Endogenous Release Research Articles

Mechanistic Role of Methanolic Extract of Taraxacum officinale Roots as Cardioprotective Against Ischemia-Reperfusion Injury-Induced Myocardial Infarction in Rats.

Taraxacum officinale play an important role in the prophylaxis and treatment of cardiovascular disease (CVD). Taraxacum officinale is proven as promising antioxidant in earlier studies and one of its constituent "cichoric acid" is shown to have vasorelaxant property. Therefore, present study mainly designed to investigate the cardioprotective effects of Taraxacum officinale against ischemia-reperfusion injury (I/R injury)-induced myocardial dysfunction in rats. This study not only explored the overall cardioprotective potential but also tried to explore its molecular mechanism using pharmacological inhibition via L-NAME and glibenclamide. Pretreatment of methanolic extract of Taraxacum officinale significantly attenuated (p < 0.001) increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), infarct size, and thiobarbituric acid reactive substance (TBARS), while it increased the reduced levels of protein content, glutathione (GSH), and catalase (CAT) activity. Results showed that pretreatment with methanolic extract of Taraxacum officinale provides cardioprotection against I/R induced myocardial dysfunction, at least, may be mediated through the endogenous release of nitric oxide.

Detection of endogenous NPY release determined by novel GRAB sensor in cultured cortical neurons.

Neuropeptide Y (NPY) is an abundantly expressed peptide in the nervous system. Its widespread distribution along with its receptors, both centrally and peripherally, indicates its broad functions in numerous biological processes. However, the low endogenous concentration and diffuse distribution of NPY make it challenging to study its actions and dynamics directly and comprehensively. Studies on the role of NPY have primarily been limited to exogenous application, transgene expression, or knock-out in biological systems, which are often combined with pharmacological probes to delineate the involvement of specific NPY receptors. Therefore, to better understand the function of NPY in time and space, direct visualization of the real-time dynamics of endogenous NPY is a valuable and desired tool. Using the first-generation and newly developed intensiometric green fluorescent G-protein-coupled NPY sensor (GRAB NPY1.0), we, for the first time, demonstrate and characterize the direct detection of endogenously released NPY in cultured cortical neurons. A dose-dependent fluorescent signal was observed upon exogenous NPY application in nearly all recorded neurons. Pharmacologically evoked neuronal activity induced a significant increase in fluorescent signal in 32% of neurons, reflecting the release of NPY, despite only 3% of all neurons containing NPY. The remaining pool of neurons expressing the sensor were either non-responsive or displayed a notable decline in the fluorescent signal. Such decline in fluorescent signal was not rescued in cortical cultures transduced with an NPY overexpression vector, where 88% of the neurons were NPY-positive. Overexpression of NPY did, however, result in sensor signals that were more readily distinguishable. This may suggest that biological factors, such as subtle changes in intracellular pH, could interfere with the fluorescent signal, and thereby underestimate the release of endogenous NPY when using this new sensor in its present configuration. However, the development of next-generation NPY GRAB sensor technology is expected soon, and will eventually enable much-wanted studies on endogenous NPY release dynamics in both cultured and intact biological systems.

The Relationship Between Oxytocin and Alcohol Dependence.

The hypothalamic neuropeptide oxytocin (OT) is well known for its prosocial, anxiolytic, and ameliorating effects on various psychiatric conditions, including alcohol use disorder (AUD). In this chapter, we will first introduce the basic neurophysiology of the OT system and its interaction with other neuromodulatory and neurotransmitter systems in the brain. Next, we provide an overview over the current state of research examining the effects of acute and chronic alcohol exposure on the OT system as well as the effects of OT system manipulation on alcohol-related behaviors in rodents and humans. In rodent models of AUD, OT has been repeatedly shown to reduce ethanol consumption, particularly in models of acute alcohol exposure. In humans however, the results of OT administration on alcohol-related behaviors are promising but not yet conclusive. Therefore, we further discuss several physiological and methodological limitations to the effective application of OT in the clinic and how they may be mitigated by the application of synthetic OT receptor (OTR) agonists. Finally, we discuss the potential efficacy of cutting-edge pharmacology and gene therapies designed to specifically enhance endogenous OT release and thereby rescue deficient expression of OT in the brains of patients with severe forms of AUD and other incurable mental disorders.

