Blockade of CD73 potentiates radiotherapy antitumor immunity and abscopal effects via STING pathway.

Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC.

[Effects of stress on the structure and function of microglia].

The activation of stressors can disrupt the body's homeostasis, leading to the release of stress hormones such as epinephrine, noradrenaline, and glucocorticoids. Moreover, emerging evidence highlights the profound impact of stress on microglia, which are specialized macrophages residing in the brain's parenchyma. Following stress, microglia exhibit notable morphological activation and increased phagocytic activity. Microglia express various receptors that enable them to respond to stress hormones originating from both central and peripheral sources, thereby exerting pro-inflammatory or anti-inflammatory effects. In this article, we review the advancements in studying the structural and functional changes of microglia induced by exposure to stressors. Additionally, we explore the role of stress hormones in mediating the effects of these stressors on microglia.

The relationship between socioeconomic status, medical accessibility, hope and psychological resilience of caregivers of children with chronic kidney disease in China: structural equation model.

BACKGROUND: Chronic kidney disease (CKD) is the third most common cause of death after cancer and heart disease. The continuous treatment of children with CKD was greatly challenged during the COVID-19 pandemic, which significantly impacted the CKD children's prognosis and the caregivers' psychological status. However, the influence mechanism of socioeconomic status, medical delay duration, traffic pressure, and online consultation duration on caregivers' hope and psychological resilience still lacks relevant evidence. METHODS: This study investigated the general social information, hope, and psychological resilience of 247 caregivers with CKD in 13 provinces of China in March 2020. Factor analysis and an exploratory Structural Equation Model ( SEM ) were used to find the best-fit model, and Bootstrapping was used to calculate the 95% CI of indirect effects. RESULTS: The factor analysis obtained four common factors, namely, socioeconomic status (annual family income, education, and career stability), medical accessibility (online consultation duration, medical delay duration, and traffic pressure), hope (positive attitude, positive action, and intimate relationship) and psychological resilience (optimism, tenacity, and strength), with the cumulative contribution rate of 65.34%. Bootstrapping obtains the socioeconomic status ß = 0.30 (95% CI [0.14, 0.47], P = 0.002), medical accessibility ß = 0.31 (95% CI [0.12, 0.47], P = 0.002), and hope ß = 0.40 (95% CI [0.27, 0.52], P = 0.002) has a direct impact on psychological resilience of CKD children caregivers, followed by medical accessibility ß = 0.20 (95% CI [0.10, 0.38], P = 0.001) and hope ß = 0.23 (95% CI [0.16, 0.32], P = 0.001) plays a mediating role between socioeconomic status and psychological resilience. The indirect impact effect ß = 0.35 (95% CI [0.25, 0.50], P = 0.001) is greater than the direct impact effect ß = 0.30 (95% CI [0.14, 0.47], P = 0.002). CONCLUSIONS: Sufficient attention should still be given to children with immunodeficiency after the COVID-19 pandemic, such as CKD, to avoid infection of deadly. Secondly, the government should vigorously develop Primary medical institutions to ensure efficient treatment of severe patients in tertiary hospitals; Finally, the professional literacy of medical workers in remote diagnosis and treatment should be improved to enhance the country's emergency response capacity for similar major public events and the requirements for normalised epidemic prevention and control.

Stimuli-responsive AIEgens with an ultra acidochromic scope for self-reporting soft actuators.

This study develops a series of NBI-based acidochromic AIEgens engineered for ultra-wide acidochromic scope in self-reporting soft actuators, establishing the relationship between the photophysical properties and structural configurations of the AIEgens, further investigating their acidochromic behavior and fabricating acidity monitoring chips. The acidochromic behaviors were thoroughly investigated, and high-precision acidity monitoring chips were fabricated. We confirmed the protonation order of nitrogen atoms within the molecules and elucidated the acidochromic mechanisms through DFT and 1H NMR analyses. Utilizing these findings, we designed acid-driven hydrogel-based biomimetic actuators that can self-report and control the release of heavy loads under acidic conditions. These actuators hold significant potential for applications in targeted drug delivery within acidic biological environments, controlled release systems, and specialized transportation of heavy loads under acidic conditions.

Green Polymer Electrolytes Prepared by a Cost-Effective Approach.

