revealed the possible mechanism against P. kenyana.

An infection-microenvironment-targeted and responsive peptide-drug nanosystem for sepsis emergency by suppressing infection and inflammation.

Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation. Nevertheless, current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens. Omiganan, an antimicrobial peptide, has shown promise for neutralizing endotoxins and eliminating diverse pathogens. However, its clinical application is hindered by safety and stability concerns. Herein, we present a nanoscale drug delivery system (Omi-hyd-Dex@HA NPs) that selectively targets infectious microenvironments (IMEs) and responds to specific stimuli for efficient intervention in sepsis. The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid (HA). The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes, but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase. The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation. In multiple tissue infection and sepsis animal models, Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction, thereby preventing subsequent fatal complications and significantly improving survival outcomes. The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.

Molecular mechanisms of platinum­based chemotherapy resistance in ovarian cancer (Review).

Cisplatin is one of the most effective chemotherapy drugs for ovarian cancer, but resistance is common. The initial response to platinum­based chemotherapy is as high as 80%, but in most advanced patients, final relapse and death are caused by acquired drug resistance. The development of resistance to therapy in ovarian cancer is a significant hindrance to therapeutic efficacy. The resistance of ovarian cancer cells to chemotherapeutic mechanisms is rather complex and includes multidrug resistance, DNA damage repair, cell metabolism, oxidative stress, cell cycle regulation, cancer stem cells, immunity, apoptotic pathways, autophagy and abnormal signaling pathways. The present review provided an update of recent developments in our understanding of the mechanisms of ovarian cancer platinum­based chemotherapy resistance, discussed current and emerging approaches for targeting these patients and presented challenges associated with these approaches, with a focus on development and overcoming resistance.

Investigation on the improvement of activated sludge dewaterability using different iron forms (ZVI vs. Fe(II))/peroxydisulfate combined vertical electro-dewatering processes.

The high moisture content (MC) of activated sludge dewatered by traditional vertical electro-dewatering (VED) is unable to meet the disposal requirements. Therefore, different iron forms (ZVI vs. Fe(II))/peroxydisulfate (PDS) combined VED (ZVI/PDS-VED and Fe(II)/PDS-VED) were employed to enhance the dewaterability of activated sludge. The dewatering behaviors of the two combined dewatering processes and the underlying mechanism related to the sludge characteristics were investigated and compared. Sludge was conditioned using ZVI/PDS and Fe(II)/PDS, respectively, and then dewatered by the VED in the experiment. Experimental results showed that with 0.3 g (g dry solids (DS))-1 of iron activators, 0.583 g (g DS) -1 of PDS, and 30 V of voltage, the MC of sludge after ZVI/PDS-VED and Fe(II)/PDS-VED reached the minimum values of 50.6 ± 1.2% and 32.1 ± 1.5%, respectively. ZVI/PDS and Fe(II)/PDS conditioning reduced the MC difference of sludge between the anode and the cathode during the VED, facilitating the water homogenization in the sludge cake. ZVI/PDS-VED and Fe(II)/PDS-VED could effectively reduce the bound water and the free water. Free water had high correlations with α-helix (r = 0.999, p < 0.05) and CO (r = 0.998, p < 0.05). Compared with the traditional VED and the ZVI/PDS-VED, the Fe(II)/PDS-VED had a greater improvement of sludge dewaterability due to the more efficient degradation of extracellular polymeric substances and the increase of sludge surface hydrophobicity. This study promoted the development of the new sludge deep-dewatering technology.

The first case of Ochrobactrum intermedium bacteremia in a pediatric patient with malignant tumor.

BACKGROUND: Ochrobactrum spp. are non-fermenting, Gram-negative bacilli that are regarded as emerging human pathogens of low virulence that can cause infections. The first identified case of Ochrobactrum intermedium was reported in 1998 in a liver transplantation patient with liver abcess. There are no reports of infections in pediatric patients. Here, we report the first case of O. intermedium bacteremia in a pediatric patient. CASE PRESENTATION: A two and a half years old male was admitted with fever, chills and nausea. He had been diagnosed as pineoblastoma and underwent surgical resection and chemotherapy. O. intermedium was isolated from his blood cultures and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), however, the Vitek II automated system failed to identify the organism. Then the pathogen was confirmed by 16S rDNA sequencing and average nucleotide identity result (ANI) confirmed the precise identification of O. intermedium at genomic level. In addition, the patient recovered well after antibiotic combined therapy. CONCLUSIONS: This, to our knowledge, is the first case of O. intermedium bacteremia in a pediatric patient with malignant tumor. Traditional biochemical identification methods such as API 20NE or VITEK2 system cannot differentiate O. anthropi and O. intermedium. MALDI-TOF may be a promising tool for rapid identification of microorganisms such as O. intermedium.

