Porous Organic Cage-Based Quasi-Solid-State Electrolyte with Cavity-Induced Anion-Trapping Effect for Long-Life Lithium Metal Batteries.

Porous organic cages (POCs) with permanent porosity and excellent host-guest property hold great potentials in regulating ion transport behavior, yet their feasibility as solid-state electrolytes has never been testified in a practical battery. Herein, we design and fabricate a quasi-solid-state electrolyte (QSSE) based on a POC to enable the stable operation of Li-metal batteries (LMBs). Benefiting from the ordered channels and cavity-induced anion-trapping effect of POC, the resulting POC-based QSSE exhibits a high Li+ transference number of 0.67 and a high ionic conductivity of 1.25 × 10-4 S cm-1 with a low activation energy of 0.17 eV. These allow for homogeneous Li deposition and highly reversible Li plating/stripping for over 2000 h. As a proof of concept, the LMB assembled with POC-based QSSE demonstrates extremely stable cycling performance with 85% capacity retention after 1000 cycles. Therefore, our work demonstrates the practical applicability of POC as SSEs for LMBs and could be extended to other energy-storage systems, such as Na and K batteries.

DCC, a potential target for controlling fear memory extinction and hippocampal LTP in male mice receiving single prolonged stress.

Post-traumatic stress disorder (PTSD) is a severe stress-dependent psychiatric disorder characterized by impairment of fear memory extinction; however, biological markers to determine impaired fear memory extinction in PTSD remain unclear. In male mice with PTSD-like behaviors elicited by single prolonged stress (SPS), 19 differentially expressed proteins in the hippocampus were identified compared with controls. Among them, a biological macromolecular protein named deleted in colorectal cancer (DCC) was highly upregulated. Specific overexpression of DCC in the hippocampus induced similar impairment of long-term potentiation (LTP) and fear memory extinction as observed in SPS mice. The impairment of fear memory extinction in SPS mice was improved by inhibiting the function of hippocampal DCC using a neutralizing antibody. Mechanistic studies have shown that knocking down or inhibiting µ-calpain in hippocampal neurons increased DCC expression and induced impairment of fear memory extinction. Additionally, SPS-triggered impairment of hippocampal LTP and fear memory extinction could be rescued through activation of the Rac1-Pak1 signaling pathway. Our study provides evidence that calpain-mediated regulation of DCC controls hippocampal LTP and fear memory extinction in SPS mice, which likely through activation of the Rac1-Pak1 signaling pathway.

Increased matrix stiffness in pituitary neuroendocrine tumors invading the cavernous sinus is activated by TAFs: focus on the mechanical signatures.

PURPOSE: Pituitary neuroendocrine tumors (PitNETs) with invasion of the cavernous sinus (CS) are particularly challenging to treat. Tumor associated fibroblasts (TAFs) are recognized for their pivotal role in reprogramming extracellular matrix (ECM). Herein, we aimed to explore the potential involvement of TAFs in ECM reprogramming and elucidate the underlying mechanism involved. METHODS: We applied dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to measure tumor vessel permeability and applied atomic force microscopy (AFM) to measure the matrix stiffness of PitNETs located in both CS and sella turcica (ST). Western blotting, immunofluorescence, immunohistochemistry, and quantitative RT-PCR were utilized to analyze the ECM components. Proteomic biochemical analysis was utilized to uncover potential mechanisms governing ECM dynamics. RESULTS: We found that PitNETs in the CS were stiffer than those in the ST. Increased ECM stiffness within the CS facilitated the acquisition of stem-like properties, enhanced proliferation, and induced epithelial-to-mesenchymal transition (EMT) of GH3 cells. Furthermore, the expression levels of lysyl oxidase (LOX), matrix metallopeptidase 2 (MMP2) and MMP9 in pituitary adenoma cells increased in the stiffer matrix. Proteomic analysis suggested TAFs were activated in the CS area and contributed enhanced matrix stiffness by secreting Col-1 and Col-3. Furthermore, mTOR pathway was activated under higher matrix stiffness and the migration and invasion of GH3 cells be repressed by mTOR inhibitor. CONCLUSION: These findings demonstrated that activated TAFs contributed to stiffer matrix and increased ECM stiffness stimulating mTOR pathway in pituitary tumor cells. Our study indicated that mTOR inhibitor was a promising treatment strategy from the standpoint of PitNET biomechanical properties.

