Morphine Induced Neuroprotection in Ischemic Stroke by Activating Autophagy Via mTOR-Independent Activation of the JNK1/2 Pathway.

Morphine (Mor) has exhibited efficacy in safeguarding neurons against ischemic injuries by simulating ischemic/hypoxic preconditioning (I/HPC). Concurrently, autophagy plays a pivotal role in neuronal survival during IPC against ischemic stroke. However, the involvement of autophagy in Mor-induced neuroprotection and the potential mechanisms remain elusive. Our experiments further confirmed the effect of Mor in cellular and animal models of ischemic stroke and explored its potential mechanism. The findings revealed that Mor enhanced cell viability in a dose-dependent manner by augmenting autophagy levels and autophagic flux in neurons subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Pretreatment of Mor improved neurological outcome and reduced infarct size in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) at 1, 7 and 14 days. Moreover, the use of autophagy inhibitors nullified the protective effects of Mor, leading to reactive oxygen species (ROS) accumulation, increased loss of mitochondrial membrane potential (MMP) and neuronal apoptosis in OGD/R neurons. Results further demonstrated that Mor-induced autophagy activation was regulated by mTOR-independent activation of the c-Jun NH2- terminal kinase (JNK)1/2 Pathway, both in vitro and in vivo. Overall, these findings suggested Mor-induced neuroprotection by activating autophagy, which were regulated by JNK1/2 pathway in ischemic stroke.

Morphine Preconditioning Alleviates Ischemia/Reperfusion-induced Caspase-8-dependent Neuronal Apoptosis through cPKCγ-NF-κB-cFLIPL Pathway.

BACKGROUND: Perioperative cerebral ischemia/reperfusion injury is a major contributor to postoperative death and cognitive dysfunction in patients. It was reported that morphine preconditioning (MP) can mimic ischemia/hypoxia preconditioning to protect against ischemia/reperfusion injury. However, the mechanism of MP on the ischemia/reperfusion-induced neuronal apoptosis has not been fully clarified. METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model of mice and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary cortical neurons were used to mimic ischemic stroke. In vivo, the infarct size was measured by using TTC staining; NDSS, Longa score system, and beam balance test were performed to evaluate the neurological deficits of mice; the expression of the protein was detected by using a western blot. In vitro, the viability of neurons was determined by using CCK-8 assay; the expression of protein and mRNA were assessed by using western blot, RT-qPCR, and immunofluorescent staining; the level of apoptosis was detected by using TUNEL staining. RESULTS: MP can improve the neurological functions of mice following MCAO/R (P<0.001, n=10 per group). MP can decrease the infarct size (P<0.001, n=10 per group) and the level of cleaved-caspase-3 of mice following MCAO/R (P<0.01 or 0.001, n=6 per group). MP can increase the levels of cPKCγ membrane translocation, p-p65, and cFLIPL, and decrease the levels of cleaved-caspase-8, 3 in neurons after OGD/R or MCAO/R 1 d (P<0.05, 0.01 or 0.001, n=6 per group). In addition, MP could alleviate OGD/R-induced cell apoptosis (P<0.001, n=6 per group). CONCLUSION: MP alleviates ischemia/reperfusion-induced Caspase 8-dependent neuronal apoptosis through the cPKCγ-NF-κB-cFLIPL pathway.

Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Mouse serum albumin induces neuronal apoptosis and tauopathies.

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Astrocytes Excessively Engulf Synapses in a Mouse Model of Alzheimer's Disease.

Synapse loss is one of the most critical features in Alzheimer's disease (AD) and correlates with cognitive decline. Astrocytes mediate synapse elimination through multiple EGF-like domains 10 (MEGF10) pathways in the developing and adult brain to build the precise neural connectivity. However, whether and how astrocytes mediate synapse loss in AD remains unknown. We here find that the phagocytic receptor MEGF10 of astrocytes is significantly increased in vivo and in vitro, which results in excessive engulfment of synapses by astrocytes in APP/PS1 mice. We also observe that the astrocytic lysosomal-associated membrane protein 1 (LAMP1) is significantly elevated, colocalized with the engulfed synaptic puncta in APP/PS1 mice, and astrocytic lysosomes contain more engulfed synaptic puncta in APP/PS1 mice relative to wild type mice. Together, our data provide evidence that astrocytes excessively engulf synapses in APP/PS1 mice, which is mediated by increased MEGF10 and activated lysosomes. The approach targeting synapse engulfment pathway in astrocytes would be a potent therapy for AD.

Density affects plant size in the Gobi Desert.