Tumor-targeting pH/redox dual-responsive nanosystem epigenetically reverses cancer drug resistance by co-delivering doxorubicin and GCN5 siRNA.

Multidrug resistance (MDR) is a major cause accounting for chemotherapy failure and recurrence of malignant tumors. A prominent mechanism underlying MDR is overexpression of P-glycoprotein (P-gp, a drug efflux pump). Promoting drug delivery efficacy by targeting tumor and concurrently suppressing drug efflux through down-regulating P-gp emerges as an effective strategy to enhance intracellular drug accumulation for combating MDR tumor. General Control Non-repressed 5 (GCN5), a histone acetyltransferase acting as an epigenetic regulator of multidrug resistance protein 1 (MDR1), positively regulates P-gp levels in drug-resistant cancer cells. Herein, a hyaluronic acid-coated, pH/redox dual-responsive nanosystem (HPMSNs) is fabricated for co-delivering doxorubicin (DOX) and GCN5 siRNA (siGCN5). This nanosystem can effectively encapsulate DOX and siRNA preventing premature leakage and releasing these therapeutics intracellularly via its pH/redox dual responsiveness. Through CD44-mediated targeting, DOX/siGCN5@HPMSNs increases drug internalization in CD44-overexpressing cancer cells, and markedly promotes DOX retention by down-regulating P-gp expression in drug-resistant cancers through silencing GCN5. Of note, in an MDR breast tumor model, DOX and siGCN5 co-delivered HPMSNs inhibits MDR tumor growth by 77%, abolishes P-gp-mediated drug resistance, and eliminates DOX's systemic toxicity. Thus, the tumor-targeting, stimuli-responsive nanosystem is an effective carrier for co-delivering anticancer drug and siRNA for combating cancer drug resistance. STATEMENT OF SIGNIFICANCE: We designed a tumor-targeting, pH/redox dual-responsive nanosystem (HPMSNs) for chemo-drug and siRNA co-delivery. This nanosystem efficiently co-delivered DOX and siGCN5 into drug-resistant cancer cells and significantly inhibited the tumor growth through: (1) HA shell enhanced the cellular internalization of loaded DOX and siGCN5 via CD44-mediated targeting; (2) the pH/redox dual-responsive nanosystem released the cargos in response to the intracellular environment; (3) the released siGCN5 downregulated P-gp epigenetically. In an MDR breast tumor model (MCF7/ADR), DOX and siGCN5 loaded HPMSNs markedly inhibited tumor growth, almost completely abolished P-gp expression, and minimized systemic toxicity of DOX.

Effects of sludge characteristics on electrical resistance and energy consumption during electro-dewatering process.

The increase of electrical resistance (ER) and energy consumption (EC) during the later stage of dewatering is a major problem hindering the development of electro-dewatering (EDW) technology. As the variations of sludge characteristics are significant during the EDW process, the relationships between sludge characteristics and ER and EC during EDW remain unclear. In this study, the effects of moisture content (MC), thickness, pH, conductivity, zeta potential, temperature, and gas volume on the ER and EC during the EDW process were statistically investigated using correlation and multiple linear regression analyses. Herein, the results showed that the ER of the sludge near the anode was primarily affected by pH, whereas the sludge near the cathode was primarily affected by the MC and conductivity. Further, sludge temperature and conductivity were the most reliable indicators to predict the EC near the anode and cathode, respectively. The results of this study provide theoretical guidance useful for solving the increase of ER and EC during the later stage of the EDW process.

Study of the variations in apparent electrical resistivity of activated sludge during the electro-dewatering process.