Novel mechanisms of Anshen Dingzhi prescription against PTSD: Inhibiting DCC to modulate synaptic function and inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Anshen Dingzhi prescription (ADP), documented in "Yi Xue Xin Wu", is a famous prescription for treating panic-related mental disorders such as post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which ADP intervened in PTSD-like behaviors. METHODS: A mouse model of single prolonged stress (SPS) was established to evaluate the ameliorative effects and mechanisms of ADP on PTSD. Behavioral tests were used to assess PTSD-like behaviors in mice; transmission electron microscopy was used to observe changes in the ultrastructure of hippocampal synapses, and western blot, immunofluorescence, and ELISA were used to detect the expression of hippocampal deleted in colorectal cancer (DCC) and downstream Ras-related C3 botulinum toxin substrate 1 (Rac1) - P21-activated kinase 1 (PAK1) signal, as well as levels of synaptic proteins and inflammatory factors. Molecular docking technology simulated the binding of potential brain-penetrating components of ADP to DCC. RESULTS: SPS induced PTSD-like behaviors in mice and increased expression of hippocampal netrin-1 (NT-1) and DCC on the 14th day post-modeling, with concurrent elevation in serum NT-1 levels. Simultaneously, SPS also decreased p-Rac1 level and increased p-PAK1 level, the down-stream molecules of DCC. Lentiviral overexpression of DCC induced or exacerbated PTSD-like behaviors in control and SPS mice, respectively, whereas neutralization antibody against NT-1 reduced DCC activation and ameliorated PTSD-like behaviors in SPS mice. Interestingly, downstream Rac1-PAK1 signal was altered according to DCC expression. Moreover, DCC overexpression down-regulated N-methyl-d-aspartate (NMDA) receptor 2A (GluN2A) and postsynaptic density 95 (PSD95), up-regulated NMDA receptor 2B (GluN2B) and increased neuroinflammatory responses. Administration of ADP (36.8 mg/kg) improved PTSD-like behaviors in the SPS mice, suppressed hippocampal DCC, and downstream Rac1-PAK1 signal, upregulated GluN2A and PSD95, downregulated GluN2B, and reduced levels of inflammatory factors NOD-like receptor protein 3 (NLRP3), nuclear factor kappa-B (NF-κB) and interleukin-6 (IL-6). Importantly, DCC overexpression could also reduce the ameliorative effect of ADP on PTSD. Additionally, DCC demonstrated a favorable molecular docking pattern with the potential brain-penetrating components of ADP, further suggesting DCC as a potential target of ADP. CONCLUSION: Our data indicate that DCC is a key target for the regulation of synaptic function and inflammatory response in the onset of PTSD, and ADP likely reduces DCC to prevent PTSD via modulating downstream Rac1-PAK1 pathway. This study provides a novel mechanism for the onset of PTSD and warrants the clinical application of ADP.

Comparison of Financial Hardship and Healthcare Utilizations Associated with Cancer in the United States Medicare Programs during the COVID-19 Pandemic.

