[Research progress of trace amine-associated receptor 1 signaling pathways].

Trace amine-associated receptor 1 (TAAR1) is a classical type of G-protein-coupled receptor, which is widely distributed in the brain of mammals, especially in the limbic system and the region rich in monoaminergic neurons, and it is a highly conserved TAAR subtype in all species. TAAR1 can specifically respond to endogenous trace amines in the central nervous system and peripheral tissues, and plays an important role in the pathophysiological mechanisms involving the dysregulation of monoamine system and glutamate system leading to mental disorders. In addition, TAAR1 modulator can act on inwardly rectifying potassium channels and regulate synaptic transmission and neuronal activity. According to the latest research findings, TAAR1 exerts a series of functions by regulating signal pathways and substrate phosphorylation, which is related to emotion, cognition, fear and addiction. Therefore, we conducted a detailed review of relevant studies on the TAAR1 signaling pathways, aiming at revealing the great potential of TAAR1 as a new target for drug treatment of neuropsychiatric disorders.

Fluoxetine reverses early-life stress-induced depressive-like behaviors and region-specific alterations of monoamine transporters in female mice.

The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.

Biomass-Derived Carbon Materials for Electrochemical Energy Storage.

The environmental impact from the waste disposal has been widely concerned around the world. The conversion of wastes to useful resources is important for the sustainable society. As a typical family of wastes, biomass materials basically composed of collagen, protein and lignin are considered as useful resources for recycle and reuse. In recent years, the development of carbon material derived from biomasses, such as plants, crops, animals and their application in electrochemical energy storage have attracted extensive attention. Through the selection of the appropriate biomass, the optimization of the activation method and the control of the pyrolysis temperatures, carbon materials with desired features, such as high-specific surface area, variable porous framework, and controllable heteroatom-doping have been fabricated. Herein, this review summarized the preparation methods, morphologies, heteroatoms doping in the plant/animal-derived carbonaceous materials, and their application as electrode materials for secondary batteries and supercapacitors, and as electrode support for lithium-sulfur batteries. The challenges and prospects for the controllable synthesis and large-scale application of biomass-derived carbonaceous materials have also been outlooked.

Analysis of hindering and facilitating factors of help-seeking behavior in schizophrenia based on COM-B model: a descriptive qualitative study.

BACKGROUND: Timely and systematic professional treatment is crucial in schizophrenia prognosis, but the global rate of mental health service, now, use or help-seeking behavior is low. METHODS: In-depth semi-structured interviews were conducted with 13 participants with the diagnosis of schizophrenia between October to December 2021. The participants were purposively sampled from a psychiatric hospital's. Interviews were recorded and transcribed verbatim into NVivo 12.0. RESULTS: The findings were summarized under 3 themes and 12 subthemes: (1) capability (lack of knowledge due to insufficient mental health literacy or lack of insight, inability to access disease information due to a lack of mental health literacy, and symptoms-related barriers); (2) opportunity (lack of disease information sources, inability to balance work and study during prolonged hospitalization, accessibility and convenience of medical resources, and the acquisition and utilization of social support); and (3) motivation (awareness of the disease and professional treatment, negative experiences of disease episodes, past medical experience, confidence in tcuring the disease, and the fulfillment of daily life and self-worth). CONCLUSION: The medical help-seeking behavior of people with the diagnosis of schizophrenia is the result of the interaction of many barriers and facilitators, and challenges persist today. Interventions can be implemented with the BCW framework and our results to precisely eliminate delays in the diagnosis and treatment of mental problems.

The causal involvement of the BDNF-TrkB pathway in dentate gyrus in early-life stress-induced cognitive deficits in male mice.