The high energy consumption of high apparent electrical resistivity (AER) in sludge during the later stages of the electro-dewatering (EDW) process is a difficult problem; however, analysis of sludge AER may contribute to a reduction in energy consumption. In this study, the variations in the AER of activated sludge and potential mechanisms related to sludge properties were systematically examined. First, a sludge cake was divided into four horizontal layers, in order to investigate the sludge AER in each layer. Then, the effects of variations in water distribution, oxidation-reduction potential (ORP), pH, metal ions, sludge conductivity, zeta potential, temperature, and sludge microstructure on the AER in each layer were explored. The results showed that the sludge AER began to increase from the bottom layers to the top layers when the moisture content (MC) was decreased to 60%. The formation of nonionic chemical systems and the gas barrier layer could increase the AER in the top layers, and the increase in sludge AER in the bottom layers was due to the decrease in MC and sludge conductivity. In addition, electrolyte release and electromigration had a significant effect on the sludge AER. This work identifies potential causes for the increase in AER, and provides a reference for solving problems related to high AER in sludge during the later stages of the EDW process.

The preparation of black titanium oxide nanoarray via coking fluorinated wastewater and application on coking wastewater treatment.

Coking wastewater is extremely toxic with poor biodegradability owing to the presence of refractory organics. Black titanium oxide nanotube array (BTN), not only photocatalyst but also electrocatalyst, is with definite potentiality in organic wastewater treatment. Here, we firstly developed an electrochemical method, using fluorinated coking wastewater as electrolyte rather than traditional fluorinated ethylene glycol, to prepare titanium oxide nanoarray economically. Unexpectedly, suspended pollutants and ammonia nitrogen in coking wastewater were removed in BTN preparation. Moreover, the as-prepared BTN could be further employed as photocatalyst or electrocatalyst to degrade dissolved organic matter in coking wastewater. As an electrocatalyst, BTN possessed the comparable •OH production activity about 9.9 × 10-15 M S-1 to boron-doped diamond, high oxygen evolution potential around 2.75 V, and high selectivity of chlorine production. Moreover, the biodegradability of treated coking wastewater could be effectively improved by using BTN as electrocatalyst in electrochemical oxidation, and the BOD/COD was from 0.19 to above 0.3 in 4 h at current density of 2 mA cm-2. The energy consumption was about 63-68 kWh kgCOD-1, lower than that of various reported electrodes. This study provided an economical and environmentally friendly method to prepare BTN, which was with positive application prospect in the field of coking wastewater treatment.

A Sequentially Responsive Nanosystem Breaches Cascaded Bio-barriers and Suppresses P-Glycoprotein Function for Reversing Cancer Drug Resistance.

Cancer chemotherapy is challenged by multidrug resistance (MDR) mainly attributed to overexpressed transmembrane efflux pump P-glycoprotein (P-gp) in cancer cells. Improving drug delivery efficacy while co-delivering P-gp inhibitors to suppress drug efflux is an often-used nanostrategy for combating MDR, which is however challenged by cascaded bio-barriers en route to cancer cells and P-gp inhibitors' adverse effects. To effectively breach the cascaded bio-barriers while avoiding P-gp inhibitors' adverse effects, a stealthy, sequentially responsive doxorubicin (DOX) delivery nanosystem (RCMSNs) is fabricated, composed of an extracellular-tumor-acidity-responsive polymer shell (PEG-b-PLLDA), pH/redox dual-responsive mesoporous silica nanoparticle-based carriers (MSNs-SS-Py), and cationic ß-cyclodextrin-PEI (CD-PEI) gatekeepers. The PEG-b-PLLDA corona makes RCMSNs stealthy with prolonged blood circulation time. Once tumors are reached, extracellular acidity degrades PEG-b-PLLDA, reversing nanosystem's surface charges to be positive, which drastically improves RCMSNs' tumor accumulation, penetration, and cellular internalization. Within cancer cells, CD-PEI gatekeepers detach to allow DOX unloading in response to intracellular acidity and glutathione and functionally act as a P-gp inhibitor, dampening P-gp's efflux activity by impairing ATP production. Thus, the resultant high-efficacy drug delivery along with reduced P-gp function cooperatively reverses MDR in vitro. Importantly, in preclinical tumor models, DOX@RCMSNs potently suppress MDR tumor growth without eliciting systemic toxicity, demonstrating their potential of clinical translation.

