On the Carboniferous Sequence Stratigraphy in the Tazhong Area, Xinjiang——A Model of the Sequence Stratigraphy Framework of Intracratonic Depressional Basins

The Carboniferous prototype sedimentary basin in the Tazhong (Central Tarimbasin) area is recognized as a compressive intracratonic depressional one. Three type Ⅰ sequenceboundaries and three type Ⅱ sequence boundaries can be identified in the CarboniferousSystem, which can accordingly be divided into five sedimentary sequences. These sequencespossess stratigraphic characters of the standard sequence and correspond to the depositionalstratigraphic unit of a third-order eustatic cycle. They can be regionally or globally correlatedwith each other. The framework of sequence stratigraphy of the intracratonict basin in thestudy area distinctly differs from that of the passive continental-margin basin in the lack ofdepositional systems of early-middle lowstand, poor development of the deeply incised valleyand condensed section of the maximum sea-flood, good development of type Ⅱ sequenceboundaries and coastal plain depositional systems coexisting with shelf-type fan deltas underwet climatic conditions, Which consequently led to the formation of a paralic lithofacies frame-work.

Understanding the spectrum of non-motor symptoms in multiple sclerosis:insights from animal models

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.

Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies.In this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome.Moreover,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating depression.Additionally,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression.Currently,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment.The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression.Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

Lactate:a prospective target for therapeutic intervention in psychiatric disease

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

Late Triassic Intracontinental Deformation of South Tianshan,Central Asia:Evidence from Syn-tectonic Sedimentation and Detrital Zircon Provenances of the Kuqa Depression

The Tianshan range,a Paleozoic orogenic belt in Central Asia,has undergone multiple phases of tectonic activities characterized by the N-S compression after the early Mesozoic,including the far-field effects of the Cenozoic Indian-Asian collision.However,there are limited reports on the tectonic deformation and initiation of Triassic intracontinental deformation in the Tianshan range.Understanding this structural context is crucial for interpreting the early intracontinental deformation history of the Eurasian continent during the early Mesozoic.Growth strata and syn-tectonic sediments provide a rich source of information on tectonic activities and have been extensively used in the studies of orogenic belts.Based on detail fieldwork conducted in this study,the middle-late Triassic Kelamayi Formation of the northern Kuqa Depression in the southern Tianshan fold-thrust belt has been identified as the typical syn-tectonic growth strata.The youngest detrital zircon component in two lithic sandstone samples from the bottom and top of the Kelamayi growth strata yielded U-Pb ages of 223.4±3.1 and 215.5±2.9 Ma,respectively,indicating that the maximum depositional age of the bottom and top of the Kelamayi growth strata is 226-220 and 218-212 Ma.The geochronological distribution of detrital samples from the Early-Middle Triassic and Late Triassic revealed abrupt changes,suggesting a new source supply resulting from tectonic activation in the Tianshan range.The coupling relationship between the syn-tectonic sedimentation of the Kelamayi Formation and the South Tianshan fold-thrust system provides robust evidence that the Triassic intracontinental deformation of the South Tianshan range began at approximately 226-220 Ma(during the Late Triassic)and ended at approximately 218-212 Ma.These findings provide crucial constraints for understanding the intraplate deformation in the Tianshan range during the Triassic.

Differences and identification on multi-time hydrocarbon generation of carboniferous-permian coaly source rocks in the Huanghua Depression,Bohai Bay Basin

Coal is a solid combustible mineral,and coal-bearing strata have important hydrocarbon generation potential and contribute to more than 12%of the global hydrocarbon resources.However,the deposition and hydrocarbon evolution process of ancient coal-bearing strata is characterized by multiple geological times,leading to obvious distinctions in their hydrocarbon generation potential,geological processes,and production,which affect the evaluation and exploration of hydrocarbon resources derived from coaly source rocks worldwide.This study aimed to identify the differences on oil-generated parent macerals and the production of oil generated from different coaly source rocks and through different oil generation processes.Integrating with the analysis of previous tectonic burial history and hydrocarbon generation history,high-temperature and high-pressure thermal simulation experiments,organic geochemistry,and organic petrology were performed on the Carboniferous-Permian(C-P)coaly source rocks in the Huanghua Depression,Bohai Bay Basin.The oil-generated parent macerals of coal's secondary oil generation process(SOGP)were mainly hydrogen-rich collotelinite,collodetrinite,sporinite,and cutinite,while the oil-generated parent macerals of tertiary oil generation process(TOGP)were the remaining small amount of hydrogen-rich collotelinite,sporinite,and cutinite,as well as dispersed soluble organic matter and unexhausted residual hydrocarbons.Compared with coal,the oil-generated parent macerals of coaly shale SOGP were mostly sporinite and cutinite.And part of hydrogen-poor vitrinite,lacking hydrocarbon-rich macerals,and macerals of the TOGP,in addition to some remaining cutinite and a small amount of crude oil and bitumen from SOGP contributed to the oil yield.The results indicated that the changes in oil yield had a good junction between SOGP and TOGP,both coal and coaly shale had higher SOGP aborted oil yield than TOGP starting yield,and coaly shale TOGP peak oil yield was lower than SOGP peak oil yield.There were significant differences in saturated hydrocarbon and aromatic parameters in coal and coaly shale.Coal SOGP was characterized by a lower Ts/Tm and C31-homohopane22S/(22S+22R)and a higher Pr/n C17compared to coal TOGP,while the aromatic parameter methyl dibenzothiophene ratio(MDR)exhibited coaly shale TOGP was higher than coaly shale SOGP than coaly TOGP than coaly SOGP,and coal trimethylnaphthalene ratio(TNR)was lower than coaly shale TNR.Thus,we established oil generation processes and discriminative plates.In this way,we distinguished the differences between oil generation parent maceral,oil generation time,and oil production of coaly source rocks,and therefore,we provided important support for the evaluation,prediction,and exploration of oil resources from global ancient coaly source rocks.