BACKGROUND: In the United States, Medicare beneficiaries diagnosed with cancer often face significant financial challenges due to the expensive nature of cancer treatments and increased cost-sharing responsibilities. However, there is limited knowledge regarding the financial hardships and healthcare utilizations faced by those enrolled in Medicare Advantage (MA) compared to those in traditional fee-for-service Medicare (TM) during the COVID-19 pandemic. Our study aims to investigate the subjective financial hardships experienced by individuals enrolled in TM and MA and to determine whether these two Medicare programs exhibit differences in healthcare utilization during the pandemic. METHODS: We utilized data from the 2020-2022 National Health Interview Survey (NHIS), focusing on nationally representative samples of cancer survivors aged 65 or older. Financial hardship was categorized into three distinct groups: material (e.g., problems with medical bills), psychological (e.g., worry about paying), and behavioral (e.g., delayed care due to cost). Healthcare utilization included wellness visits (preventive care), emergency care services, hospitalizations, and telehealth. We used survey design-adjusted analysis to compare the study outcomes between MA and TM. RESULTS: Among a weighted sample of 4.4 million Medicare beneficiaries with cancer (mean age: 74.9), 76% were enrolled in MA plans. Cancer survivors with a college degree (59.3% vs. 49.8%) and high family income (38.2% vs. 31.1%) were more likely to enroll in MA plans. There were no significant differences in any material, psychological, or behavioral financial hardship domains between beneficiaries with MA and TM plans except forgone counseling due to cost. For healthcare utilization measures, cancer survivors in MA were more likely than those in TM to have flu vaccination (77.2% vs. 70.1%) and experience lower hospitalizations (16.0% vs. 20.0%). However, there were no differences in other health service utilizations between MA and TM. CONCLUSION: While no significant differences were observed in any materialized, psychological, or behavioral financial hardships, older cancer survivors enrolled in MA plans were more likely to receive vaccinations and lower hospitalization rates during COVID-19. Although other preventive or primary care visits (i.e., wellness visits) were higher, their difference did not reach statistical significance. As MA grows in popularity, it is essential to consistently monitor and evaluate the performance and outcomes of Medicare plans for cancer survivors as we navigate the post-pandemic landscape.

Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

A Framework for Detecting False Data Injection Attacks in Large-Scale Wireless Sensor Networks.

False data injection attacks (FDIAs) on sensor networks involve injecting deceptive or malicious data into the sensor readings that cause decision-makers to make incorrect decisions, leading to serious consequences. With the ever-increasing volume of data in large-scale sensor networks, detecting FDIAs in large-scale sensor networks becomes more challenging. In this paper, we propose a framework for the distributed detection of FDIAs in large-scale sensor networks. By extracting the spatiotemporal correlation information from sensor data, the large-scale sensors are categorized into multiple correlation groups. Within each correlation group, an autoregressive integrated moving average (ARIMA) is built to learn the temporal correlation of cross-correlation, and a consistency criterion is established to identify abnormal sensor nodes. The effectiveness of the proposed detection framework is validated based on a real dataset from the U.S. smart grid and simulated under both the simple FDIA and the stealthy FDIA strategies.

Chiral BINOL-phosphate assembled single hexagonal nanotube in aqueous solution for confined rearrangement acceleration.

Creating microenvironments that mimic an enzyme's active site is a critical aspect of supramolecular confined catalysis. In this study, we employ the commonly used chiral 1,1'-bi-2-naphthol (BINOL) phosphates as subcomponents to construct supramolecular hollow nanotube in an aqueous medium through non-covalent intermolecular recognition and arrangement. The hexagonal nanotubular structure is characterized by various techniques, including X-ray, NMR, ESI-MS, AFM, and TEM, and is confirmed to exist in a homogeneous aqueous solution stably. The nanotube's length in solution depends on the concentration of chiral BINOL-phosphate as a monomer. Additionally, the assembled nanotube can accelerate the rate of the 3-aza-Cope rearrangement reaction by up to 85-fold due to the interior confinement effect. Based on the detailed kinetic and thermodynamic analyses, we propose that the chain-like substrates are constrained and pre-organized into a reactive chair-like conformation, which stabilizes the transition state of the reaction in the confined nanospace of the nanotube. Notably, due to the restricted conformer with less degrees of freedom, the entropic barrier is significantly reduced compared to the enthalpic barrier, resulting in a more pronounced acceleration effect.

Observation on Short-Term Therapeutic Effect of Electroacupuncture on Compensatory Hypertrophy Of Gastrocnemius Muscle: A Retrospective Cohort Study.