Plant size is a crucial functional trait with substantial implications in agronomy and forestry. Understanding the factors influencing plant size is essential for ecosystem management and restoration efforts. Various environmental factors and plant density play significant roles in plant size. However, how plant size responds to mean annual precipitation (MAP), mean annual temperature (MAT), and density in the arid areas remains incomplete. To address this knowledge gap, we conducted comprehensive vegetation surveys in the Gobi Desert in northwestern China with a MAP below 250 mm. We also collected climate data to disentangle the respective influences of climate and density on the community-weighted plant height, crown length, and crown width. Our observations revealed that the community-weighted mean plant height, crown length, and width demonstrated a positive association with MAT but negative relationships with both MAP and density. These patterns can be attributed to the predominance of shrubs over herbs in arid regions, as shrubs tend to be larger in size. The proportion of shrubs increases with MAT, while it decreases with MAP and density, resulting in higher plant height and larger crown dimensions. Although both MAP and MAT affect plant size in the Gobi Desert, our findings highlight the stronger role of plant density in regulating plant size, indicating that the surrounding plant community and competition among individuals are crucial drivers of plant size patterns. Our findings provide valuable guidance for nature-based solutions for vegetation restoration and ecosystem management, highlighting the importance of considering plant density as a key factor when designing and implementing restoration strategies in arid areas.

Leaf-Root-Soil Stoichiometric Characteristics in Different Shrub Ages of Ammopiptanthus mongolicus.

The ecological indicators for the growth and restoration of A. mongolicus populations are important for grasping the regulatory mechanisms of the biogeochemistry cycle, and for providing basic data for the prediction and evaluation of the evolution characteristics of natural A. mongolicus populations. We conducted studies on the eco-stoichiometric characteristics of natural A. mongolicus in different shrub ages, in order to understand the nutrient limitations for the growth and development of A. mongolicus and the synergy between the soil, leaves and roots, and to explore the C, N and P stoichiometric characteristics on A. mongolicus. The results showed the following: (1) The response of C, N and P stoichiometric characteristics in the leaves, roots and soil to changes in shrub age was not completely consistent. The leaf C content was young shrub> mature shrub> middle age shrub. The C content in the root system and C and N content in the soil showed an upward trend with increasing shrub age. The N and P contents of the root system and the P content of the soil showed a downward trend with increasing shrub age. The stoichiometric ratios C:N, C:P and N:P in the leaves, roots and soil showed an upward trend, and the N:P ratios in the leaves and roots were similar. (2) Among the stoichiometric characteristics of the leaves, C, N and P, leaves P and C:P are the most sensitive to shrub age changes, and have ecological implications for the growth and population dynamics of A. mongolicus. The average N:P ratios of young A. mongolicus leaves in young, middle-aged and mature shrubs were 15.32, 18.23 and 21.76, respectively. It can be seen that with an increase in shrub age, the growth of A. mongolicus gradually shifted from being jointly restricted by N and P to being more restricted by P. (3) The N content and the C∶N and N∶P ratios of A. mongolicus are classified as "strictly homoeostasis ", which shows strong plant homoeostasis for environmental adaptability. The N supplemented by symbiotic nitrogen fixation makes A. mongolicus have strong N internal homoeostasis. Therefore, in a desert grassland with low N content, the growth process of A. mongolicus may be easily restricted by P due to the additional N absorbed by it. (4) The C, N and P contents of the leaves, roots and soils of the three shrubs were shown as leaf > root > soil, and the difference was significant (p < 0.05). The correlation analysis showed that the C, N and P contents of the soil, roots and leaves and their stoichiometric ratio characteristics of the three shrubs showed a certain correlation. Among them, the P content of the soil was significantly related to the N:P ratio of the leaves and roots. Therefore, P is likely to become a limiting factor in the plant growth and repair process of the plant ecosystem in the A. mongolicus population. In summary, during the growth of A. mongolicus, special attention should be paid to the balance of nutrients. In order to improve its productivity, it is recommended to reasonably apply P fertilizers in the process of tending management to enhance the soil nutrient status and improve plant nutrient utilization efficiency and homoeostasis.

The unique interplay of mitochondrial oxidative phosphorylation (OXPHOS) and immunity and its potential implication for the sex- and age-related morbidity of severe COVID-19 patients.