The occurrence characteristics of oil in shales matrix from organic geochemical screening data and pore structure properties:An experimental study Author links open overlay panel

The occurrence characteristics of shale oil are of great significance to the movability of shale oil.In this study,the occurrence characteristics of oil in the shale matrix at Funing Formation shale in Subei Basin were quantitatively evaluated by organic geochemistry and microscopic pore structure characterization experiments.The Multiple Isothermal Stages Pyrolysis(MIS)experiment results show that the content of total oil,adsorbed oil,and free oil in the shales are 3.15-11.25 mg/g,1.41-4.95 mg/g,and 1.74-6.51 mg/g,respectively.among which the silicon-rich shale has the best oil-bearing.The relative content of free oil shows an increasing trend in pores with pore diameters greater than 3 nm.When the relative content of free oil reaches 100%,the pore size of silicon-rich shale is about 200 nm,while that of calcium-rich shale,clay-rich shale,and siliceous mixed shale is about 10 nm.The occurrence law of adsorbed oil is opposite to that of free oil,which indicates that shale oil will occur in the pores and fractures in a free state in a more extensive pore size range(>200 nm).This study also enables us to further understand the occurrence characteristics of shale oil under the interaction of occurrence state and occurrence space.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

Quantitative effect of kerogen type on the hydrocarbon generation potential of Paleogene lacustrine source rocks,Liaohe Western Depression,China

Kerogen types exert a decisive effect on the onset and capacity of hydrocarbon generation of source rocks.Lacustrine source rocks in the Liaohe Western Depression are characterized by thick deposition,high total organic carbon(TOC)content,various kerogen types,and a wide range of thermal maturity.Consequently,their hydrocarbon generation potential and resource estimation can be misinterpreted.In this study,geochemical tests,numerical analysis,hydrocarbon generation kinetics,and basin modeling were integrated to investigate the differential effects of kerogen types on the hydrocarbon generation potential of lacustrine source rocks.Optimized hydrocarbon generation and expulsion(HGE)models of different kerogen types were established quantitatively upon abundant Rock-Eval/TOC/vitrinite reflectance(R_(o))datasets.Three sets of good-excellent source rocks deposited in the fourth(Es4),third(Es3),and first(Es1)members of Paleogene Shahejie Formation,are predominantly types I-II_(1),II_(1)-II_(2),and II-III,respectively.The activation energy of types I-II_(2)kerogen is concentrated(180-230 kcal/mol),whereas that of type III kerogen is widely distributed(150-280 kcal/mol).The original hydrocarbon generation potentials of types I,II_(1),II_(2),and III kerogens are 790,510,270,and 85 mg/g TOC,respectively.The Ro values of the hydrocarbon generation threshold for type I-III source rocks gradually increase from 0.42%to 0.74%,and Ro values of the hydrocarbon expulsion threshold increase from 0.49%to 0.87%.Types I and II_(1)source rocks are characterized by earlier hydrocarbon generation,more rapid hydrocarbon expulsion,and narrower hydrocarbon generation windows than types II_(2)and III source rocks.The kerogen types also affect the HGE history and resource potential.Three types(conventional,tight,and shale oil/gas)and three levels(realistic,expected,and prospective)of hydrocarbon resources of different members in the Liaohe Western Depression are evaluated.Findings suggest that the Es3 member has considerable conventional and unconventional hydrocarbon resources.This study can quantitatively characterize the hydrocarbon generation potential of source rocks with different kerogen types,and facilitate a quick and accurate assessment of hydrocarbon resources,providing strategies for future oil and gas exploration.

Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.