The preparation of solid polymer electrolytes (SPEs) using poly(ethylene oxide) (PEO) typically involves incorporating fillers or undergoing chemical modifications to reduce crystallinity and enhance conductivity. PEO with a lower molecular weight, known as polyethylene glycol (PEG), exhibits higher conductivity, despite weaker mechanical strength. It is commonly employed as a plasticizer to improve the conductivity of SPEs or to fabricate PEG-based gel polymer electrolytes (GPEs). In this study, we use a straightforward approach to create innovative SPEs by blending liquid polymer electrolytes (LPEs), particularly low-molecular-weight polyethylene glycol (PEG), with a molecular weight of 400 g/mol, and sustainable poly(l-lactide) (PLLA). Solid PEG/PLLA forms are achieved by introducing 30 wt % of PLLA. Subsequently, the addition of lithium salts results in the development of novel PEG/PLLA SPEs. Another focal point of this study involves incorporating 1,3:2,4-dibenzylidene sorbitol (DBS) into these PEG/PLLA systems. DBS, an organic gelator derived from natural sugars, demonstrates self-assembly, leading to the formation of a nanofibrillar network structure. Leveraging DBS's ability to form organogels in liquid organic environments, we facilitate the transformation of low PLLA content LPEs into innovative solvent-free GPEs. Our prepared PEG/PLLA SPEs exhibited a maximum conductivity value of 4.39 × 10-5 S/cm, approximately five times higher than that of neat PEG (10000 g/mol) SPEs. The ionic conductivity exhibited a declining trend as the content of PLLA and DBS increased. However, there was an improvement in electrochemical stability. Furthermore, the incorporation of PLLA and DBS into electrolytes contributed to enhanced mechanical support and stability within the electrolyte layer. This, in turn, mitigated capacity decay and improved the cycling performance of assembled lithium-ion cells.

Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein.

Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.

Modulation of histone acetylation enables fully mechanized hybrid rice breeding.

Hybrid rice has achieved high grain yield and greatly contributes to food security, but the manual-labour-intensive hybrid seed production process limits fully mechanized hybrid rice breeding. For next-generation hybrid seed production, the use of small-grain male sterile lines to mechanically separate small hybrid seeds from mixed harvest is promising. However, it is difficult to find ideal grain-size genes for breeding ideal small-grain male sterile lines without penalties in the number of hybrid seeds and hybrid rice yield. Here we report that the use of small-grain alleles of the ideal grain-size gene GSE3 in male sterile lines enables fully mechanized hybrid seed production and dramatically increases hybrid seed number in three-line and two-line hybrid rice systems. The GSE3 gene encodes a histone acetyltransferase that binds histones and influences histone acetylation levels. GSE3 is recruited by the transcription factor GS2 to the promoters of their co-regulated grain-size genes and influences the histone acetylation status of their co-regulated genes. Field trials demonstrate that genome editing of GSE3 can be used to immediately improve current elite male sterile lines of hybrid rice for fully mechanized hybrid rice breeding, providing a new perspective for mechanized hybrid breeding in other crops.

Correlation between abnormal cellular immune and changes of magnetic resonance spectroscopy in patients with Alzheimer's disease.