Investigation on the variations of sludge water holding capacity of electro-dewatering process.

Since the effect of electro-dewatering (EDW) on sludge water holding capacity was unknown, tests were conducted in this study to investigate the water holding capacity of EDW sludge and the potential mechanism related to the sludge physicochemical characteristics, EPS properties and sludge structure. Sludge was dewatered to the average moisture content (AMC) of 80%, 70% and 60% with different applied voltages at 20, 30 and 40V in EDW, respectively. Then the dewatered sludge near the anode and cathode were rewatered. The variation of sludge water holding capacity in EDW process was evaluated in terms of filterability and saturated moisture content (SMC), and the filterability was assessed by the specific resistance to filtration (SRF) of rewatered sludge. The results indicated that SRF of rewatered sludge near the cathode increased greatly. The proteins/polysaccharides (PN/PS) of loosely bound extracellular polymeric substances (LB-EPS) was significantly positively correlated with SRF (r = 0.891, p < 0.01). Moreover, the exposure of hydrophobic sites or groups in PN near the cathode improved the surface hydrophobicity of sludge, which reduced the filterability. In addition, higher voltage could destroy the sludge structure near the anode at the later stage of EDW process, leading to the decrease of SRF and SMC. These results expanded the knowledge about changes in sludge properties and water holding capacity during EDW process.

Redox-Responsive Dual Drug Delivery Nanosystem Suppresses Cancer Repopulation by Abrogating Doxorubicin-Promoted Cancer Stemness, Metastasis, and Drug Resistance.

Chemotherapy is a major therapeutic option for cancer patients. However, its effectiveness is challenged by chemodrugs' intrinsic pathological interactions with residual cancer cells. While inducing cancer cell death, chemodrugs enhance cancer stemness, invasiveness, and drug resistance of remaining cancer cells through upregulating cyclooxygenase-2/prostaglandin-E2 (COX-2/PGE2) signaling, therefore facilitating cancer repopulation and relapse. Toward tumor eradication, it is necessary to improve chemotherapy by abrogating these chemotherapy-induced effects. Herein, redox-responsive, celecoxib-modified mesoporous silica nanoparticles with poly(ß-cyclodextrin) wrapping (MSCPs) for sealing doxorubicin (DOX) are synthesized. Celecoxib, an FDA-approved COX-2 inhibitor, is employed as a structural and functional element to confer MSCPs with redox-responsiveness and COX-2/PGE2 inhibitory activity. MSCPs efficiently codeliver DOX and celecoxib into the tumor location, minimizing systemic toxicity. Importantly, through blocking chemotherapy-activated COX-2/PGE2 signaling, MSCPs drastically enhance DOX's antitumor activity by suppressing enhancement of cancer stemness and invasiveness as well as drug resistance induced by DOX-based chemotherapy in vitro. This is also remarkably achieved in three preclinical tumor models in vivo. DOX-loaded MSCPs effectively inhibit tumor repopulation by blocking COX-2/PGE2 signaling, which eliminates DOX-induced expansion of cancer stem-like cells, distant metastasis, and acquired drug resistance. Thus, this drug delivery nanosystem is capable of effectively suppressing tumor repopulation and has potential clinical translational value.

Invasive Fungal Infection Caused by Geotrichum clavatum in a Child with Acute Leukemia: First Documented Case from Mainland China.

Invasive fungal infections are one of the vital complications among acute leukemia patients undergoing induction chemotherapy. Among them, Geotrichum clavatum infections present extremely rarely with atypical clinical symptoms which make them difficult to diagnose. In this paper, we report a case of infection caused by Geotrichum clavatum in a 10-year old child with acute leukemia, which is the first documented case from mainland China. With underlying childhood leukemia, the child suffered from recurrent bacterial and fungal infection and even underwent abdominal surgery during the treatment. Fortunately, the therapeutic effect was finally achieved by adjusting the treatment program to dual anti-fungal treatment with micafungin and amphotericin B. Information regarding the epidemiological, clinical, and therapeutic features, in this case, shows significant perspectives for anti-fungal treatment for immunocompromised individuals, wherefore the rate of recovery and survival can be achieved.