Objective: In Oriental women, having thick and short legs is a common posture problem, and having an imperfect lower leg shape is one of the factors that can cause feelings of inferiority. To address this issue, a retrospective cohort study was conducted to investigate the effectiveness of electroacupuncture in improving compensatory hypertrophy of the gastrocnemius muscle while also reducing side effects. The goal of this study is to improve the clinical treatment plan for this type of problem. Methods: This retrospective cohort study was conducted between December 2020 and March 2022 at the Changhai Hospital of Shanghai, Shanghai, China. This study included 80 patients who were divided into two equal groups - the infrared (IR) group and the electroacupuncture (EA) group, based on the type of treatment they received during the research. The EA group received electroacupuncture and infrared treatment, while the IR group used an infrared therapeutic instrument to irradiate their lower legs on both sides. The main outcome measures were 3 calf circumference levels and the cross-sectional area of the gastrocnemius muscle in two-dimensional ultrasound. The secondary outcome measure was the incidence of adverse events. Results: According to the data, before the treatment there were no statistically significant differences between the two groups in calf circumference and ultrasound gastrocnemius cross-sectional area. After the treatment, the value of each calf circumference level and ultrasound gastrocnemius cross-sectional area were significantly lower than the value collected before the treatment in the EA Group. However, there is no significant change in the data of the infrared therapeutic group before and after treatment. By comparing the data between the 2 groups we collected after the treatment, the value of each calf circumference level and ultrasound gastrocnemius cross-sectional area of the EA group is significantly lower than that of the IR group. Only 8 patients suffered from lower limb pain and other discomfort after treatment, and these symptoms did not cause dissatisfaction. Conclusion: Electroacupuncture is an effective treatment for compensatory hypertrophy of the gastrocnemius muscle.

Naturally aged polylactic acid microplastics stunted pakchoi (Brassica rapa subsp. chinensis) growth with cadmium in soil.

Biodegradable microplastics (BMPs) and cadmium (Cd) are posing threats to agro-systems especially to plants and current studies mostly used virgin BMPs to explore their ecological effects. However, effects of naturally aged BMPs and their combined effects with Cd on pakchoi are yet to be unraveled. Therefore, this study incubated naturally aged polylactic acid (PLA) MPs through soil aging process and investigated the single and combined effects of Cd and PLA MPs (virgin and aged) on pakchoi (Brassica rapa subsp. chinensis) morphology, antioxidant systems and soil microbial activities. Our results found that after being deposited in soil for six months, aged PLA (PLAa) MPs formed with a fractured surface, demonstrating more detrimental effects on pakchoi than virgin ones. PLA/PLAa MPs and Cd stunted pakchoi growth, caused oxidative stress and altered the biophysical environment in soil, separately. Moreover, co-existence of PLA/PLAa MPs and Cd caused greater damages to pakchoi than applied alone. The co-presence of PLAa MPs and Cd inhibited pakchoi biomass accumulation rate by 92.2 % compared with the no-addition group. The results unraveled here emphasized BMPs, especially aged BMPs, could trigger negative effects on agro-systems with heavy metals. These findings will give reference to future holistic assessments of BMPs' ecological effects.

General anesthesia alters the diversity and composition of the lung microbiota in rat.

BACKGROUND: The lung microbiome plays a crucial role in human health and disease. Extensive studies have demonstrated that the disturbance of the lung microbiome influences immune response, cognition, and behavior. The goal of this study was to investigate the effect of general anesthetics on lung microbiome. METHODS: Eight-week-old male SD rats received a continuous intravenous infusion of propofol or inhalation of isoflurane for 4 h. 16S rRNA gene amplification from BALF samples was used to investigate the changes in the lung microbiome after interventions. We further performed neurobehavioral assessments to find the differential strains' association with behavior disorder after isoflurane anesthesia. RESULTS: The absolute and relative quantitation of 16S rRNA sequencing data showed that isoflurane altered the diversity and abundance of the lung microbiome in rats more than propofol. Elusimicrobia increased significantly in the isoflurane group. Both EPM and OFT results showed that rats exhibited depression-like behaviors after inhalation of isoflurane. In addition, significant differences were found in the COG/KO/MetaCyc/KEGG pathway enrichment analyses among the groups. CONCLUSION: Continuous inhalation of isoflurane changed the diversity and composition of the lung microbiota in rats, resulting in post-anesthesia depression.

A Novel Diagnosis Scheme against Collusive False Data Injection Attack.

The collusive false data injection attack (CFDIA) is a false data injection attack (FIDA), in which false data are injected in a coordinated manner into some adjacent pairs of captured nodes of an attacked wireless sensor network (WSN). As a result, the defense of WSN against a CFDIA is much more difficult than defense against ordinary FDIA. This paper is devoted to identifying the compromised sensors of a well-behaved WSN under a CFDIA. By establishing a model for predicting the reading of a sensor and employing the principal component analysis (PCA) technique, we establish a criterion for judging whether an adjacent pair of sensors are consistent in terms of their readings. Inspired by the system-level fault diagnosis, we introduce a set of watchdogs into a WSN as comparators between adjacent pairs of sensors of the WSN, and we propose an algorithm for diagnosing the WSN based on the collection of the consistency outcomes. Simulation results show that the proposed diagnosis scheme achieves a higher probability of correct diagnosis.