BACKGROUND: Evidence from previous studies indicates that neuroinflammation contributes to the onset of Alzheimer's Disease (AD). Moreover, cellular dysfunction is induced by impaired signaling of neurotransmitters. This study aimed to explore the correlation between cellular immune dysfunction and neurotransmitter changes through cranial Magnetic Resonance Spectroscopy (MRS) in AD patients. METHODS: Here, 32 AD, 40 Vascular Dementia (VD), and 35 Non-Dementia Elderly Control (NDE) cases were enrolled. Flow cytometry was performed to characterize lymphocyte subsets in plasma samples. The IL-1ß and Caspase-1 levels were detected by ELISA. The NLRP3 expression level was measured by Western Blot (WB). The equivalence of N-acetylaspartate (NAA), Creatine (Cr), Choline (Cho), and Inositol (MI) in bilateral hippocampi of patients was examined by MRS. The association of NAA/Cr or MI/Cr ratios with the proportion of T lymphocyte subsets or NK cell subsets was determined through single-factor correlation analysis. RESULTS: The proportion of T lymphocyte subsets was significantly lower in the AD group than in the NDE group (P < 0.01). On the other hand, the Caspase-1, NLRP3, and IL-1ß protein expression levels were significantly higher in the AD group than in the other groups. Further analysis showed that the NAA/Cr ratio was lower in the AD group than in the NDE group. Additionally, a significant positive correlation was found between the NAA/Cr ratio and the MMSE score (r = 0.81, P < 0.01). Moreover, a significant positive correlation was observed between the NAA/Cr and T lymphocyte ratios. The NAA/Cr ratio was significantly negatively correlated with the proportion of NK cells in the blood (r = ï¼0.83, P < 0.01). A significant negative correlation was also recorded between the MI/Cr and T cell ratios in blood samples. CONCLUSIONS: Impaired cellular immune dysfunction in AD patients was significantly correlated with abnormal MRS. Neuroimmune dysfunction may contribute to the pathogenesis of AD and alter the metabolism of neurotransmitters such as aspartic acid and MI in the brains of AD patients. TRIAL REGISTRATION: Not applicable.

Effect of calcium and phosphorus on ammonium and nitrate nitrogen adsorption onto iron (hydr)oxides surfaces: CD-MUSIC model and DFT computation.

Calcium (Ca2+) and phosphorous (PO43-) significantly influence the form and effectiveness of nitrogen (N), however, the precise mechanisms governing the adsorption of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) are still lacking. This study employed batch adsorption experiments, charge distribution and multi-site complexation (CD-MUSIC) models and density functional theory (DFT) calculations to elucidate the mechanism by which Ca2+ and PO43- affect the adsorption of NH4+-N and NO3--N on the goethite (GT) surface. The results showed that the adsorption of NH4+-N on the GT exhibited an initial increase followed by a decrease as pH increased, peaking at a pH of 8.5. Conversely, the adsorption of NO3--N decreased with rising pH. According to the CD-MUSIC model, Ca2+ minimally affected the NH4+-N adsorption on the GT but enhanced NO3--N adsorption via electrostatic interaction, promoting the adsorption of ≡FeOH-NO3- and ≡Fe3O-NO3- species. Similarly, PO43- inhibited the adsorption of ≡FeOH-NO3- and ≡Fe3O-NO3- species. However, PO43- boosted NH4+-N adsorption by facilitating the formation of ≡Fe3O-NH4+ via electrostatic interaction and site competition. DFT calculations indicates that although bidentate phosphate (BP) was beneficial to stabilize NH4+-N than monodentate phosphate (SP), SP-NH4+ was the main adsorption configuration at pH 5.5-9.5 owing the prevalence of SP on the GT surface under site competition of NH4+-N. The results of CD-MUSIC model and DFT calculation were verified mutually, and provide novel insights into the mechanisms underlying N fixation and migration in soil.

High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration.

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

Patterns of unhealthy lifestyle and their associations with depressive and anxiety symptoms among Chinese young adults: A latent class analysis.

BACKGROUND: There is little evidence on the association between patterns of unhealthy lifestyle and mental health among young adults. METHOD: This study included a total of 28,978 young adults aged 18 to 44 years old in Guangdong province in south China, which was conducted from September to December in 2022. We used latent class analysis to classify the patterns of unhealthy lifestyle among young adults and used multiple logistic regression to explore their associations with depressive and anxiety symptoms. RESULT: The weighted prevalence of depressive and anxiety symptoms were 28.0 % and 19.5 %, respectively. The cumulative effect of unhealthy lifestyles on depressive and anxiety symptoms was significant. Five patterns of unhealthy lifestyle were classified. Compared to the relatively healthy lifestyle class, the class with more unhealthy lifestyles (OR = 6.54, 95 % CI: 5.70-7.51) and insufficient sleep (OR = 6.16, 95 % CI: 4.92-7.70) had higher risk for depressive and anxiety symptoms. Meaningfully, having adequate mental health literacy could reduce the risk of depressive and anxiety symptoms from unhealthy lifestyle by half. LIMITATIONS: The cross-section design study limited causal inferences, and the self-report information may lead to recall bias. CONCLUSIONS: Unhealthy lifestyles have a negative impact on depressive and anxiety symptoms through independent, cumulative and combined effects, and they could be interrelated. Unhealthy lifestyle patterns differed in younger population by socio-demographic characteristics and mental health literacy. Health-care professionals and policymakers may provide programs to intervene multiple unhealthy lifestyles and improve mental health literacy by integrating healthy lifestyle education to promote youngers' mental health.