Microbial community evolution and fate of antibiotic resistance genes along six different full-scale municipal wastewater treatment processes.

The evolution of microbial community and the fate of ARGs along different full-scale wastewater treatment processes (i.e., Anaerobic-Anoxic-Oxic, Oxidation Ditch, and Cyclic Activated Sludge System) were investigated in this study. We found that the sludges of bioreactors treating similar influent showed the similar microbial communities, independent of the treatment technologies. The horizontal gene transfer (HGT) mainly occurred in aeration tank rather that anaerobic/anoxic tank. More co-occurrence of potential pathogens and ARGs was found in wastewater than in sludge. Microbial biomass was the key driver for the fate of ARGs in wastewater, while mobile genetic elements (MGEs) was the key factor for the fate of ARGs in sludge. Combination of wastewater characteristics, microbial diversity, microbial biomass, and MGEs contributed to the variation of ARGs. Finally, it was found that enhanced nutrients removal process and tertiary treatment would benefit ARGs removal.

Electro-dewatering pretreatment of sludge to improve the bio-drying process.

In this study, the feasibility of electro-dewatering (EDW) as a pretreatment of the subsequent bio-drying process (EB process) was investigated from the point of view of the influence of EDW on the microbial biodegradability of sludge. The results showed that suitable EDW pretreatment was beneficial for microbial growth in the sludge cake, and in the subsequent bio-drying process it increased the metabolic activity of microorganisms. However, electric field strength impacted microbial activity and soluble chemical oxygen demand (SCOD) of the sludge. As the applied electric field strength increased from 20 to 60 V cm-1, the microbial activity of sludge decreased gradually but SCOD of sludge increased. The specific oxygen uptake rate (SOUR) at electric field strength of 20 V cm-1 was 8.7% higher than that of raw sludge. EDW pretreatment accelerated the drying rate of bio-drying process, and the final water content of sludge (44%) was 6.3% lower than that of non-pretreated sludge. It was observed that in the bio-drying process with an EDW pretreatment, the first peak temperature of the sludge pile was 58.7 °C at 36 h and the second peak temperature was 48.7 °C at 56 h, whereas that of the non-pretreated sludge was only 46.5 °C at 42 h and 40.3 °C at 62 h, respectively. The EDW sludge incorporating straw as a bulking agent showed promising results during bio-drying. In addition, EDW pretreatment of sludge to improve the bio-drying process showed lower energy consumption and cost.

Supramolecular Modular Approach toward Conveniently Constructing and Multifunctioning a pH/Redox Dual-Responsive Drug Delivery Nanoplatform for Improved Cancer Chemotherapy.

Because heterogeneity affects many functional aspects of a tumor, a way to overcome it is to arm nanosized drug delivery systems (nanoDDS) with diverse functions required to shatter heterogeneity. However, it remains technically challenging to fabricate a nanocarrier possessing all required functions. Here, we propose a modular strategy for generating a supramolecular, multifunctional, and stimuli-responsive nanoDDS through docking a parental core nanoDDS with various daughter function-prebuilt modules. Doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as the parental nanocore are wrapped by poly(ß-cyclodextrin) (PCD) as a gatekeeper through host-guest interactions between cyclodextrin units and pyridine groups of pyridine-disulfide bonds that confers pH/redox dual responsiveness, thus constructing stimuli-responsive nanoDDS (DOX@PRMSNs). Meanwhile, PCD's free cyclodextrin is tightly caged by adamantyl (Ad)-terminated daughter modules via host-guest interactions, achieving convenient multifunctionalization of this nanoDDS. DOX@PRMSNs rapidly released DOX in lysosomal pH/redox microenvironment, potently killing drug-resistant cancer cells. Further, three different types of Ad-terminated daughter modules, including two targeting ligands (Ad-PEG-FA and Ad-PEG-LA), a cationic polymer (Ad-PEI), and a fluorescence agent (Ad-FITC), are utilized to functionalize PRMSNs via cyclodextrin-Ad self-assembly, endowing the nanoDDS with cell-targeting capability, gene codelivery property, and imaging function. Thus, this work develops a supramolecular modular self-assembly approach for constructing and multifunctionalizing stimuli-responsive "smart" nanoDDSs.