Cognitive dysfunction is a significant, untreated clinical need in patients with psychiatric disorders, for which preclinical studies are needed to understand the underlying mechanisms and to identify potential therapeutic targets. Early-life stress (ELS) leads to long-lasting deficits of hippocampus-dependent learning and memory in adult mice, which may be associated with the hypofunction of the brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB). In this study, we carried out eight experiments using male mice to examine the causal involvement of the BDNF-TrkB pathway in dentate gyrus (DG) and the therapeutic effects of the TrkB agonist (7,8-DHF) in ELS-induced cognitive deficits. Adopting the limited nesting and bedding material paradigm, we first demonstrated that ELS impaired spatial memory, suppressed BDNF expression and neurogenesis in the DG in adult mice. Downregulating BDNF expression (conditional BDNF knockdown) or inhibition of the TrkB receptor (using its antagonist ANA-12) in the DG mimicked the cognitive deficits of ELS. Acute upregulation of BDNF (exogenous human recombinant BDNF microinjection) levels or activation of TrkB receptor (using its agonist, 7,8-DHF) in the DG restored ELS-induced spatial memory loss. Finally, acute and subchronic systemic administration of 7,8-DHF successfully restored spatial memory loss in stressed mice. Subchronic 7,8-DHF treatment also reversed ELS-induced neurogenesis reduction. Our findings highlight BDNF-TrkB system as the molecular target of ELS-induced spatial memory deficits and provide translational evidence for the intervention at this system in the treatment of cognitive deficits in stress-related psychiatric disorders, such as major depressive disorder.

The Growth and Conidiation of Purpureocillium lavendulum Are Co-Regulated by Nitrogen Sources and Histone H3K14 Acetylation.

Plant-parasitic nematodes cause severe economic losses to agriculture. As important biocontrol agents, nematophagous fungi evolved the ability to obtain nitrogen sources from nematodes. However, the impact of nitrogen sources on the growth and development of these fungi is largely unknown. In this study, we aimed to better understand how nitrogen sources could influence vegetative growth and conidiation through epigenetic regulation in the nematophagous fungus, Purpureocillium lavendulum. Through nutrition screening, we found a phenomenon of the fungus, limited colony extension with a large amount of conidia production when cultured on PDA media, can be altered by adding ammonia nitrate. Characterized by site-directed mutagenesis, the histone H3K14 acetylation was found to be involved in the alternation. Furthermore, the acetyltransferase PlGCN5 was responsible for H3K14 acetylation. Knockout of Plgcn5 severely diminished conidiation in P. lavendulum. Chip-seq showed that H3K14ac distributed in conidiation regulating genes, and genes in the MAPK pathway which may be the downstream targets in the regulation. These findings suggest that histone modification and nitrogen sources coordinated lifestyle regulation in P. lavendulum, providing new insight into the mechanism of growth regulation by nutritional signals for the carnivorous fungus.

Sexual needs of people with schizophrenia: a descriptive phenomenological study.

BACKGROUND: Sexual health is one of the main areas of health and basic human rights which has been paid less attention in schizophrenia. Most studies have focused on sexual dysfunction rather than the sexual needs of people with schizophrenia. This study explores the sexual needs of people with schizophrenia and identify factors hindering sexual activities. METHODS: We carried out a qualitative study using a descriptive phenomenological approach. Data were collected at a psychiatric hospital in China. In total, 20 patients with schizophrenia were recruited through purposive sampling. Face to face semi-structured in-depth interviews were conducted with them. Interview recordings were transcribed by the research team, and transcripts were analyzed by two independent coders with Colaizzi's descriptive analysis framework by using NVivo 11 software. The consolidated criteria for reporting qualitative research checklist was used for reporting. RESULTS: The data analysis revealed 10 subthemes categorized into 3 macro themes: (1) multiple barriers hinder sexual activity; (2) significance of sex; and (3) conditions for fulfilling sexual needs. CONCLUSION: A poor sexual quality of life may be found in patients with schizophrenia. Furthermore, people with schizophrenia did not lose interest in maintaining an active sex life. Mental health services should address this issue in three areas: sexual knowledge, sexual space, and sexual objects.

Analysis of the effects of apical backfilling depth on apical sealing of different root canal filling qualities and morphologies.

