Effects of Phasic Activation of Locus Ceruleus on Cortical Neural Activity and Auditory Discrimination Behavior.

Although the locus ceruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (LC-NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential and single-unit activity in multiple cortical regions associated with auditory-motor processing, including the auditory cortex, posterior parietal cortex, secondary motor cortex, anterior cingulate cortex, prefrontal cortex, and orbitofrontal cortex (OFC), in response to optogenetic activation (40 Hz and 0.5 s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillation (50-80 Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in norepinephrine levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a go/no-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

Cortical and thalamic modulation of auditory gating in the posterior parietal cortex of awake mice.

Auditory gating (AG) is an adaptive mechanism for filtering out redundant acoustic stimuli to protect the brain against information overload. AG deficits have been found in many mental illnesses, including schizophrenia (SZ). However, the neural correlates of AG remain poorly understood. Here, we found that the posterior parietal cortex (PPC) shows an intermediate level of AG in auditory thalamocortical circuits, with a laminar profile in which the strongest AG is in the granular layer. Furthermore, AG of the PPC was decreased and increased by optogenetic inactivation of the medial dorsal thalamic nucleus (MD) and auditory cortex (AC), respectively. Optogenetically activating the axons from the MD and AC drove neural activities in the PPC without an obvious AG. These results indicated that AG in the PPC is determined by the integrated signal streams from the MD and AC in a bottom-up manner. We also found that a mouse model of SZ (postnatal administration of noncompetitive N-methyl-d-aspartate receptor antagonist) presented an AG deficit in the PPC, which may be inherited from the dysfunction of MD. Together, our findings reveal a neural circuit underlying the generation of AG in the PPC and its involvement in the AG deficit of SZ.

The attenuating effects of serine against cadmium induced immunotoxicity through regulating M1/M2 and Th1/Th2 balance in spleen of C57BL/6 mice.

Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl2, 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.

Cadmium Induces Kidney Iron Deficiency and Chronic Kidney Injury by Interfering with the Iron Metabolism in Rats.

Cadmium (Cd) is a common environmental pollutant and occupational toxicant that seriously affects various mammalian organs, especially the kidney. Iron ion is an essential trace element in the body, and the disorder of iron metabolism is involved in the development of multiple pathological processes. An iron overload can induce a new type of cell death, defined as ferroptosis. However, whether iron metabolism is abnormal in Cd-induced nephrotoxicity and the role of ferroptosis in Cd-induced nephrotoxicity need to be further elucidated. Sprague Dawley male rats were randomly assigned into three groups: a control group, a 50 mg/L CdCl2-treated group, and a 75 mg/L CdCl2-treated group by drinking water for 1 month and 6 months, respectively. The results showed that Cd could induce renal histopathological abnormalities and dysfunction, disrupt the mitochondria's ultrastructure, and increase the ROS and MDA content. Next, Cd exposure caused GSH/GPX4 axis blockade, increased FTH1 and COX2 expression, decreased ACSL4 expression, and significantly decreased the iron content in proximal tubular cells or kidney tissues. Further study showed that the expression of iron absorption-related genes SLC11A2, CUBN, LRP2, SLC39A14, and SLC39A8 decreased in proximal tubular cells or kidneys after Cd exposure, while TFRC and iron export-related gene SLC40A1 did not change significantly. Moreover, Cd exposure increased SLC11A2 gene expression and decreased SLC40A1 gene expression in the duodenum. Finally, NAC or Fer-1 partially alleviated Cd-induced proximal tubular cell damage, while DFO and Erastin further aggravated Cd-induced cell damage. In conclusion, our results indicated that Cd could cause iron deficiency and chronic kidney injury by interfering with the iron metabolism rather than typical ferroptosis. Our findings suggest that an abnormal iron metabolism may contribute to Cd-induced nephrotoxicity, providing a novel approach to preventing kidney disease in clinical practice.

Anti-Inflammatory Effect of Xanthones from Hypericum beanii on Macrophage RAW 264.7 Cells through Reduced NO Production and TNF-α, IL-1ß, IL-6, and COX-2 Expression.

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2-24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 µM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy.

Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification.

BACKGROUND: Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. METHOD: Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. RESULT: The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. CONCLUSION: Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

BACKGROUND: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. RESULTS: Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. CONCLUSION: Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

Pristane induced lupus mice as a model for neuropsychiatric lupus (NPSLE).