The underlying mechanism of transcription factor IRF1, PRDM1, and ZNF263 involved in the regulation of NPPB rs3753581 on pulse pressure hypertension.

To investigate the correlation between NPPB gene variants and pulse pressure hypertension and the underlying regulatory mechanisms and try to confirm that NPPB may be a potential molecular target of gene therapy for pulse pressure hypertension. A total of 898 participants were recruited from the First Affiliated Hospital of Fujian Medical University and the plasmids with differential expression of NPPB were constructed. Genotype distribution of NPPB(rs3753581, rs198388, and rs198389)was analyzed and the expression of N-terminal pro-B-type natriuretic peptide(NT-proBNP) and renin-angiotensin -aldosterone system(RAAS) related indicators were identified in the groups studied. According to a genotype analysis, there was a significant difference in the genotype distribution of NPPB rs3753581 among the groups (P = 0.034). In logistic regression analysis, NPPB rs3753581 TT was associated with a 1.8-fold greater risk of pulse pressure hypertension than NPPB rs3753581 GG (odds ratio = 1.801; 95% confidence interval: 1.070-3.032; P = 0.027). The expression of NT-proBNP and RAAS related indicators in clinical and laboratory samples showed striking differences. The activity of firefly and Renilla luciferase in pGL-3-NPPB-luc (-1299G) was higher than pGL-3-NPPBmut-luc(-1299 T)(P < 0.05). The binding of NPPB gene promoter rs3753581 (-1299G) with transcription factors IRF1, PRDM1, and ZNF263 was predicted and validated by the bioinformatics software TESS and chromatin immunoprecipitation(P < 0.05). NPPB rs3753581 was correlated with genetic susceptibility to pulse pressure hypertension and the transcription factors IRF1, PRDM1, and ZNF263 may be involved in the regulation of NPPB rs3753581 promoter (-1299G) on the expression of NT-proBNP/RAAS.

MantaID: a machine learning-based tool to automate the identification of biological database IDs.

The number of biological databases is growing rapidly, but different databases use different identifiers (IDs) to refer to the same biological entity. The inconsistency in IDs impedes the integration of various types of biological data. To resolve the problem, we developed MantaID, a data-driven, machine learning-based approach that automates identifying IDs on a large scale. The MantaID model's prediction accuracy was proven to be 99%, and it correctly and effectively predicted 100,000 ID entries within 2 min. MantaID supports the discovery and exploitation of ID from large quantities of databases (e.g. up to 542 biological databases). An easy-to-use freely available open-source software R package, a user-friendly web application and application programming interfaces were also developed for MantaID to improve applicability. To our knowledge, MantaID is the first tool that enables an automatic, quick, accurate and comprehensive identification of large quantities of IDs and can therefore be used as a starting point to facilitate the complex assimilation and aggregation of biological data across diverse databases.

Engineering the Thermostability of a d-Carbamoylase Based on Ancestral Sequence Reconstruction for the Efficient Synthesis of d-Tryptophan.

Employing ancestral sequence reconstruction and consensus sequence analysis, the thermostability of a novel d-carbamoylase derived from Nitratireductor indicus (NiHyuC) was engineered through greedy-oriented iterative combinatorial mutagenesis. A mutant S202P/E208D/R277L (M4Th3) was obtained with significantly elevated thermostability. M4Th3 has a half-life of 36.5 h at 40 °C, about 28.5 times of 1.3 h of its parent M4. For the reaction at 40 °C, M4Th3 can catalyze 10 mM N-carbamoyl-d-tryptophan to produce d-tryptophan with a conversion ratio of 96.4% after 12 h, which is significantly higher than 64.1% of M4. MD simulation reveals that new hydrogen bonds emerging from E208D on the surface can increase the hydrophobicity of the protein, leading to improved stability. More importantly, R277L could contribute to enhanced interface stability of homodimeric M4. This study provides a thermostable d-carbamoylase for the "hydantoinase process", which has potential in the industrial synthesis of optically pure natural and non-natural amino acids.