Tailoring of bimetallic organic framework-polymeric film composites: Real-time fouling-free electrocatalytic application of hydrogen sulfide releasing from organic donors and live cells

Electrochemical real-time hydrogen sulfide (H2S) sensor in biological and chemical environments are great interest due to their impact of interferences and electrode-fouling effects. Hence, fouling-free detection of H2S is a key challenging to explore an unmasked electrocatalytic activity. In this context, a simple and robust strategy was developed based on bimetallic Ni-Co-MOF with poly(3,4-ethylenedioxythiophene) (PEDOTs) and poly(o-phenylenediamine) (PoPDA). The hybrid composite system exhibits tunable-structural morphology, cohesive electrical conductivity, strong interfacial chemical bonding and good anti-fouling property. The PEDOTs@Ni-Co-MOF/GCE yielded an enhanced catalytic performance with a concentration range of 1 nM to 250 µM, low detection limit of 0.186 nM, and high sensitivity (7.29 μA μM−1 cm−2). The water soluble GYY4137, and phosphordithioates-based donors were achieved dynamically quantify the real-time release of H2S against pH and co-incubation time (0–30 min). Additionally, bimetallic-MOF with the polymeric film platform achieved highly selective in other sulfur-containing complex medium and biomolecules due to its strong electrostatic net-charges and size exclusivity. A practical application was demonstrated in whole blood and biofluids with acceptable recoveries from 97.40 to 98.79 % (n = 3). The real-time endogenous release of H2S was evaluated in live cells (E. coli MG1655) by using a cysteine stimulator.

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia.

Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms underlying neurostimulation-induced pain relief. Here, we discuss the most commonly used neurostimulation techniques for treating chronic pain. We present evidence that neurostimulation-induced analgesia is in part driven by the release of endogenous opioids and that this endogenous opioid release is a common endpoint between different methods of neurostimulation. Finally, we introduce technological and clinical innovations that are being explored to optimize neurostimulation techniques for the treatment of pain, including multidisciplinary efforts between neuroscience research and clinical treatment that may refine the efficacy of neurostimulation based on its underlying mechanisms.

Effective adjuvantation of nanograms of influenza vaccine and induction of cross-protective immunity by physical radiofrequency adjuvant.

Novel adjuvants are highly demanded to aid in development of improved or new vaccines against existing or emerging infectious diseases. Considering commonly used Alum and MF59 adjuvants induce tissue stress and release of endogenous danger signals to mediate their adjuvant effects, physical modalities may be used to induce tissue stress and endogenous danger signal release to enhance vaccine-induced immune responses. Furthermore, physical adjuvants are less likely to induce significant systemic adverse reactions due to their localized effects. Recently we found non-invasive radiofrequency (RF) pretreatment of the skin could significantly enhance intradermal vaccine-induced immune responses in murine models that included pandemic influenza vaccine, pre-pandemic vaccine, and influenza internal antigen vaccine. It remained to be explored whether the physical RF adjuvant (RFA) could be used to boost seasonal influenza vaccination, spare vaccine doses, and induce cross-protective immunity. This study found the physical RFA could significantly enhance seasonal influenza vaccine-induced immune responses against each viral strain and robustly enhance low-dose (nanograms) H3N2 vaccine-induced immune responses and protection in murine models. RFA also induced cross-protective immunity against heterologous and heterosubtypic influenza viruses. Further studies found heat shock protein 70 (inducible endogenous danger signal) and myeloid differentiation primary response 88 adaptor played a crucial role in dose-sparing effects of RFA. These data strongly support further development of the physical RFA to boost influenza vaccination.

Next generation genetically encoded fluorescent sensors for serotonin

We developed a family of genetically encoded serotonin (5-HT) sensors (sDarken) on the basis of the native 5-HT1A receptor and circularly permuted GFP. sDarken 5-HT sensors are bright in the unbound state and diminish their fluorescence upon binding of 5-HT. Sensor variants with different affinities for serotonin were engineered to increase the versatility in imaging of serotonin dynamics. Experiments in vitro and in vivo showed the feasibility of imaging serotonin dynamics with high temporal and spatial resolution. As demonstrated here, the designed sensors show excellent membrane expression, have high specificity and a superior signal-to-noise ratio, detect the endogenous release of serotonin and are suitable for two-photon in vivo imaging.

Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience

Psychosis in disorders like schizophrenia is commonly associated with aberrant salience and elevated striatal dopamine. However, the underlying cause(s) of this hyper-dopaminergic state remain elusive. Various lines of evidence point to glutamatergic dysfunction and impairments in synaptic plasticity in the etiology of schizophrenia, including deficits associated with the GluA1 AMPAR subunit. GluA1 knockout (Gria1−/−) mice provide a model of impaired synaptic plasticity in schizophrenia and exhibit a selective deficit in a form of short-term memory which underlies short-term habituation. As such, these mice are unable to reduce attention to recently presented stimuli. In this study we used fast-scan cyclic voltammetry to measure phasic dopamine responses in the nucleus accumbens of Gria1−/− mice to determine whether this behavioral phenotype might be a key driver of a hyper-dopaminergic state. There was no effect of GluA1 deletion on electrically-evoked dopamine responses in anaesthetized mice, demonstrating normal endogenous release properties of dopamine neurons in Gria1−/− mice. Furthermore, dopamine signals were initially similar in Gria1−/− mice compared to controls in response to both sucrose rewards and neutral light stimuli. They were also equally sensitive to changes in the magnitude of delivered rewards. In contrast, however, these stimulus-evoked dopamine signals failed to habituate with repeated presentations in Gria1−/− mice, resulting in a task-relevant, hyper-dopaminergic phenotype. Thus, here we show that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may be an important contributor to aberrant salience and psychosis in psychiatric disorders like schizophrenia.

Practically Defined Off-State Dyskinesia Following Repeated Intraputamenal Glial Cell Line-Derived Neurotrophic Factor Administration.

We recently showed that by employing an enhanced drug-delivery approach, repeated administration of glial cell line-derived neurotrophic factor (GDNF) can produce a spatially distributed increased 18 F-DOPA positron emission tomography (PET) uptake, suggesting sprouting of dopaminergic terminals throughout the putamen structure. Despite this, we failed to prove a significant measurable clinical response. Since, however, we have identified a subject demonstrating a temporal relationship between repeated GDNF infusions and dyskinesia arising in the practically defined off (pracoff) state. To describe the development of pracoff dyskinesia across our study population and consider its utility as an indicator that trophic factor-induced terminal sprouting can affect enhanced endogenous dopamine levels. This was a blinded retrospective analysis of videotaped motor assessments at eight weekly study visits. Dyskinesia in the pracoff and supramaximal on state were rated using the Clinical Dyskinesia Rating Scale. Logistic regression was employed to explore the predictors of pracoff dyskinesia. Generalized estimated equations were used to estimate the cumulative effect of repeated GDNF infusions. Mild-moderate choreiform dyskinesia in the pracoff state were seen in 47 assessments in 17 (n=41) subjects. During the 18-month timeframe, each subsequent 8-week period of receiving GDNF increased the risk of demonstrating pracoff state dyskinesia by 34% (odds ratio [OR], 1.34 (95% confidence interval [CI], 1.20, 1.50); P< 0.001). An increasing supramaximal on dyskinesia score (OR, 1.17 [95% CI, 1.07, 1.30]; P= 0.001) also increased the likelihood of pracoff dyskinesia at that visit. We report the first description of increasingly prevalent pracoff-state dyskinesia developing during the course of a trophic factor study. This may provide a surrogate marker that GDNF can enable recovery of endogenous dopamine release even in advanced Parkinson's disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

Amino acids as indicators of seasonal variations in organic matter degradation in surface sediments from a shallow lake

Degradation of organic matter (OM) in sediments is a key link in nutrient cycling and sedimentation processes in lakes. The aim of this study was to explore the degradation of OM in surface sediments of a shallow lake (Baiyangdian Lake, China) under seasonal temperature variations. For this, we used the amino acid-based degradation index (DI) and the spatiotemporal distribution characteristics and sources of OM. Sediment OM in the lake mainly originated from freshwater aquatic plants and terrestrial C4 plants. The sediment at some sampling sites was affected by surrounding crops. The organic carbon and total nitrogen contents, and the total hydrolyzed amino acid concentrations in the sediments were highest in summer and lowest in winter. The lowest DI occurred in spring, which indicated that the OM in the surface sediment at this time was highly degraded and relatively stable, and the highest DI occurred in winter, which showed that the sediment was fresh. The water temperature was positively correlated with the organic carbon content (p < 0.01) and total hydrolyzed amino acids concentration (p < 0.05). Seasonal variations in the overlying water temperature had a large effect on OM degradation in the lake sediments. Our results will facilitate the management and restoration of lake sediments that suffer from endogenous release of OM in a warming climate.