BACKGROUND: The pristane-induced lupus (PIL) model is a useful tool for studying environmental-related systemic lupus erythematosus (SLE). However, neuropsychiatric manifestations in this model have not been investigated in detail. Because neuropsychiatric lupus (NPSLE) is an important complication of SLE, we investigated the neuropsychiatric symptoms in the PIL mouse model to evaluate its suitability for NPSLE studies. RESULTS: PIL mice showed olfactory dysfunction accompanied by an anxiety- and depression-like phenotype at month 2 or 4 after pristane injection. The levels of cytokines (IL-1ß, IFN-α, IFN-ß, IL-10, IFN-γ, IL-6, TNF-α and IL-17A) and chemokines (CCL2 and CXCL10) in the brain and blood-brain barrier (BBB) permeability increased significantly from week 2 or month 1, and persisted throughout the observed course of the disease. Notably, IgG deposition in the choroid plexus and lateral ventricle wall were observed at month 1 and both astrocytes and microglia were activated. Persistent activation of astrocytes was detected throughout the observed course of the disease, while microglial activation diminished dramatically at month 4. Lipofuscin deposition, a sign of neuronal damage, was detected in cortical and hippocampal neurons from month 4 to 8. CONCLUSION: PIL mice exhibit a series of characteristic behavioral deficits and pathological changes in the brain, and therefore might be suitable for investigating disease pathogenesis and for evaluating potential therapeutic targets for environmental-related NPSLE.

[Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy].

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

Molybdenum and cadmium co-exposure promotes M1 macrophage polarization through oxidative stress-mediated inflammatory response and induces pulmonary fibrosis in Shaoxing ducks (Anas platyrhyncha).

High molybdenum (Mo) and cadmium (Cd) are harmful to the body, but pulmonary toxicity induced by Mo and Cd co-exposure is unknown. To assess the combined impacts of Mo and Cd on fibrosis through M1 polarization in the lung of ducks, 80 healthy 8-day-old Shaoxing ducks (Anas platyrhyncha) were randomly assigned to 4 groups and fed with containing unequal doses of Mo or/and Cd diet. Lung tissues were collected on the 16th week. Results indicated that Mo or/and Cd significantly increased their contents in the lungs, and led to trace elements disorder and histological abnormality, and oxidative stress accompanied by promoting contents of H2 O2 and MDA and decreasing activities of T-SOD, GSH-Px, and CAT, then activated the TLR4/NF-κB/NLRP3 pathway accompanied by upregulating Caspase-1, ASC, IL-18, IL-1ß, TLR4, NF-κB, and NLRP3 expression levels, and disrupted M1/M2 balance to divert toward M1, which evoked the TGF-ß/Smad2/3-mediated fibrosis by elevating TGF-ß1, Smad2, Smad3, COL1A1, α-SMA, and MMP2 expression levels, and decreasing Smad7 and TIMP2 expression levels. The changes of the combined group were most obvious. To sum up, the research demonstrated that Mo or/and Cd may cause macrophages to polarize toward M1 by oxidative stress-mediated the TLR4/NF-κB/NLRP3 pathway, then result in fibrosis through the TGF-ß1/Smad2/3 pathway in duck lungs. Mo and Cd may worsen lung damage.

Nitrogen form-mediated ethylene signal regulates root-to-shoot K+ translocation via NRT1.5.

Nitrogen-potassium synergistic and antagonistic interactions are the typical case of nutrient interactions. However, the underlying mechanism for the integration of the external N form into K+ homeostasis remains unclear. Here, we show that opposite effects of NO3- and NH4+ on root-shoot K+ translocation were due to differential regulation of an ethylene signalling pathway targeting the NRT1.5 transporter. NH4+ upregulated the transcriptional activity of EIN3, but repressed the expression of NRT1.5. However, the addition of NO3- strongly suppressed the activity of EIN3, whereas its addition upregulated the expression of AtNRT1.5 and shoot K+ concentration. The 35S:EIN3/ein3eil1 plants, nrt1.5 mutants and nrt1.5/skor double mutants displayed a low K+ chlorosis phenotype, especially under NH4+ conditions with low K+ supply. Ion content analyses indicate that root-to-shoot K+ translocation was significantly reduced in these mutants. A Y1H assay, an EMSA and a transient expression assay confirmed that AtEIN3 protein could directly bind to the promoter of NRT1.5 to repress its expression. Furthermore, grafted plants with the roots of 35S:EIN3 and ein3eil1/nrt1.5 mutants displayed marked leaf chlorosis with a low K+ concentration. Collectively, our findings reveal that the interaction between N form and K+ was achieved by modulating root-derived ethylene signals to regulate root-to-shoot K+ translocation via NRT1.5.

Manganese accumulation and plant physiology behavior of Camellia oleifera in response to different levels of potassium fertilization.