Aged male patients are more vulnerable to severe or critical symptoms of COVID-19, but the underlying mechanism remains elusive. In this study, we analyzed previously published scRNA-seq data from a large cohort of COVID-19 patients, castrated and regenerated mice, and bulk RNA-seq of a RNAi library of 400 genes, and revealed that both immunity and OXPHOS displayed cell-type-, sex-, and age-related variation in the severe or critical COVID-19 patients during disease progression, with a more prominent increase in immunity and decrease in OXPHOS in myeloid cells in the males relative to the females (60-69 years old). Male severe or critical patients above 70 years old were an exception in that the compromised negative correlation between OXPHOS and immunity in these patients was associated with its disordered transcriptional regulation. Finally, the expression levels of OXPHOS and androgens were revealed to be positively correlated, and the responses of macrophages to android fluctuation were more striking than other types of detected immune cells in the castrated mice model. Therefore, the interplay of OXPHOS and immunity displayed a cell-type-specific, age-related, and sex-biased pattern, and the underlying potential regulatory role of the hormonal milieu should not be neglected.

Droplet magnetic-controlled microfluidic chip integrated nucleic acid extraction and amplification for the detection of pathogens and tumor mutation sites.

Traditional nucleic acid extraction and detection is based on open operation, which may cause cross-contamination and aerosol formation. This study developed a droplet magnetic-controlled microfluidic chip integrated nucleic acid extraction, purification and amplification. The reagent is sealed in oil to form a droplet, and the nucleic acid is extracted and purified by controlling the movement of the magnetic beads (MBs) through a permanent magnet, ensuring a closed environment. This chip can automatically extract nucleic acid from multiple samples within 20 min, and can be directly placed in the in situ amplification instrument for amplification without further transfer of nucleic acid, characterized by simple, fast, time-saving and labor-saving. The results showed that the chip was able to detect <10 copies/test SARS-CoV-2 RNA, and EGFR exon 21 L858R mutations were detected in H1975 cells as low as 4 cells. In addition, on the basis of the droplet magnetic-controlled microfluidic chip, we further developed a multi-target detection chip, which used MBs to divide the nucleic acid of the sample into three parts. And the macrolides resistance mutations A2063G and A2064G, and the P1 gene of mycoplasma pneumoniae (MP) were successfully detected in clinical samples by the multi-target detection chip, providing the possibility for future application in the detection of multiple pathogens.

Magnetic Bead Manipulation in Microfluidic Chips for Biological Application.

Magnetic beads manipulation in microfluidic chips is a promising research field for biological application, especially in the detection of biological targets. In this review, we intend to present a thorough and in-depth overview of recent magnetic beads manipulation in microfluidic chips and its biological application. First, we introduce the mechanism of magnetic manipulation in microfluidic chip, including force analysis, particle properties, and surface modification. Then, we compare some existing methods of magnetic manipulation in microfluidic chip and list their biological application. Besides, the suggestions and outlook for future developments in the magnetic manipulation system are also discussed and summarized.

ArhGAP11A mediates amyloid-ß generation and neuropathology in an Alzheimer's disease-like mouse model.

Amyloid-ß (Aß) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Aß generation and Aß oligomer (Aßo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aß generation by decreasing the expression of APP, PS1, and ß-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aßo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aß production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aßos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment.

On-Chip Nucleic Acid Purification Followed by ddPCR for SARS-CoV-2 Detection.

We developed a microfluidic chip integrated with nucleic acid purification and droplet-based digital polymerase chain reaction (ddPCR) modules to realize a 'sample-in, result-out' infectious virus diagnosis. The whole process involved pulling magnetic beads through drops in an oil-enclosed environment. The purified nucleic acids were dispensed into microdroplets by a concentric-ring, oil-water-mixing, flow-focusing droplets generator driven under negative pressure conditions. Microdroplets were generated with good uniformity (CV = 5.8%), adjustable diameters (50-200 µm), and controllable flow rates (0-0.3 µL/s). Further verification was provided by quantitative detection of plasmids. We observed a linear correlation of R2 = 0.9998 in the concentration range from 10 to 105 copies/µL. Finally, this chip was applied to quantify the nucleic acid concentrations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The measured nucleic acid recovery rate of 75 ± 8.8% and detection limit of 10 copies/µL proved its on-chip purification and accurate detection abilities. This chip can potentially be a valuable tool in point-of-care testing.

An integrated microfluidic chip for nucleic acid extraction and continued cdPCR detection of pathogens.

This paper introduces an enclosed microfluidic chip that integrates sample preparation and the chamber-based digital polymerase chain reaction (cdPCR). The sample preparation of the chip includes nucleic acid extraction and purification based on magnetic beads, which adsorb nucleic acids by moving around the reaction chambers to complete the reactions including lysis, washing, and elution. The cdPCR area of the chip consists of tens of thousands of regularly arranged microchambers. After the sample preparation processes are completed, the purified nucleic acid can be directly introduced into the microchambers for amplification and detection on the chip. The nucleic acid extraction performance and digital quantification performance of the system were examined using synthetic SARS-CoV-2 plasmid templates at concentrations ranging from 101-105 copies per µL. Further on, a simulated clinical sample was used to test the system, and the integrated chip was able to accurately detect SARS-CoV-2 virus particle samples doped with interference (saliva) with a detection limit of 10 copies per µL. This integrated system could provide a promising tool for point-of-care testing of pathogenic infections.