Ginsenoside Rg1 in neurological diseases: From bench to bedside.

Ginseng has been used in China as a superior medicinal material for thousands of years that can nourish the five internal organs, calm the mind and benefit wisdom. Due to its anti-inflammatory, antioxidant and neuroprotective activities, one of the active components of ginseng, ginsenoside Rg1, has been extensively investigated in the remedy of brain disorders, especially dementia and depression. In this review, we summarized the research progress on the action mechanisms of Rg1 ameliorating depression-like behaviors, including inhibition of hyperfunction of hypothalamic-pituitary-adrenal (HPA) axis, regulation of synaptic plasticity and gut flora. Rg1 may alleviate Alzheimer's disease in the early phase, as well as in the middle-late phases through repairing dendrite, axon and microglia- and astrocyte-related inflammations. We also proposed that Rg1 could regulate memory state (the imbalance of working and aversive memory) caused by distinct stimuli. These laboratory studies would further the clinical trials on Rg1. From the prospective of drug development, we discussed the limitations of the present investigations and proposed our ideas to increase permeability and bioavailability of Rg1. Taken together, Rg1 has the potential to treat neuropsychiatric disorders, but a future in-depth investigation of the mechanisms is still required. In addition, drug development will benefit from the clinical trials in one specific neuropsychiatric disorder.

Detection of multidrug resistant pathogenic bacteria and novel complex class 1 integrons in campus atmospheric particulate matters.

Recent advances provided overwhelming evidence that atmospheric particulate matters carry a substantial amount of antibiotic resistance genes (ARGs). It has also been documented that polluted air facilitates transmission of bacterial pathogenesis and antimicrobial resistance (AMR). These investigations generally used culture-independent approaches which reveal sophisticated microbiomic and resistomic compositions in particulate matters, while culture-dependent methods directly demonstrating presence of live, functional bacteria has not been fully applied. In recent years, efforts undertaken worldwide managed to reduce air particulate matter pollution, leading to cleaner air in many parts of world, including China. Whether atmospheric particulate matters may still function as vehicles for pathogenic bacteria and AMR in improving air conditions is turning into an interesting question to address. In attempt to answer this question, a culture-dependent approach is used to find out the putative role of atmospheric particulate matters in relatively 'clean' air to transmit pathogenic bacteria and AMR in this work. By harvesting particulate matters in an unindustrialized and less-polluted university campus, culturing and identifying bacteria in particulate matters, and characterizing pathogenesis and AMR properties of these bacteria, interesting findings were made that even in relatively 'clean' air, antibiotic-resistant pathogenic bacteria are prevalent; and that mobile genetic elements including integrons are widespread. In particular, in air samples collected, multidrug-resistant hemolytic Bacillus strains that may pose significant health threat could be identified. Complex class 1 integrons, two of which carry novel antibiotic resistant gene cassette arrays, were also found for the first time in airborne bacteria, suggesting the danger of horizontal transfer of AMR in air. In conclusion, using culture-dependent methods, this work shows that atmospheric particulate matters are viable vehicles for the transmission of bacterial pathogenesis and AMR, and that even in relatively 'clean' air, the threat of airborne antibiotic-resistant pathogens is significant.

Fear of progression and its associated factors in parents of children undergoing cancer treatment: A cross-sectional study.

OBJECTIVE: Fear of progression (FoP) is a common psychosocial problem among adult cancer patients, but data on parents of children undergoing cancer treatment are scarce. This study aimed to determine the prevalence of FoP in parents of children undergoing cancer treatment and explore the associated factors. METHODS: Overall, 285 parents of children undergoing cancer treatment were recruited from three general hospitals in China. FoP in the parents was assessed using the Chinese version of the Fear of Progression Questionnaire-parent version (FoP-Q-SF/PR). Other questionnaires included the Self-Compassion Scale, Pittsburgh Sleep Quality Index, Posttraumatic Stress Disorder Checklist-Civilian Version, and items on socio-demographic and medical characteristics. Pearson correlation and multiple linear regression analysis were used to identify factors associated with FoP. RESULTS: A total of 75.1% of the participants showed dysfunctional levels of FoP. The mean FoP-Q-SF/PR score was 39.98 (standard deviation = 9.18). Parental FoP was significantly associated with a shorter time since diagnosis, lower levels of self-compassion, poor sleep quality, and severe posttraumatic stress symptoms (Adjusted R Squared = 0.369, F = 12.838, p < 0.01). CONCLUSIONS: FoP is a frequently reported problem among parents of children undergoing cancer treatment. In this cohort, parents of children with a shorter time since cancer diagnosis were at higher risk of suffering from FoP. Interventions to enhance self-compassion, improve sleep quality, and mitigate posttraumatic stress symptoms may help with the psychological adjustment and well-being of parents whose children are undergoing cancer treatment.