The effects of potassium (K) fertilization (KCl, analytically pure; 0, 60, 200, and 400 mg kg-1) on the growth and Mn accumulation of Camellia oleifera in two types of Mn-contaminated soils were investigated. The potential mechanisms underlying the impacts of K fertilization were explored. C. oleifera accumulated high amounts of Mn in both soil conditions. The addition of K fertilizer decreased the soil pH and promoted Mn accumulation in C. oleifera. However, the plant biomass decreased significantly under the high level of K fertilization (400 mg kg-1), and the oxidative stress was stimulated under Mn contamination. But an appropriate concentration of K fertilizer (200 mg kg-1) was necessary for the formation of photosynthesis pigments, nonenzymatic antioxidants and antioxidant enzymes, metabolic processes, and nutrient uptake. Furthermore, when plants supplemented with a low level of K fertilization (200 mg kg-1), the catalase activity in C. oleifera leaves was enhanced to alleviate oxidative stress and protect the plant from Mn contamination. Our study demonstrated that 200 mg kg-1 of K fertilizer has the potential to further enhance the efficiency of Mn phytoremediation by C. oleifera.

[Expressions of pannexin proteins in I-10 Leydig tumor cells and TM3 Leydig cells and their regulatory effect on the channel function in mice].

OBJECTIVE: To investigate the expressions of the pannexin (Panx) proteins in I-10 Leydig tumor cells and TM3 Leydig cells and their regulatory effect on the Panx channel function in mice. METHODS: The expressions of the Panx-1 and Panx-2 proteins in the mouse Leydig tumor cells were determined by Western blot. The I-10 Leydig tumor cells were treated with carbenoxolone (CBX) at 100 µmol/L or probenecid (PBN) at 200 µmol/L, the fluorescence resonance energy transfer (FRET) detected by time-lapse fluorescence imaging, and the extracellular adenosine 5'-triphosphate (eATP) level measured with the commercial detection kit. Molecular biological methods were used to interfere with shRNA and overexpress mPanx-1 the Panx-1 gene and regulate the expression and function of the Panx-1 protein. RESULTS: The expressions of Panx-1 (ï¼»289.5 ± 55.8ï¼½%) and Panx-2 (ï¼»264.5 ± 24.6ï¼½%) were significantly increased in the I-10 Leydig tumor cells as compared with those in the normal TM3 Leydig cells (both P < 0.05). FRET was remarkably reduced after treated with CBX (ï¼»87.5 ± 17.7ï¼½%) and PBN (ï¼»89.3 ± 14.3ï¼½%) in comparison with that in the control group (both P < 0.01). At 8, 16 and 24 hours, the eATP level was decreased by (57.3 ± 7.2)%, (56.4 ± 9.6)% and (63.4 ± 6.4)% in the CBX group (P < 0.01) and (61.7 ± 2.5)%, (35.8 ± 1.6)% and (13.5 ± 8.3)% in the PBN group (P < 0.01). Molecular biological treatment down-regulated the expression of Panx-1 by (38.3 ± 5.2)% and (31.8 ± 5.1)% in the shRNA1 and shRNA2 groups, respectively (both P < 0.01), but up-regulated that of Panx-1 by (128.4 ± 7.5)% in the mPanx-1 group (P < 0.01) as compared with the negative control. FRET was reduced by (72.4 ± 39.4)% in the shRNA group (P < 0.01) and the eATP level by (14.7 ± 0.1)%, (13.7 ± 0.3)% and (13.1 ± 0.3)% at 8, 16 and 24 hours, respectively (P < 0.01) while FRET elevated by (122.5 ± 17.1)% in the mPanx-1 group (P < 0.01) and the eATP level by (886.1 ± 82.1)%, (885.8 ± 83.3)% and (841.5 ± 21.8)% at 8, 16 and 24 hours, respectively (P < 0.01). CONCLUSIONS: The expressions of Panx-1 and Panx-2 are increased in I-10 mouse Leydig tumor cells, and inhibiting the Panx channel with CBX, PBN and shRNA reduces FRET and the eATP level in the I-10 cells.

Utilization and transformation of Chrysotila dentata-derived dissolved organic matter by phycosphere bacteria Marinobacter hydrocarbonoclasticus and Bacillus firmus.