Impact of Glucocorticoids on Cardiovascular System—The Yin Yang Effect

Glucocorticoids are not only endogenous hormones but are also administered exogenously as an anti-inflammatory and immunosuppressant for their long-term beneficial and lifesaving effects. Because of their potent anti-inflammatory property and ability to curb the cytokines, they are administered as lifesaving steroids. This property is not only made use of in the cardiovascular system but also in other major organ systems and networks. There is a fine line between their use as a protective anti-inflammatory and a steroid that could cause overuse-induced complications in major organ systems including the cardiovascular system. Studies conducted in the cardiovascular system demonstrate that glucocorticoids are required for growth and development and also for offering protection against inflammatory signals. Excess or long-term glucocorticoid administration could alter cardiac metabolism and health. The endogenous dysregulated state due to excess endogenous glucocorticoid release from the adrenals as seen with Cushing's syndrome or excess exogenous glucocorticoid administration leading to Cushing's-like condition show a similar impact on the cardiovascular system. This review highlights the importance of maintaining a glucocorticoid balance whether it is endogenous and exogenous in regulating cardiovascular health.

Strengthen the purification of eutrophic water and improve the characteristics of sediment by functional ecological floating bed suspended calcium peroxide and sponge iron jointly

To overcome the shortcomings of conventional ecological floating bed (CEFB) in purifying landscape water, this study constructed a functional ecological floating bed (FEFB) through the suspension of calcium peroxide (CP) and sponge iron (SI) jointly below the CEFB. The purification effect of water quality and influence of sediment were compared in control check, CEFB, and FEFB systems, which were loaded the same sediment and reclaimed water in a field experiment. Results showed that the FEFB suspended with CP and SI had evident purification effect on the quality of landscape water supplied with reclaimed water and can maintain stably the nutrient status of the water body at mesotrophic levels and low turbidity. The FEFB promoted the degradation of humus, thus eliminating the chroma risk in water body caused by the decay of plants from the CEFB. Moreover, the FEFB can control the sediment mass produced, reduce the total nitrogen (TN) mass of sediment, and decrease the transformable TN (TTN) content in the sediment. The FEFB enhanced the stability of phosphorus (P) in the sediment, where the relative content of Ca–P and stable P reached 42.18% and 64.27%, respectively. To sum up, the FEFB suspended with SI and CP can not only effectively control the eutrophication and sensory index of landscape water but also change the TTN content and P forms in sediment, making the sediment more stable. Thus, the FEFB provides an innovative approach to reduce endogenous nutrient release for landscape water along with recharging with reclaimed water.

Green Light Exposure Elicits Anti-inflammation, Endogenous Opioid Release and Dampens Synaptic Potentiation to Relieve Post-surgical Pain

Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents. However, its underlying mechanisms remain incompletely defined. In this study, we demonstrate that green light exposure reduced postsurgical hypersensitivity in rats. Moreover, this therapy potentiated the antinociceptive effects of morphine and ibuprofen on mechanical allodynia in male rats. Importantly, in female rats, GLED potentiated the antinociceptive effects of morphine but did not affect that of ibuprofen. We showed that green light increases endogenous opioid levels while lessening synaptic plasticity and neuroinflammation. Importantly, this study reveals new insights into how light exposure can affect neuroinflammation and plasticity in both genders. Clinical translation of these results could provide patients with improved pain control and decrease opioid consumption. Given the noninvasive nature of green light, this innovative therapy would be readily implementable in hospitals. PerspectiveThis study provides a potential additional therapy to decrease postsurgical pain. Given the safety, availability, and the efficacy of green light therapy, there is a significant potential for advancing the green light therapy to clinical trials and eventual translation to clinical settings.

The spatial distribution and characterization of phosphorus and nitrogen in a water-carrying lake: a case study of Lake Jiaogang, China.