Evaluation of culturable 'last-resort' antibiotic resistant pathogens in hospital wastewater and implications on the risks of nosocomial antimicrobial resistance prevalence.

Antimicrobial resistance has been recognized as an important emerging environmental pollutant. 'Last-resort' antibiotics including tigecycline, polymyxin E, daptomycin, vancomycin and linezolid are the 'last line of defence' for antibiotic resistant pathogen infections. Therefore, the presence of 'last-resort' antibiotic resistant pathogens in hospital environments and the nosocomial transmission of 'last-resort' antibiotic resistance poses a grave threat to the well-being of patients. In this work, the extent of resistance to 'last-resort' antibiotics in culturable pathogens in hospital wastewater was investigated. Resistance to 'last-resort' antibiotics were quantified for 1384 culturable Enterobacteriaceae, Enterococcus, Staphylococcus, and Pseudomonas strains. With these investigations, several significant findings were made: (1) a very high level of resistance to 'last-resort' antibiotics was found; (2) multiple resistance to antibiotics, including 'last-resort' antibiotics, was prevalent; (3) a high level of 'last-resort' antibiotic resistance phenotype-genotype inconsistency was found, suggesting knowledge gap for resistance mechanisms; 4) tet(X4)-containing tigecycline-resistant Gram-positive pathogens were found for the first time; 5) wastewater treatment processes are effective in preventing the release of 'last-resort' antibiotic resistant pathogens to the environment. This investigation reveals the severe situation on 'last-resort' resistance in the hospital environment, and implies high risk for nosocomial transmission of 'last-resort' antibiotic resistant pathogens.

New Mutations in cls Lead to Daptomycin Resistance in a Clinical Vancomycin- and Daptomycin-Resistant Enterococcus faecium Strain.

Daptomycin (DAP), a last-resort antibiotic for treating Gram-positive bacterial infection, has been widely used in the treatment of vancomycin-resistant enterococci (VRE). Resistance to both daptomycin and vancomycin leads to difficulties in controlling infections of enterococci. A clinical multidrug-resistant Enterococcus faecium EF332 strain that shows resistance to both daptomycin and vancomycin was identified, for which resistance mechanisms were investigated in this work. Whole-genome sequencing and comparative genomic analysis were performed by third-generation PacBio sequencing, showing that E. faecium EF332 contains four plasmids, including a new multidrug-resistant pEF332-2 plasmid. Two vancomycin resistance-conferring gene clusters vanA and vanM were found on this plasmid, making it the second reported vancomycin-resistant plasmid containing both clusters. New mutations in chromosomal genes cls and gdpD that, respectively, encode cardiolipin synthase and glycerophosphoryl diester phosphodiesterase were identified. Their potential roles in leading to daptomycin resistance were further investigated. Through molecular cloning and phenotypic screening, two-dimensional thin-layer chromatography, fluorescence surface charge test, and analysis of cardiolipin distribution patterns, we found that mutations in cls decrease surface negative charges of the cell membrane (CM) and led to redistribution of lipids of CM. Both events contribute to the DAP resistance of E. faecium EF332. Mutation in gdpD leads to changes in CM phospholipid compositions, but cannot confer DAP resistance. Neither mutation could result in changes in cellular septa. Therefore, we conclude that the daptomycin resistance of E. faecium EF332 is conferred by new cls mutations. This work reports the genetic basis for vancomycin and daptomycin resistance of a multidrug-resistant E. faecium strain, with the finding of new mutations of cls that leads to daptomycin resistance.