Ecological Stoichiometric Characteristics in Organs of Ammopiptanthus mongolicus in Different Habitats.

The essence of plant ecological stoichiometry is to study the relationships between species and their environment, including nutrient absorption, utilization and cycling processes as well as the nutrient limitation of plants. Plants can regulate nutrient elements and adapt to environmental changes. To understand the adaptation mechanism, it is important to take plants as a whole and quantify the correlation between the chemometrics of different organs. Ammopiptanthus mongolicus is within the second-class group of rare−endangered plants in China and is the only evergreen broad-leaved shrub in desert areas. We analyzed the ecological stoichiometric characteristics of leaves, stems, roots, flowers and seeds of A. mongolicus in five habitats, namely fixed sandy land, semi-fixed sandy land, stony−sandy land, alluvial gravel slope and saline−alkali land. We found that (1) the nutrient contents of N, P and K were in the order of seed > flower > leaf > root > stem. The enrichment of the N, P and K in the reproductive organs promoted the transition from vegetative growth to reproductive growth. Additionally, (2) the contents of C, N, P and K and their stoichiometric ratios in different organs varied among different habitat types. The storage capacity of C, N and P was higher in sandy soil (fixed and semi-fixed sandy land), whereas the content of K was higher in gravelly soil (stony−sandy land and alluvial gravel slope), and the C:N, C:P and N:P were significantly higher in gravelly soil than those in sandy soil. A. mongolicus had higher nutrient use efficiency in stony−sandy land and alluvial gravel slope. Furthermore, (3) the C:N and N:P ratios in each organ were relatively stable among different habitats, whereas the K:P ratio varied greatly. The N:P ratios of leaves were all greater than 16 in different habitats, indicating that the growth was mainly limited by P. Moreover, (4) except for the P element, the content of each element and its stoichiometric ratio were affected by the interaction between organs and habitat. Habitat had a greater impact on C content, whereas organs had a greater influence on N, P and K content and C:N, C:P, C:K and N:P.

Additional health education and nutrition management cause more weight loss than concurrent training in overweight young females.

OBJECTIVE: This study aimed to compare the effect of concurrent training and the addition of health education and nutrition management on body composition and health-related outcomes. METHODS: Twenty-four healthy overweight females (20.42 ± 1.02 years, body mass index [BMI] 25.83 ± 3.63 kg∙m-2) were assigned to a concurrent training group (Exe, n = 12) or a concurrent training and health education group (Exe + Edu, n = 12). Both groups completed 8 weeks of concurrent training (6 days/week), whereas the Exe + Edu participants received additional health education and controlled daily energy intake within the basal metabolic rate. Body composition, serum glucose, lipids and related hormones were measured before and after intervention. RESULTS: After intervention, the Exe group lost 2.47 kg (±2.46) of body mass, 2.44 kg (±1.71) of total fat mass (FM), corresponding to a body fat percentage (BF%) of 2.25%. Losses of body mass, total FM and BF% in the Exe + Edu group were -5.19 ± 1.87 kg, -4.42 ± 1.83 kg and -4.33 ± 2.39%, respectively. The Exe + Edu participants had significantly greater reductions of body mass, total FM, and trunk and leg FM relative to the Exe participants (p < 0.05). Serum glucose, lipids, insulin and progesterone levels were improved in both groups without group difference. CONCLUSION: Concurrent training is an effective short-term training strategy for reducing FM and improving fasting glucose, blood lipids and related hormones. Furthermore, the combination of additional health education can achieve greater effects on weight loss and the reduction of total and regional FM, which may be a better obesity treatment method.

Fc effector of anti-Aß antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model.

Passive immunotherapy is one of the most promising interventions for Alzheimer's disease (AD). However, almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models. Here, we showed that Aß-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aß, antibody, and complement. Notably, anti-Aß antibodies without Fc fragment, or with blockage of CR3 or FcγRIIb, did not exert these adverse effects. Consistently, Aß-targeting antibodies, but not their Fab fragments, significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment, whereas the memory impairments in mice were gradually rescued thereafter. Since the recovery rate of synapses in humans is much lower than that in mice, our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies. Therefore, Aß-targeting antibodies lack of Fc fragment, or with reduced Fc effector function, may not induce microglial synaptic pruning, providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.