The sources of P and N in water-carrying lakes include exogenous input and endogenous release. However, the influence of pollution from different sources on the dynamic distribution of N and P at the sediment-water interface in water-carrying lakes remains unclear. The objectives of this study were to investigate the differences in dynamic distribution characteristics of P compounds and N elements in Lake Jiaogang, a major water-carrying lake in eastern China. Four functional regions with different types of pollutant sources and different kinds of aquatic plants were selected to study the distribution of total P (TP), inorganic P, organic P, ammonium (NH4+-N), and nitrate (NO3--N). The results revealed that regions with internal-source pollutants contained the highest concentration of TP, Ca-P, and Fe-P with high concentrations. L-P, Al-P, mostly organic P, and soluble reactive phosphorous (SRP), the region with internal-source pollutants were lower than that with the imported-source pollutant. The concentration of dissolved NH4+-N showed high in regions with imported-source pollutants, however, in regions with internal-source pollutants, the dissolved NO3--N was with the highest concentration. Overall, P from upstream was still dominant in the sediments despite uptake by the aquatic plants. SRP showed high concentration in regions with imported-source pollutants due to the imported pollution and the improved bioavailability by plant root exudates. Feces and feed residues from aquatic livestock breeding resulted in the highest concentration of TN, NH4+-N, and dissolved NO3--N in the sediments of the region with internal-source pollutants. High concentrations of dissolved NH4+-N were due to the input of N from imported source pollutants. This study provides insights into the contributions of P and N to the eutrophication of the water-carrying lake.

Crotalphine Modulates Microglia M1/M2 Phenotypes and Induces Spinal Analgesia Mediated by Opioid-Cannabinoid Systems.

Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or induce undesirable effects. Crotalphine is a 14 amino acids synthetic peptide that induces a potent and long-lasting analgesic effect on acute and chronic pain models, peripherally mediated by the endogenous release of dynorphin A and the desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor. However, the effects of crotalphine on the central nervous system (CNS) and the signaling pathway have not been investigated. Thus, the central effect of crotalphine was evaluated on the partial sciatic nerve ligation (PSNL)-induced chronic neuropathic pain model. Crotalphine (100 µg/kg, p.o.)-induced analgesia on the 14th day after surgery lasting up to 24 h after administration. This effect was prevented by intrathecal administration of CB1 (AM251) or CB2 (AM630) cannabinoid receptor antagonists. Besides that, crotalphine-induced analgesia was reversed by CTOP, nor-BNI, and naltrindole, antagonists of mu, kappa, and delta-opioid receptors, respectively, and also by the specific antibodies for β-endorphin, dynorphin-A, and met-enkephalin. Likewise, the analgesic effect of crotalphine was blocked by the intrathecal administration of minocycline, an inhibitor of microglial activation and proliferation. Additionally, crotalphine decreased the PSNL-induced IL-6 release in the spinal cord. Importantly, in vitro, crotalphine inhibited LPS-induced CD86 expression and upregulated CD206 expression in BV-2 cells, demonstrating a polarization of microglial cells towards the M2 phenotype. These results demonstrated that crotalphine, besides activating opioid and cannabinoid analgesic systems, impairs central neuroinflammation, confirming the neuromodulatory mechanism involved in the crotalphine analgesic effect.

Indirect herbivore biomanipulation may halt regime shift from clear to turbid after macrophyte restoration

Eutrophication transforms clear water into turbid water in shallow lakes. Current restoration techniques focus on re-establishing the clear-water state rather than on its maintenance. We investigated the response of submerged macrophytes to temporary grass carp (Ctenopharyngodon idella) and scraping snail (Bellamya aeruginosa) introductions. We also explored the impacts of herbivores on underwater light conditions to identify their long- and short-term potential to halt regime shift from clear to turbid after clear-water state reestablishment. Herbivores reduced both the biomass of submerged macrophytes and accumulated nutrients in the tissue of submerged macrophytes. This potentially avoided the pulse of endogenous nutrient release which would have exceeded the threshold required for the regime shift from clear to turbid. However, herbivores had a non-significant impact on submerged macrophyte-reduced light attenuation coefficient, which has a positive linear relationship with water chlorophyll a. Further, grass carp and snails enhanced the inhibition ratio of submerged macrophytes to phytoplankton by 3.96 and 2.13 times, respectively. Our study provides novel findings on the potential of herbivore introduction as an indirect biomanipulation tool for halting the regime shift of shallow lakes from clear to turbid after the restoration of submerged macrophytes.