PURPOSE: The aim of this study was to evaluate the effects of apical backfilling depth on the apical sealing of different root canal filling qualities and morphologies. METHODS: 3D-printed root canals (A: round, B: oval, C: long oval, D: flat) were used and divided into subgroups by root canal filling quality (a: good, b: poor, c: nonfilling) and backfilling depth (3 mm, 5 mm). A glucose microleakage device was used to measure leakage. RESULTS: (1) 3-mm iRoot BP Plus was filled at the apex, and no obvious leakage occurred in the good root canal filling group, which was significantly smaller than that in the poor/nonfilling groups (P < 0.05). Under good root canal filling conditions in groups A, B, C, and D, no obvious leakage was observed. Under poor/nonfilling root canal filling conditions, there was significant leakage; A and B (P > 0.05) and C and D were compared (P < 0.05). (2) Apical backfilling with 5-mm iRoot BP Plus showed no significant leakage in the poor root canal filling groups with the four morphologies. CONCLUSION: 3-mm iRoot BP Plus was filled at the apex, root canal filling was poor, apical sealing was poor, and root canal morphology affected apical sealing. Apical backfilling with 5-mm iRoot BP Plus improved apical sealing under poor root canal filling conditions, and apical sealing was unaffected by root canal morphology.

Identification of the MALAT1/miR-106a-5p/ZNF148 feedback loop in regulating HaCaT cell proliferation, migration and apoptosis.

Aims: This study aims to investigate the function of positive feedback loops involving noncoding RNA in diabetic wound healing. Methods: We developed a mouse diabetic wound model to confirm that hyperglycemia can impair wound healing. We also used an in vitro keratinocyte model in high-glucose conditions to investigate the mechanism of delayed wound healing. Results: MALAT1 was decreased in diabetic mouse wound tissue and can promote keratinocyte biological functions. MALAT1 could bind to miR-106a-5p to modulate the expression of ZNF148, a target gene of miR-106a-5p. Surprisingly, ZNF148 bound to a region in the MALAT1 promoter to stimulate gene expression. Conclusion: ZNF148-activated MALAT1 increases ZNF148 expression by competitively binding miR-106a-3p, generating a positive feedback loop that enhances keratinocyte function.

Delayed wound repair is a leading cause of diabetic foot ulcers. However, the molecular mechanism underlying impaired wound healing in diabetes is unclear. In our study we found that a positive feedback loop consisting of MALAT1, miR-106a-5p and ZNF148 could promote chronic wound repair. In diabetic skin tissues, MALAT1 levels were lower, causing impairments in skin cell function. On a molecular level, MALAT1 can bind miR-106a-5p to increase ZNF148 levels. Surprisingly, ZNF148 can bind the promoter of MALAT1 to reverse the decline of MALAT1 levels in diabetic wounds. Our findings advance our understanding of chronic diabetic wounds and, more crucially, open new therapeutic possibilities for this disease.

The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse.

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.

One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α]D spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.8%-880.4% (25 µM) and 217.6%-1089.4% (50 µM), more potent than the positive control, oleoylethanolamide (250.2% at 50 µM). Moreover, compounds 4 and 6 exhibited agonistic activity on the G protein-coupled receptor (GPCR) TGR5 with stimulative ratios of 40.2% and 40.5% at 50 µM, and 54.2% and 49.1% at 100 µM, respectively. Docking study manifested that 6 well located in the catalytic pocket of TGR5 by hydrogen-bond and hydrophobic interactions. The GLP-1 promotion of 6 could be attenuated by IP3, Ca2+/CaMKII and MEK/ERK pathway inhibitors, suggesting that these pathways played important roles in GLP-1 secretion. Thus, stilbenes in peony seeds maybe regarded as potential GLP-1 secretagogues through TGR5-IP3-Ca2+/CaMKII-MEK/ERK pathways.

A decision support framework for postoperative radiotherapy in patients with pathological N2 non-small cell lung cancer.

