Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates.

This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential via multicomponent hybridization to confront increasingly severe fungal invasion. Some prepared HNs exhibited considerable antifungal potency; especially nitrofuryl HN 4a (MIC = 0.001 mM) exhibited a potent antifungal activity against Candida albicans, which is 13-fold higher than that of fluconazole. Furthermore, nitrofuryl HN 4a displayed low cytotoxicity, hemolysis and resistance, as well as a rapid fungicidal efficacy. Preliminary mechanistic investigations revealed that nitrofuryl HN 4a could inhibit lactate dehydrogenase to decrease metabolic activity and promote the accumulation of reactive oxygen species, leading to oxidative stress. Moreover, nitrofuryl HN 4a did not exhibit membrane-targeting ability; it could embed into DNA to block DNA replication but could not cleave DNA. These findings implied that HNs are promising as novel structural scaffolds of potential multitargeting broad-spectrum antifungal candidates for treating fungal infection.

Enhancing the Interaction of Carbon Nanotubes by Metal-Organic Decomposition with Improved Mechanical Strength and Ultra-Broadband EMI Shielding Performance.

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 105 S m-1, and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 µm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices.

Cancer-Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self-Supply Capability for Tumor-Homing Phototherapy.

Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer-thylakoid hybrid membrane-camouflaged thulium oxide nanoparticles (Tm2O3) for tumor-homing phototherapy through dual-stage-light-guided ROS generation and oxygen self-supply is developed. Tm2O3 as a type II photosensitizer are viable for NIR-stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase-like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm2O3@TK-M/DiR group are effectively ablated following dual-stage-light irradiation, highlighting the promising potential of rare-earth element-based type II photosensitizers in various applications.

Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia / 中华儿科杂志

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

[Platycladi Semen oil ameliorates Aß_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota].

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aß_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aß_(25-35), 200 µmol·L~(-1), 0.15 µL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aß_(1-42)/Aß_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aß_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aß_(1-42)/Aß_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aß_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

Enhancing the Chemical Stability of MXene Through Synergy of Hydrogen Bond and Coordination Bond in Aqueous Solution.

MXenes with unique physicochemical properties have shown substantial potential in electromagnetic interference (EMI) shielding. However, the chemical instability and mechanical fragility of MXenes has become a major hurdle for their application. Abundant strategies have been dedicated to improving the oxidation stability of colloidal solution or mechanical properties of films, which always come at the expense of electrical conductivity and chemical compatibility. Here, hydrogen bond (H-bond) and coordination bond are employed to achieve chemical and colloidal stability of MXenes (0.1 mg mL-1 ) by occupying the reaction sites of Ti3 C2 Tx attacking of water and oxygen molecules. Compared to the Ti3 C2 Tx , the Ti3 C2 Tx modified with alanine via H-bond shows significantly improved oxidation stability (at room temperature over 35 days), while the Ti3 C2 Tx modified with cysteine by synergy of H-bond and coordination bond can be maintained even after 120 days. Simulation and experimental results verify the formation of H-bond and Ti-S bond by a Lewis acid-base interaction between Ti3 C2 Tx and cysteine. Furthermore, the synergy strategy significantly improves the mechanical strength of the assembled film (up to 78.1 ± 7.9 MPa), corresponding the increment of 203% compared to untreated one, almost without compromising the electrical conductivity and EMI shielding performance.

Early life climate and adulthood mental health: how birth seasonality influences depressive symptoms in adults.