The dissolved organic matter (DOM) released from the cocoolithophores (Chrysotila dentata) was studied in laboratory experiments after co-culturing C. dentata with bacteria. Marinobacter hydrocarbonoclasticus (CA6)-γ-Proteobacteria and Bacillus firmus (CF2) were used to investigate the utilization and processing of the DOM derived from C. dentata, utilizing fluorescence excitation-emission matrix (EEM) combined with parallel factor analysis (EEM-PARAFAC), while measuring algal abundance and photosynthetic parameters. The experimental groups consisted of axenic C. dentata groups, filter cultured with bacteria (CA6 or CF2) groups, C. dentata co-cultured with bacteria (CA6 or CF2) groups and axenic bacteria (CA6 or CF2) groups. We then evaluated the processing of DOM by determining four fluorescence indices. The number of C. dentata cells and the photosynthetic capacity of microalgae were enhanced by CA6 and CF2. The main known fluorophores, including humic-like components and protein-like components, were present in all sample. The protein-like component of algal-bacterial co-cultures was effectively utilized by CA6 and CF2. The humic-like components increased at the end of the culture time for all cultures. Meanwhile, the average fluorescence intensity of protein-like in CA6 co-culture with algae was lower than that in CF2 co-culture with algae over time. On the other hand, the average fluorescence intensity of humic-like in CA6 was higher than CF2. However, the total change in fluorescence in humic-like and protein-like of axenic CF2 cultures was lower than that of CA6. Hence, the ability of CA6 to transform microalgal-derived DOM was superior to that of CF2, and CF2's ability to consume bacterial-derived DOM was superior to that of CA6.

Upgrading anode graphite from retired lithium ion batteries via solid-phase exfoliation by mechanochemical strategy.

Vast quantities of anode graphite from waste lithium ion batteries (LIBs), as a type of underrated urban mine, has enormous potential to be exploited for resource recovery. Herein, we propose a benign process integrating low-temperature pyrolysis and mechanochemical techniques to upcycle spent graphite (SG) from end-of-life LIBs. Pyrolysis at 500 °C leads to about 82.2 % PVDF dissociation in thermal treated graphite (TG). Solid-phase exfoliation via ball milling assisted by urea successfully produces abundant graphite flakes and a small amount of monolayer graphene nanosheet at the edge of mechanochemically processed graphite (MG). Subsequent rinsing removes the residual LiF salts. High purity and unique edge structural features of the as-prepared MG offer more active sites and storage reservoir for intercalation and de-intercalation of lithium ions, resulting in enhanced lithium-ion diffusion kinetics, excellent reversible specific capacity and desirable rate capability. Inspiringly, MG exhibits a remarkably enhanced initial specific charge capacity of 521.3 mAh g-1 during the first charge-discharge, and only declines from 569.9 mAh g-1 to 538 mAh g-1 with slight attenuation after 50 consecutive cycles at 0.1 A/g, indicating satisfactory cycle stability. Additionally, the purification and reconstruction mechanism for MG have been illustrated in detail. This study offers a green strategy to reconstruct and upgrade anode graphite from LIBs, which can realize sustainable waste management.

Cytotoxic and anti-inflammatory constituents from roots of Hypericum beanii and the antitumor potential under the view of cancer-related inflammation.

Hypericum beanii, a traditional folk medicine plant, has been employed in the treatment of various inflammation-related diseases and has demonstrated promising potential as an herbal remedy for cancer. In this study, we isolated 29 compounds from the roots of H. beanii. We evaluated their cytotoxic effects on five human cancer cell lines, which revealed that the ethanol extract, along with compounds 4 and 14, exhibited significant cytotoxic activity. Additionally, we assessed their anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Our findings showed that the ethanol extract (IC50 = 7.41 ± 0.38 µg/mL), compound 4 (IC50 = 7.82 ± 0.42 µM), and compound 14 (IC50 = 3.05 ± 0.06 µM) displayed substantial anti-inflammatory activity. ELISA assays and qPCR analysis revealed that compounds 4 and 14 may exert their anti-inflammatory and antitumor effects by inhibiting the expression of iNOS, TNF-α, IL-1ß, and IL-6 mRNA, shedding light on their role in cancer-related inflammation.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.

The research progress of crosstalk mechanism of autophagy and apoptosis in diabetic vascular endothelial injury.

In recent years, the widespread prevalence of diabetes has become a major killer that threatens the health of people worldwide. Of particular concern is hyperglycemia-induced vascular endothelial injury, which is one of the factors that aggravate diabetic vascular disease. During the process of diabetic vascular endothelial injury, apoptosis is an important pathological manifestation and autophagy is a key regulatory mechanism. Autophagy and apoptosis interact with each other. Hence, the crosstalk mechanism between the two processes is an important means of regulating diabetic vascular endothelial injury. This article reviews the research progress in apoptosis in the context of diabetic vascular endothelial injury and discusses the crosstalk mechanism of autophagy and apoptosis and its role in this injury. The purpose is to guide the prevention and treatment of diabetic vascular endothelial injury in the future.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.