INTRODUCTION: Postoperative radiotherapy (PORT) plays a highly controversial role in pathological N2 (pN2) non-small cell lung cancer (NSCLC) disease. Recent studies reveal that not all patients can benefit from PORT. Further research is needed to identify predictors of PORT. METHODS: A total of 1044 pathologic stage T1-3N2M0 NSCLC patients were analyzed. Risk factors of distant metastasis were identified by the log-rank tests and the multivariable Cox models. We integrated risk factors of distant metastasis and our previously published loco-regional recurrence (LRR) related prognostic index into a decision support framework (DSF) to predict the outcomes of PORT. An independent cohort was used to validate the DSF. RESULTS: We defined patients with more than two of three identified LRR-related features (heavy cigarette smoking history, clinical N2 status, and more than four positive lymph nodes) as a high LRR risk group. We found the high-intermediate-risk histological type (with micropapillary and/or solid components) was associated with a higher risk of distant metastasis (HR = 1.207, 95 % CI 1.062 to 1.371, P =  0.0038), but not LRR. We built the DSF by combining these two types of features. Patients were stratified into four groups by using the DSF. PORT significantly improved OS only in the subgroup without high-risk histological features (without micropapillary or solid components) and with a high risk for LRR (three-year OS: 66.7 % in the PORT group vs 50.2 % in the non-PORT group; P = 0.023). CONCLUSIONS: A particular pN2 subgroup with a high risk of LRR and without micropapillary or solid components could benefit from PORT.

Morphological changes of the root apex in anterior teeth with periapical periodontitis: an in-vivo study.

INTRODUCTION: The aim was to analyze the morphological changes of root apex in anterior teeth with periapical periodontitis. METHODS: 32 untreated anterior teeth with periapical periodontitis were enrolled, compared with the healthy contralateral teeth. Two-dimensional measurement of Cone-beam computed tomography was used to determine the location and measure diameter of the apical constriction according to Schell's methods. An open-source software (3D Slicer) was used to reconstruct the teeth. The apical constriction form was analysis according to Schell's topography. The distances of apical constriction to apical foramen and anatomical apex were measured respectively. RESULTS: The difference value between buccolingual and mesiodistal diameter was (0.06 ± 0.09) mm and (0.04 ± 0.04) mm in periapical periodontitis and controls (p < 0.05). The mean distance between apical constriction and anatomical apex was significantly shorter in periapical periodontitis than controls, so was the mean distance of apical constriction to apical foramen. The most common form of apical constriction was flaring (65.6%) in periapical periodontitis. CONCLUSIONS: The anterior teeth with periapical periodontitis had shorter distances of apical constriction to anatomical apex and apical foramen, bigger disparities between the diameters of buccolingual and mesiodistal, and higher proportion of flaring apical constriction.

Lymph Node Parameters Predict Adjuvant Chemoradiotherapy Efficacy and Disease-Free Survival in Pathologic N2 Non-Small Cell Lung Cancer.

Pathologic N2 non-small cell lung cancer (NSCLC) is prominently intrinsically heterogeneous. We aimed to identify homogeneous prognostic subgroups and evaluate the role of different adjuvant treatments. We retrospectively collected patients with resected pathologic T1-3N2M0 NSCLC from the Shanghai Chest Hospital as the primary cohort and randomly allocated them (3:1) to the training set and the validation set 1. We had patients from the Fudan University Shanghai Cancer Center as an external validation cohort (validation set 2) with the same inclusion and exclusion criteria. Variables significantly related to disease-free survival (DFS) were used to build an adaptive Elastic-Net Cox regression model. Nomogram was used to visualize the model. The discriminative and calibration abilities of the model were assessed by time-dependent area under the receiver operating characteristic curves (AUCs) and calibration curves. The primary cohort consisted of 1,312 patients. Tumor size, histology, grade, skip N2, involved N2 stations, lymph node ratio (LNR), and adjuvant treatment pattern were identified as significant variables associated with DFS and integrated into the adaptive Elastic-Net Cox regression model. A nomogram was developed to predict DFS. The model showed good discrimination (the median AUC in the validation set 1: 0.66, range 0.62 to 0.71; validation set 2: 0.66, range 0.61 to 0.73). We developed and validated a nomogram that contains multiple variables describing lymph node status (skip N2, involved N2 stations, and LNR) to predict the DFS of patients with resected pathologic N2 NSCLC. Through this model, we could identify a subtype of NSCLC with a more malignant clinical biological behavior and found that this subtype remained at high risk of disease recurrence after adjuvant chemoradiotherapy.