BACKGROUND: Early life in-utero can have long-term influence on the mental health status of individuals in adulthood, such as depression. Age, gender, socio-economic status, education, and geography are demographic factors shown to be particularly vulnerable towards the development of depressive symptoms. In addition, climate risks on depression include sunlight, rain, and temperature. However, whether climate factors in early life have a long-term influence on depression related to demographic vulnerability remains unknown. Here, the present study explored the association between birth seasonality and adulthood depressive symptoms. METHODS: We employed data from the project of Chinese Labour-forces Dynamic Survey (CLDS) 2016, containing the epidemiological data of depressive symptoms with a probability proportional to size cluster and random cluster sampling method in 29 provinces of China. A final sample size of 16,185 participants was included. Birth seasonality included spring (March, April, and May), summer (June, July, and August), autumn (September, October, and November), and winter (December, January, and February). RESULTS: We found that born in Autumn peaked lowest rate of having depressive symptoms (16.8%) and born in Summer (vs. Autumn) had a significant higher ratio (OR = 1.14, 95%CI = 1.02, 1.29) when controlling for demographic variables. In addition, demographic odds ratio of having depressive symptoms differed between people born in different seasons, particular for age and geography. CONCLUSION: Our findings suggest that birth seasonality influences the sensitive link of depressive symptoms with age and geography. It implicates early life climate environment may play a role in the development of adulthood depressive symptoms.

Long-term survival influencing and risk factors in peritoneal dialysis patients: a single center study in Southwest China / 中华肾脏病杂志

Patients who initiated peritoneal dialysis (PD) in Sichuan Provincial People's Hospital from January 1, 2001 to December 31, 2013 were enrolled in the single center and retrospective study. Clinical and laboratory data were collected to analyze the long-term survival rates, technique survival rates and associated influencing factors. Patients were followed up until December 31, 2021 or endpoints occurred (death or stopping PD treatment). Kaplan-Meier survival curves were used to estimate survival rates and technique survival rates. Cox proportional hazards regression model was used to analyze the risk factors of death and technique failure in PD patients. A total of 373 patients were enrolled in the study, with age of (52.1±15.8) years old and 199 (53.4%) males. During the follow-up, 154 (41.3%) patients died, 72 (19.3%) patients transferred to hemodialysis, and 40 (10.7%) patients received kidney transplant. Kaplan-Meier survival curves revealed that overall survival rates of PD patients at 1, 3, 5, 7, and 10 years were 92.2%, 76.6%, 66.0%, 52.4% and 38.6%, respectively. Technique survival rates were 93.5%, 84.8%, 74.2%, 62.8% and 44.5% at 1, 3, 5, 7, and 10 years, respectively. Multivariate Cox regression model results showed that age ( HR=1.055, 95% CI 1.039-1.073, P<0.001), transfer from hemodialysis ( HR=2.212, 95% CI 1.514-3.231, P<0.001), episodes of peritonitis ( HR=2.141, 95% CI 1.194-3.837, P=0.011), Charlson comorbidity index ( HR=1.525, 95% CI 1.305-1.783, P<0.001), and baseline albumin ( HR=0.951, 95% CI 0.925-0.978, P<0.001) were independent influencing factors of survival in PD patients. Episodes of peritonitis ( HR=2.327, 95% CI 1.274-4.250, P=0.006) and Charlson comorbidity index ( HR=1.244, 95% CI 1.035-1.496, P=0.020) were independent influencing factors of technique survival in PD patients. PD patients have good early survival rates and technical survival rates, but long-term outcomes need to be further improved. Peritonitis is a major risk factor for low long-term survival rates and technical survival rates in PD patients.

Platycladi Semen oil ameliorates Aβ_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota / 中国中药杂志

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

Clinical usefulness of linked color imaging in identifying Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Accurate diagnosis of Helicobacter pylori (H. pylori) infection status is a crucial premise for eradication therapy, as well as evaluation of risk for gastric cancer. Recent progress on imaging enhancement endoscopy (IEE) made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H. pylori infection in real time. As a novel IEE modality, linked color imaging (LCI) has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone. AIM: To compare the efficacy of LCI for H. pylori active infection vs conventional white light imaging (WLI). METHODS: PubMed, Embase, Embase and Cochrane Library were searched up to the end of April 11, 2022. The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI. The calculation of sensitivity, specificity, and likelihood ratios were performed; symmetric receiver operator characteristic (SROC) curves and the areas under the SROC curves were computed. Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool. RESULTS: Seven original studies were included in this study. The pooled sensitivity, specificity, positive likelihood rate, and negative likelihood rate of LCI for the diagnosis of H. pylori infection of gastric mucosa were 0.85 [95% confidence interval (CI): 0.76-0.92], 0.82 (95%CI: 0.78-0.85), 4.71 (95%CI: 3.7-5.9), and 0.18 (95%CI: 0.10-0.31) respectively, with diagnostic odds ratio = 26 (95%CI: 13-52), SROC = 0.87 (95%CI: 0.84-0.90), which showed superiority of diagnostic efficacy compared to WLI. CONCLUSION: Our results showed LCI can improve efficacy of diagnosis on H. pylori infection, which represents a useful endoscopic evaluation modality for clinical practice.

[Mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination in treatment of bronchial asthma based on network pharmacology and experimental verification].

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-ß1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and ß-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and ß-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and ß-sitosterol are the candidate active components.

An unanticipated discovery of novel naphthalimidopropanediols as potential broad-spectrum antibacterial members.

Constructing a new antibacterial structural framework is an effective strategy to combat drug resistance. This work discovered a class of naphthalimidopropanediols (NIOLs) as a novel structural type of potential broad-spectrum antibacterial agents. Especially, NIOLs 9u, 12i, 15 against Staphylococcus aureus and NIOLs 9l, 13a against Pseudomonas aeruginosa showed excellent inhibitory activities, and they displayed high membrane selectivity from an electrostatic distinction on the membranes between bacteria and mammalian cells. These highly active NIOLs could effectually inhibit the bacterial growths, and relieve the resistance developments. Moreover, the facts of membrane depolarization, outer/inner membrane permeabilization and leakage of intracellular materials, demonstrated that these NIOLs could target and destroy the S. aureus or P. aeruginosa membranes. In particular, they could disrupt the antioxidant defense systems of S. aureus or P. aeruginosa through up-regulation of reactive oxygen species. Simultaneously, they could render the metabolic inactivation of the tested strains, and eradicate the formed biofilms and efficiently kill the strains within the biofilms. The in vitro and in vivo cytotoxicity assay indicated that these compounds possessed low toxicity. These findings of novel NIOLs as potential broad-spectrum antibacterial members provided a bright hope for conquering drug resistance.

Response mechanism of microorganisms to the inhibition of endogenous pollution release by calcium peroxide.

To further explore the response mechanism of microorganisms to the synchronous control of nitrogen and phosphorus release from sediments by CaO2, the spatiotemporal changes in the physical, chemical and biological indicators of the overlying water, interstitial water and sediments in each reactor were measured in the experiment. The experiment results showed that CaO2 could increase the ammonia monooxygenase activity, nitrite oxidase activity and Nitrospira abundance in the sediment near its dosing position, and enhanced the activities of nitrate reductase and nitrite reductase at a certain distance from the dosing position, thereby promoting nitrogen removal in sediments through the alternating process of nitrification and denitrification. At the same time, the increase of alkaline phosphatase activity and Saccharimonadales abundance in the test groups accelerated the hydrolysis of organic phosphorus, and the P immobilization in sediments was realized through the subsequent precipitation reaction of Ca2+ and PO43- under alkaline conditions. In addition, the enhanced activities of dehydrogenase and catalase ensured that CaO2 would not cause great killing effect on microorganisms when improving the hypoxic conditions and inhibiting endogenous release. As a result, the dissolved product of CaO2 such as Ca(OH)2 and H2O2 reduced the nutrients concentration and killed the algae, which kept the algae density and chlorophyll a concentration at a low level throughout the test groups. Therefore, this study systematically clarified the microbial mechanism of CaO2 synchronously controlling the release of nitrogen and phosphorus from sediments, which provided a new idea for the remediation of endogenous pollution in the water system.

P2X2 receptors in pyramidal neurons are critical for regulating vulnerability to chronic stress.