Electrochemical Biosensor for Protein Concentration Monitoring Using Natural Wood Evaporation for Power Generation.

A high-sensitivity, low-cost, self-powered biomass electrochemical biosensor based on the "evaporating potential" theory is developed for protein detection. The feasibility of experimental evaluation methods was verified with a probe protein of bovine serum albumin. The sensor was then used to detect lung cancer marker CYFRA21-1, and the potential of our sensor for clinical diagnosis was demonstrated by serum analysis. This work innovatively exploits the osmotic power generation capability of natural wood to construct a promising electrochemical biosensor that was driven by kinetics during testing. The detection methods used for this sensor, chronoamperometry and AC impedance, showed potential for quantitative analysis and specific detection, respectively. Furthermore, the sensor could facilitate new insights into the development of high-sensitivity, low-cost, and easy-to-use electrochemical biosensors.

Recent progress on the construction and application of dithienylethene-based photochromic AIEgens.

Photochromic fluorescent materials have rapidly developed as a new class of intelligent materials, offering a unique combination of traditional photochromic and organic fluorescent materials. These materials possess remarkable photoresponsiveness that can be observed by the naked eye and exhibit fluorescence color change. Consequently, they have found widespread applications in various domains, including molecular switches, logic encryption, medical diagnosis and treatment, and biosensors. Among the multitude of photochromic systems, those based on dithienylethenes (DTEs) have garnered significant attention due to their exceptional photochromic efficiency, commendable reversible photoresponse and fatigue resistance, as well as excellent photostability and thermal stability. Nevertheless, these photochromic fluorescent materials continue to grapple with the issue of aggregation-caused quenching (ACQ), a common problem faced by traditional fluorescent materials. Therefore, the integration of DTE systems with aggregation-induced emission (AIE) systems presents a promising solution to tackle this predicament, enabling an improved quantum yield for photochromic fluorescent materials in their aggregated state and broadening their range of applications. This review comprehensively summarizes and evaluates the construction strategies and application prospects of DTE-based photochromic AIE luminogens (AIEgens) in recent years, while also providing an outlook on their future development.

Dual-Stimulus-Driven Dynamically Controllable [3]Rotaxane with Tunable Organic Room-Temperature Phosphorescence.

A dual-stimulus-driven stiff-stilbene-based dynamic [3]rotaxane has been facilely developed using the threading-stoppering strategy and exhibits reversible shuttling motions and bidirectional rotations upon encountering acid-base and distinct light stimulations, respectively. Herein, the two dibenzo-24-crown-8 macrocycles can undergo reversible switching motion between two different stations along the axle suffered from acid-base stimulation, and simultaneously, the two rotaxanes can also perform cis-trans rotations upon irradiation with distinct light. In other words, the constructed rotaxanes can conduct two modes of regular motions without interference. Interestingly, reciprocating switching motion of the rings along the axle enabled the rotaxanes to exhibit controllable and reversible photoisomerization speed, conversion yield, and quantum yield. Crucially, these rotaxanes also manifest adjustable solid-state organic room-temperature phosphorescence (RTP) and photoluminescence stimulated by dual factors (acid-base and diverse light), which are further applied in information encryption and anticounterfeiting. The presented study provides an instructive way for precisely boosting photoisomerization performances and the fabrication of dual-stimuli-induced molecular machines with functions of two-mode mechanical motions and controllable pure organic RTP switches.

Bioinformatics approach to identify the hub gene associated with COVID-19 and idiopathic pulmonary fibrosis.