A New Technique for Placement of Blocking Screws and its Mechanical Effect on Stability of Tibia Fractures with Distal Fragments after Insertion of Small-Diameter Intramedullary Nails.

OBJECTIVE: To design a novel blocking screws (BSs) geometry and insertion method to treat distal tibia fracture with nailing and comparison of mechanical properties of novel and traditional screws. METHODS: Twenty-one synthetic left tibiae were sectioned to obtain 21 distal segments measuring 55 mm. Intramedullary (IM) 9-mm tibial nails were advanced to 6 mm from the ankle joint. Two transverse and one anterior-posterior (AP) locking screws were inserted. Both medial-lateral (ML) BSs were placed 10 mm from the topmost interlocking screw. A custom-made jig assisted in placing the novel and traditional BSs. The time spent in placing each BS was recorded. All the samples were repaired with an IM nail and without BSs, with two traditional BSs, and with two novel BSs. An initial loading from -150 to +150 N was applied to specimens in the ML direction at 185 mm from the nail end, followed by cyclic loading of the same for 10,000 cycles with failure-to-test loading of 350 N in the ML direction. The maximum displacement was measured at 80 mm from the nail end and recorded under initial loading. The damage of two kinds of BSs to the nail was recorded. RESULTS: Compared with average 5.21 min of the time of placing a traditional BS, the time spent in positioning a novel BS on the fracture model was 2.53 min. In the distal bone-implant constructs (BICs), the addition of traditional BSs decreased the maximum displacement of the BICs by 26.2%. The addition of the novel BSs decreased the displacement by 28.9%. All constructs survived 10,000 cycles without hardware deformation. The failure rate of the control group was significantly greater than that of the traditional group; however, the novel group was similar to the traditional group. The damage of the traditional BS to the nail was greater than that of the novel one. CONCLUSIONS: The novel and traditional BSs are comparably effective for increasing the primary mechanical stability of distal metaphyseal fractures after nailin. However, compared to the placement of a traditional BS, implanting a novel BS took more less time and caused less damage to the nail. Additionally, the most obvious advantage of the novel BS design and insertion technology was that the pressure and distance between it and the IM nail could be controlled by rotating the screw. These advantages of the novel BS will be beneficial for clinical application.

Prognostic index for estimating the survival benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: A real-world validation study.

OBJECTIVES: This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with resected pathologic N2 (pN2) non-small cell lung cancer (NSCLC) with different locoregional recurrence (LRR) risks. MATERIALS AND METHODS: The primary cohort and validation cohort were retrieved from two independent medical centres. Data for all consecutive patients with completely resected pathologic stage T1-3N2M0 NSCLC were analysed. Patients without PORT in the primary cohort were identified as a training set. Significant prognostic factors for LRR were identified by the Fine-Gray model to develop a prognostic index (PI) in the training set. RESULTS: The primary cohort consisted of 357 patients who met the eligibility criteria (training set, 287 patients without PORT). The external validation cohort consisted of 1044 patients who met the eligibility criteria (validation set, 711 patients without PORT). Heavy cigarette smoking history, clinical N2 status (cN2), and the number of positive lymph nodes >4 were identified as independent risk factors. The PI was computed as follows: PI＝0.8*smoking history＋0.5*cN2＋0.7*the number of involved lymph nodes (reference level was assigned the value 1 and risk level the value 2). In the low-risk group (PI score< = 3), PORT showed a trend towards decreased LRR rates but not significantly improved overall survival (OS). In the high-risk group (PI score>3), PORT significantly reduced the risk of LRR and improved OS. CONCLUSIONS: We constructed and validated a PI to predict individually the effect of PORT in patients with completely resected pN2 NSCLC. Patients with a higher PI score can benefit from PORT in terms of OS.