Depression Intensity Classification from Tweets Using Fast Text Based Weighted Soft Voting Ensemble

Predicting depression intensity from microblogs and social media posts has numerous benefits and applications,including predicting early psychological disorders and stress in individuals or the general public.A major challenge in predicting depression using social media posts is that the existing studies do not focus on predicting the intensity of depression in social media texts but rather only perform the binary classification of depression and moreover noisy data makes it difficult to predict the true depression in the social media text.This study intends to begin by collecting relevant Tweets and generating a corpus of 210000 public tweets using Twitter public application programming interfaces(APIs).A strategy is devised to filter out only depression-related tweets by creating a list of relevant hashtags to reduce noise in the corpus.Furthermore,an algorithm is developed to annotate the data into three depression classes:‘Mild,’‘Moderate,’and‘Severe,’based on International Classification of Diseases-10(ICD-10)depression diagnostic criteria.Different baseline classifiers are applied to the annotated dataset to get a preliminary idea of classification performance on the corpus.Further FastText-based model is applied and fine-tuned with different preprocessing techniques and hyperparameter tuning to produce the tuned model,which significantly increases the depression classification performance to an 84%F1 score and 90%accuracy compared to baselines.Finally,a FastText-based weighted soft voting ensemble(WSVE)is proposed to boost the model’s performance by combining several other classifiers and assigning weights to individual models according to their individual performances.The proposed WSVE outperformed all baselines as well as FastText alone,with an F1 of 89%,5%higher than FastText alone,and an accuracy of 93%,3%higher than FastText alone.The proposed model better captures the contextual features of the relatively small sample class and aids in the detection of early depression intensity prediction from tweets with impactful performances.

Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD patients.However,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain unclear.Methods:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice.Changes in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were examined.In addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice.Results:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive impairments.These mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal cortex.Furthermore,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis.Abnormal expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also observed.Conclusion:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice.The mechanism may involve the induction of central and peripheral lipid metabolism disorders.Therefore,modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression.This study also provided a better animal model for studying AD comorbid with depression.

Advances in depressants for flotation separation of Cu–Fe sulfide minerals at low alkalinity:A critical review

The flotation separation of Cu–Fe sulfide minerals at low alkalinity can be achieved using selective depressants.In the flotation system of Cu–Fe sulfide minerals,depressants usually preferentially interact with the pyrite surface to render the mineral surface hydrophilic and hinder the adsorption of the collector.This review summarizes the advances in depressants for the flotation separation of Cu–Fe sulfide minerals at low alkalinity.These advances include use of inorganic depressants (oxidants and sulfur–oxygen compounds),natural polysaccharides (starch,dextrin,konjac glucomannan,and galactomannan),modified polymers (carboxymethyl cellulose,polyacrylamide,lignosulfonate,and tricarboxylate sodium starch),organic acids (polyglutamic acid,sodium humate,tannic acid,pyrogallic acid,salicylic acid,and lactic acid),sodium dimethyl dithiocarbamate,and diethylenetriamine.The potential application of specific inorganic and organic depressants in the flotation separation of Cu–Fe sulfide minerals at low alkalinity is reviewed.The advances in the use of organic depressants with respect to the flotation separation of Cu–Fe sulfide minerals are comprehensively detailed.Additionally,the depression performances and mechanisms of different types of organic depressants on mineral surfaces are summarized.Finally,several perspectives on depressants vis-à-vis flotation separation of Cu–Fe sulfide minerals at low alkalinity are proposed.

Potential role of hippocampal neurogenesis in spinal cord injury induced post-trauma depression

It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.

Double role of depression in gastric cancer:As a causative factor and as consequence

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression,elucidating the curative mechanism of Danzhi Xiaoyao powder

Objective:To investigate the molecular mechanism and identify potential drugs for subthreshold depression(SD),and elucidate the detalied mechanism of Danzhi Xiaoyao powder(DZXY)in SD.Methods:Using RNA-sequencing,we identified differentially expressed genes(DEGs)in leukocytes of SD compared to healthy controls,deciphered their functions and pathways,and identified the hub genes of SD.We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELis platform.The Connectivity Map database was retrieved to screen candidate drugs for SD.Based on network pharmacology,we elucidated the"multi-component,multi-target,and multi-pathway"mechanism of DZXY in the treatment of SD.Results:We identified 1080 DEGs(padj<0.05 and|log2(fold change)l≥1&protein coding)in the leukocytes of patients with SD.These DEGs,including hub genes,were primarily involved in immune and inflammatory response-related processes.Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells.Connectivity Map analysis identified 28 potential drugs for SD treatment,particularly SB-202190 and TWS-119.Constructing the"Direct Compounds-Direct Targets-Pathways"network for DZXY and SD revealed the curative mechanisms of DZXY in SD,primarily including inflammatory response,lipid metabolism,immune response,and other processes.Conclusion:These results provide new insights into the characteristics and functional changes of leukocytes in SD,partially illustrate the pathogenesis of SD,and suggest potential drugs for SD.The curative mechanisms of DZXY in SD are also partially elucidated.