The coronavirus disease 2019 (COVID-19) has developed into a global health crisis. Pulmonary fibrosis, as one of the complications of SARS-CoV-2 infection, deserves attention. As COVID-19 is a new clinical entity that is constantly evolving, and many aspects of disease are remain unknown. The datasets of COVID-19 and idiopathic pulmonary fibrosis were obtained from the Gene Expression Omnibus. The hub genes were screened out using the Random Forest (RF) algorithm depending on the severity of patients with COVID-19. A risk prediction model was developed to assess the prognosis of patients infected with SARS-CoV-2, which was evaluated by another dataset. Six genes (named NELL2, GPR183, S100A8, ALPL, CD177, and IL1R2) may be associated with the development of PF in patients with severe SARS-CoV-2 infection. S100A8 is thought to be an important target gene that is closely associated with COVID-19 and pulmonary fibrosis. Construction of a neural network model was successfully predicted the prognosis of patients with COVID-19. With the increasing availability of COVID-19 datasets, bioinformatic methods can provide possible predictive targets for the diagnosis, treatment, and prognosis of the disease and show intervention directions for the development of clinical drugs and vaccines.

Evaluation and optimization of ecological landscape pattern for urban agglomeration in the Pearl River Delta, China.

The evaluation and optimization of landscape ecological pattern has important implications for the accurate improvement of forest quality and high-quality urban development in the Pearl River Delta urban agglomeration. Based on the "one map" data and digital elevation model data of forest resource management in 2021, we evaluated and optimized landscape ecological pattern of the Pearl River Delta urban agglomeration by morphological spatial pattern analysis and minimum cumulative resistance model. The results showed that there were 435861 patches in the Pearl River Delta urban agglomeration that could be used as ecological source area, covering an area of 7346.60 km2 and accounting for 13.4% of the Pearl River Delta area. Thirty patches were selected as the ecological source area of the study area by using the area and patch importance index, covering an area of 2792.59 km2 and accounting for 5.1% of the Pearl River Delta area. The overall natural environment of the Pearl River Delta urban agglomeration was excellent. The ecological resistance level was small. The peripheral ecological resistance was low. The core ecological resistance was high. There was still a large room for adjustment of stand types and landscape patterns, which should be optimized by adjusting the composition and spatial distribution of tree species. The ecological network of the Pearl River Delta urban agglomeration was optimized with 30 ecological sources, 103 key ecological corridors, and 95 ecological nodes. The improvement rates of the optimized probability of connectivity index and integral index of connectivity index were 297.5% and 695.1%, respectively. The optimization results could effectively connect the ecological sources and spread the ecological service functions of ecological sources.

Rational design of MOF@COF composites with multi-site functional groups for enhanced elimination of U(VI) from aqueous solution.

Both environment and human beings were menaced by the widespread application of radioactive uranium, high-performance and effective elimination of uranium from wastewater is of important meaning for development of environmental sustainability in the future. In this study, the water-stable MOF material and the highly crystalline COF were compounded by a mild hydrothermal strategy, which achieved efficient removal of U(VI) through the synergistic effect. The composites showed the characteristics of both COFs and MOFs, which will possess higher stability, larger surface area and faster adsorption efficiency that cannot be carried out by a single component. Batch experiments and characterizations (SEM, TEM, XRD, FT-IR, BET, XPS, etc.) indicated that UiO-66-NH2@LZU1 had more stable and multi-layer pore structure and rich active functional groups. The Langmuir model and the pseudo-second-order kinetics fitting was more suitable for the U(VI) elimination process. The greatest uranium adsorbing capacity of UiO-66-NH2@LZU1 (180.4 mg g-1) was observed to exceed the UiO-66-NH2 (108.8 mg g-1) and COF-LZU1 (65.8 mg g-1), which reached the excellent hybrid effects. Furthermore, FT-IR and XPS analyses confirmed that the most nitrogen-containing group from COF-LZU1 and oxygen-containing group of UiO-66-NH2 could be combined with U(VI). In addition, electrostatic interaction was also a mechanism during the removal process. This work displayed that UiO-66-NH2@LZU1 was a prospective hybrid material for radioactive waste remediation. The compound method and application mentioned in this work had provided a theoretical basis for designing and developing multi-functional composite adsorbents, which contributed to the development of new materials for radioactive wastewater treatment technologies.

Voluntary wheel exercise ameliorates cognitive impairment, hippocampal neurodegeneration and microglial abnormalities preceded by demyelination in a male mouse model of noise-induced hearing loss.