Investigation of the effect of free fatty acids on cell growth and Cytokine secretion

Interactions between immune and inflammatory cells are mediated primarily through the interaction of proteins, termed interleukins (IL) that are able to promote cell growth, differentiation as well as functional activation. TNF-α, IL-1 and IL-6 are the most important cytokines produced by monocytes. The aim of this study was to investigate the effect of docosahexaenoic acid (DAH), on immune cell proliferation along with cytokine production. This was tested using the THP-1 monocytic cell line, which in turn allowed observing how surface protein cytokine expression was affected by docosahexaenoic acid treatment and whether the effect of incubation would reduce the stimulus-induced production of pro-inflammatory cytokines. The experimental method employed Linked Immunosorbent Assays, while both Cell Titer 96® AQueous One Solution Cell Proliferation Assay and Titer 96 AQueous One Solution were used to determine cell proliferation. THP-1 cells induce growth-promoting activity and, the concentration of DHA toxic effect began at around 100 µM and reached maximum toxicity at around 200 µM. The results demonstrate that DHA inhibited endogenous IL-8 release when compared to a control group where the inhibition was maintained for 3 days. The study revealed the effect of docosahexaenoic acid (DHA), on immune cell proliferation and cytokine production.

Engineering mitochondrial uncoupler synergistic photodynamic nanoplatform to harness immunostimulatory pro-death autophagy/mitophagy

Generally, autophagy/mitophagy, as a highly conserved lysosomal-based catabolic pathway, compromises the photodynamic therapy (PDT) efficiency by increasing the adaptation of tumor cells toward reactive oxygen species (ROS)-triggered protein damages and mitochondrial destruction. On the other hand, excessively activated autophagy/mitophagy cascades can provoke autophagic cell death and promote the endogenous antigens release of dying cells, thus playing a vital role in initiating the antitumor immune responses. To harness the exquisite immunomodulating effect of pro-death autophagy/mitophagy, we rationally constructed a MnO2 shell-coated multifunctional porphyrinic metal–organic framework (MOF) to load carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The wrapped MnO2 shell could not only prevent premature release of CCCP during blood circulation but also conquer tumor hypoxia by catalyzing the decomposition of intratumoral H2O2. After entering tumor cells, the MnO2 shell could scavenge over-expressed glutathione (GSH), resulting in burst CCCP release and GSH-depletion/O2-generation enhanced PDT. More importantly, the released CCCP acts as a mitochondrial uncoupler can elicit mitochondrial depolarization and mitophagy, which could significantly boost the autophagy/mitophagy levels generated during PDT and consequently convert the pro-survival autophagy/mitophagy to pro-death, leading tumor cells to autophagic and immunogenic cell death. In vivo results reveal that the CCCP synergistic PDT could induce excessive immunostimulatory autophagy/mitophagy associated with T-cell responses and immunological memory, leading to complete ablation of primary tumors and prevention of tumor recurrence and lung metastasis. The effectiveness of this strategy may highlight the pro-death role and immunomodulating effect of autophagy/mitophagy in cancer therapy, providing a novel yet versatile avenue to enhance the efficacy of cancer treatments.

Effects of Seasonal Variation on Water Quality Parameters and Eutrophication in Lake Yangzong

Understanding the seasonal variation characteristics and trends in water quality is one of the most important aspects for protecting and conserving lakes. Lake Yangzong water quality parameters and nutrients, including water temperature, dissolved oxygen (DO), pH, conductivity, Chlorophyll-a, phycocyanin, total nitrogen (TN) and total phosphorus (TP), were monitored in different seasons from 2015 to 2021. Based on the monitoring data, the temporal and spatial variations of various parameters were analyzed. The results showed that Lake Yangzong is a warm monomictic lake. The Pearson correlation coefficient and correlation analysis showed water quality parameters were significantly correlated and probably affected by temperature. Cyanobacteria were at risk of blooming in spring and autumn. The contents of TN and TP in winter were significantly higher than in summer, especially TN, with both reaching a peak at the epilimnion and hypolimnion in December 2020 (TN = 1.3 mg/L, TP = 0.06 mg/L). We also observed a dual risk of endogenous release and exogenous input. Therefore, strengthening the supervision for controlling eutrophication caused by human activities and endogenous release is urgently needed.