Measurement of local government green governance efficiency based on total waste emissions and PM2.5 concentration: Evidence from China.

The problem of environmental pollution is becoming more and more prominent. Making ecological governance take an effective and sustainable development path has become a complex problem for countries to think about. The proposal of green governance provides new ideas for governments to manage enterprises and local environmental governance. The DEA method is commonly used to measure the effectiveness of environmental governance, but the traditional DEA method ignores environmental factors and management factors, and the measurement error is significant. Therefore, this paper introduces the total waste discharge and PM2.5 average concentration and other unexpected outputs, using the three-stage DEA model and three-stage DEA Malmquist index model, creatively constructing the green governance measurement index system, which measures and evaluates the green governance efficiency of 30 provinces in China from 2004 to 2019 from static and dynamic perspectives. The research results show that the efficiency value obtained by the three-stage DEA model is higher than the first stage, which confirms that the external environmental factors have a specific impact on the GGE. At the same time, the comprehensive technical efficiency value presents a "U"-shaped trend with time. From the perspective of sub-regions, there is heterogeneity in the efficiency values between regions, showing a decreasing trend of "east, west, and middle." From the efficiency decomposition results, the main reason for the negative growth rate of GGE is the low efficiency of technological progress, which provides targeted suggestions for governance in various regions of China. This study will help provinces prepare to strengthen investment in technological innovation, maximize the benefits of input and output, and promote green and sustainable development.

Sarcopenia is an independent risk factor for depression in patients with advanced lung cancer.

BACKGROUND: Depression is the most prevalent psychological issue among cancer patients and can seriously affect patients' life and disease prognosis and even lead to suicide. Sarcopenia is a manifestation of cancer cachexia, a chronic progressive process. It is accompanied by a sustained decrease in skeletal muscle mass, muscle strength, and physical function and likewise has various negative effects on the patient. This study aimed to evaluate sarcopenia and other factors that may affect depression in patients with lung cancer and to further analyze and discuss. METHODS: A total of 104 eligible patients were enrolled in this cross-sectional study, using the Hamilton Depression Scale to assess depression, obtaining the psoas muscle index (PMI) by computed tomography (CT), and performing the diagnosis of sarcopenia. Clinical and personal characteristics were collected by electronic medical records. RESULTS: We evaluated a total of 104 hospitalized cancer patients in this analysis, with mean age = 57.8 ± 11.0 years, and 65.38% (68) were female. We found that up to 31.7% (33) of the participants had depression and 61.5% (64) of the participants had sarcopenia, and no statistical differences were found among depressed and non-depressed patients in relation to age, smoking, gender, performance status, and pathology. Patients with sarcopenia have more than four times the risk of suffering from depression than patients without sarcopenia (OR = 4.133, 95%CI = 1.390-12.287; p = 0.011). Similarly, the possibility of depression in patients with PD (progressive disease) as efficacy evaluation increased by 13.482 times (95%CI = 2.121-85.679, p = 0.006). CONCLUSION: In individuals with terminal lung cancer, depression and sarcopenia are prevalent. A strong association between the two is now thought to exist. Sarcopenia and efficacy evaluation are independent risk factors for depression. The correlation between sarcopenia and depression underscores the need for early intervention by our clinicians.

Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism.

We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 µM (IC50 = 103 ± 2 µM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the KI and KIS inhibition constants to be 117.07 µM and 423.63 µM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug.

Efficient Immunotherapy of Drug-Free Layered Double Hydroxide Nanoparticles via Neutralizing Excess Acid and Blocking Tumor Cell Autophagy.

Cancer immunotherapy efficacy is largely limited by the suppressive tumor immune microenvironment (TIME) where antitumor immune cells are inhibited and tumor antigens continue to mutate or be lost. To remodel the TIME, we here applied weakly alkaline layered double hydroxide nanoparticles (LDH NPs) to neutralize the excess acid and block autophagy of tumor cells for neoadjuvant cancer immunotherapy. Peritumoral injection of LDH NPs provided a long-term and efficient acid-neutralization in the TIME, blocked the lysosome-mediated autophagy pathway in tumor cells, and increased the levels of antitumor tumor-associated macrophages and T cells. These LDH NPs captured tumor antigens released in the tumor tissues and effectively inhibited the growth of both melanoma and colon tumors in vivo. These findings indicate that LDH NPs, as an immunomodulator and adjuvant, successfully "awaken" and promote the host innate and adaptive immune systems, showing promising potential for solid tumor immunotherapy.