Acquired peripheral hearing loss (APHL) in midlife has been identified as the greatest modifiable risk factor for dementia; however, the pathophysiological neural mechanisms linking APHL with an increased risk of dementia remain to be elucidated. Here, in an adult male mouse model of noise-induced hearing loss (NIHL), one of the most common forms of APHL, we demonstrated accelerated age-related cognitive decline and hippocampal neurodegeneration during a 6-month follow-up period, accompanied by progressive hippocampal microglial aberrations preceded by immediate-onset transient elevation in serum glucocorticoids and delayed-onset sustained myelin disruption in the hippocampus. Pretreatment with the glucocorticoid receptor antagonist RU486 before stressful noise exposure partially mitigated the early activation of hippocampal microglia, which were present at 7 days post noise exposure (7DPN), but had no impact on later microglial aberrations, hippocampal neurodegeneration, or cognitive decline exhibited at 1 month post noise exposure (1MPN). One month of voluntary wheel exercise following noise exposure barely affected either the hearing threshold shift or hippocampal myelin changes but effectively countered cognitive impairment and the decline in hippocampal neurogenesis in NIHL mice at 1MPN, paralleled by the normalization of microglial morphology, which coincided with a reduction in microglial myelin inclusions and a restoration of microglial hypoxia-inducible factor-1α (HIF1α) expression. Our results indicated that accelerated cognitive deterioration and hippocampal neuroplastic decline following NIHL are most likely driven by the maladaptive response of hippocampal microglia to myelin damage secondary to hearing loss, and we also demonstrated the potential of voluntary physical exercise as a promising and cost-effective strategy to alleviate the detrimental impact of APHL on cognitive function and thus curtail the high and continuously increasing global burden of dementia. Furthermore, the findings of the present study highlight the contribution of myelin debris overload to microglial malfunction and identify the microglial HIF1α-related pathway as an attractive candidate for future comprehensive investigation to obtain a more definitive picture of the underlying mechanisms linking APHL and dementia.

Effects of chemical oxygen demand/nitrogen on electrochemical performances and denitrification efficiency in single-chamber microbial fuel cells: Insights from electron transfer and bacterial communities.

The electrochemical performances and denitrification efficiency of microbial fuel cells (MFCs) are often limited by chemical oxygen demand/nitrogen (COD/N) of wastewater. To overcome this limitation, single-chamber air cathode MFCs with varying COD/N (16/1, 8/1, and 4/1) were established to investigate their electrochemical performances, denitrification efficiency, and bacterial communities. The optimal COD/N for maximizing electricity generation and denitrification efficiency was 8/1, as supported by the greatest corrected coulomb efficiency (13.6%) and electron transfer rate (2.36 C/h for electricity generation, 39.77 C/h for denitrification). As COD/N decreased, the electrochemically active genus Geobacter was replaced by the denitrifying genera Un._f_Burkholderiaceae, Dechlorosoma, and Petrimonas. These results indicated that the efficiency of electricity generation and denitrification was not solely determined by the abundance of electrochemically active and denitrifying bacteria. The presence of a faster electron transfer pathway, possibly direct interspecies electron transfer, enhanced simultaneous electricity generation and denitrification in MFCs with COD/N of 8/1.

Efficient decontamination of organic pollutants from wastewater by covalent organic framework-based materials.

Covalent organic frameworks (COFs), assembling through covalent bonds, are a rising class of porous materials. Nowadays, various COFs are widely applied in organic pollutants decontamination due to the outstanding capabilities of large surface area, multiple functional groups, porous structure, excellent absorptivity, flexible design and so on. This review concentrates on the applications of COFs in different decontamination technologies such as solid-phase extraction, membrane filtration and sieving, adsorption, and catalysis reaction. The factors influencing water chemistry, such as pH, temperature, salt concentration and natural organic matter, are summarized in terms of their impact on decontamination performance and the extraction mechanisms for the diverse analytes. The interaction mechanisms between COFs and organic pollutants were hydrogen bonding, π-π stacking, hydrophilic, hydrophobic, and electrostatic interactions. Furthermore, a perspective on current obstacles and upcoming developments of COFs for organic pollutant removal has been provided. Due to their adaptable and versatile design as well as elaborate and diverse functionalization, COFs possess significant possibility in ameliorating environmental pollution.