Rationale: Stress is a major risk factor for the development of depression. However, the underlying molecular mechanisms of stress vulnerability in depression are largely uncharacterized. Methods: P2X2 receptors (a major receptor for gliotransmitter-ATP) in the medial prefrontal cortex (mPFC) were identified by real-time qPCR, western blots and RNAscope in situ hybridization in chronic social defeat stress model (CSDS). We generated P2X2 conditional knockout mice and overexpressed AAV-P2X2 in CamkIIα-Cre mice. The depression-like behaviors were assessed via CSDS, subthreshold social defeat stress (SSDS), social interaction test (SI), forced interaction test (FIT), forced swimming test (FST), sucrose preference test (SPT), novel stressed feeding (NSF) and open field test (OFT). The neuronal activity and synapse function of P2X2 receptors in the mPFC were detected by in vivo fiber-photometry, patch-clamp techniques and neuronal morphometric analysis. Results: We identified that P2X2 receptors were increased in the mPFC of susceptible mice in CSDS. Conditional knockout of P2X2 receptors in pyramidal neurons promoted resilience of chronic stress-induced depressive-like behaviors, whereas pyramidal neurons - specific gain of P2X2 in the mPFC increased vulnerability to depressive-like behaviors. In vivo fiber-photometry, electrophysiology and neuronal morphometric analysis showed P2X2 receptors regulated neuronal activity and synapse function in the mPFC. Conclusions: Overall, our studies reveal a critical role of P2X2 in mediating vulnerability to chronic stress and identify P2X2 as a potential therapeutic target for treatment of stress-related mood disorders.

Physi-chemical mechanism and control effect of CaO2 inhibiting phosphorus release from sediments under different dosing modes.

CaO2 is known as an outstanding restoration agent to control phosphorus (P) release from sediments, and its mechanism is believed to depend on chemical passivation. However, we found that the physical actions might also be involved in inhibiting endogenous P release induced by CaO2. To further explore the mechanism of CaO2 controlling P release and optimize the dosing method, a 94-day incubation experiment was conducted under different CaO2 dosing modes. The results showed that CaO2 could form a dense passivation layer near its dosing position by reducing the median diameter of sediments, thereby inhibiting P release through physical obstruction. At the same time, the increase in the specific surface area and Ca content of sediments induced by CaO2 could synchronously enhance the physical and chemical adsorption properties of sediments to P. In addition, CaO2 could significantly reduce the P concentration in sediment interstitial water and the mobile-P and BAP contents in sediments through chemical oxidation and chemical precipitation. Under the combined actions of physical obstruction, physi-chemical adsorption, chemical oxidation, and chemical precipitation, CaO2 effectively inhibited endogenous P release. Finally, the P release flux in each reactor showed that multiple coverage and shallow injection had the optimal effect on inhibiting P release, and the former is recommended for the water systems with shallow sediments, and the latter is suitable for the water systems with deep sediments. In general, this experiment proposed the physi-chemical mechanism of P immobilization mediated by CaO2, studied the formation characteristics of the passivation layer, and optimized the dosing mode, which can provide valuable reference for the research and application of CaO2 controlling P release.

Coumarin thiazoles as unique structural skeleton of potential antimicrobial agents.

A novel type of coumarin thiazoles as unique multi-targeting antimicrobial agents were developed through four steps including cyclization, nucleophilic substitution and condensation starting from commercial resorcine. Most of the prepared coumarin thiazoles displayed favorable inhibitory potency against the tested strains. Noticeably, methyl oxime V-a exerted potent inhibitory efficacy against methicillin-resistant Staphylococcus aureus (MRSA) at low concentration (1 µg/mL) and showed broad antimicrobial spectrum. Medicinal bioevaluations revealed that the active molecule V-a exhibited low toxicity toward mammalian cells, rapidly killing effect, good capability of eradicating MRSA biofilms and unobvious probability to engender drug resistance. Chemical biological methods were employed to investigate preliminary mechanism, which indicated that compound V-a was able to damage the integrity of membrane to trigger leakage of protein, insert into MRSA DNA to block its replication and induce the generation of reactive oxygen species (ROS) to inhibit bacterial growth. Computational study manifested that low HOMO-LUMO energy gap of molecule V-a was favorable to exert high antimicrobial activity.