Role of trace amine­associated receptor 1 in the medial prefrontal cortex in chronic social stress-induced cognitive deficits in mice.

Emerging evidence supports an essential role of trace amine-associated receptor 1 (TAAR1) in neuropsychiatric disorders such as depression and schizophrenia. Stressful events are critical contributors to various neuropsychiatric disorders. This study examined the role of TAAR1 in mediating the negative outcomes of stressful events. In mice that experienced chronic social defeat stress but not acute stress, a significant reduction in the TAAR1 mRNA level was found in the medial prefrontal cortex (mPFC), a brain region that is known to be vulnerable to stress experience. Conditional TAAR1 knockout in the mPFC mimicked the cognitive deficits induced by chronic stress. In addition, chronic treatment with the selective TAAR1 partial agonist RO5263397 ameliorated chronic stress-induced changes in cognitive function, dendritic arborization, and the synapse number of pyramidal neurons in the mPFC but did not affect chronic stress-induced anxiety-like behaviors. Biochemically, chronic stress reduced the ratio of vesicular transporters of glutamate-1 (VGluT1) / vesicular GABA transporter (VGAT) in the mPFC，most prominently in the prelimbic cortex, and RO5263397 restored the excitatory-inhibitory (E/I) imbalance. Together, the results of this study reveal an essential role of TAAR1 in mediating chronic stress-induced cognitive impairments and suggest that TAAR1 agonists may be uniquely useful to treat MDD-related cognitive impairments.

Vortioxetine attenuates the effects of early-life stress on depression-like behaviors and monoamine transporters in female mice.

Major depressive disorder is a major psychiatric disorder and a leading cause of disability around the world. Females have about twice as high an incidence of depression as males. However, preclinical animal models of depression have seldom investigated the molecular alterations associated with higher depression risk in females. In this study, adopting the early-life stress (ELS) paradigm of limited bedding and nesting material, we found that ELS induced depression-like behaviors only in adult female mice, as evaluated by sucrose preference and tail suspension tests. We then examined the ELS effects on monoamine neurotransmission (transporters for monoamine reuptake and release) in depression-related brain regions in female mice. We found that ELS resulted in widespread changes of the expression levels of these transporters in four brain regions. Moreover, systemic 21-day treatment with vortioxetine, a novel multimodal antidepressant, successfully reversed depression-like behaviors and normalized some molecular changes, including that of the norepinephrine transporter in the medial prefrontal cortex, vesicular monoamine transporter 2 in nucleus accumbens core, and serotonin transporter in amygdala. Collectively, these results provide evidence for the validity of using the limited bedding and nesting material paradigm to investigate sex differences in depression and demonstrate that the region-specific alterations of monoamine neurotransmission may be associated with depression-like behaviors in female mice. This article is part of the special issue on 'Stress, Addiction and Plasticity'.

SH3PXD2A-AS1/miR-330-5p/UBA2 ceRNA network mediates the progression of colorectal cancer through regulating the activity of the Wnt/ß-catenin signaling pathway.

Long non-coding RNAs have important roles in the occurrence and progression of various cancers. However, the molecular mechanism of lncRNAs in colorectal cancer (CRC) is not well illustrated. Thus, we used bioinformatics methods to find potential lncRNAs associated with CRC progression, and chose SH3PXD2A-AS1 as a candidate for further analysis. The roles of SH3PXD2A-AS1 in CRC cells were determined by CCK-8, transwell invasion, wound healing and flow cytometry assays. Besides, we established the CRC tumor models in nude mice to study the effect of SH3PXD2A-AS1 on the tumor growth. Based on the ceRNA hypothesis, we used miRDB and miRTarBase websites to identify the SH3PXD2A-AS1-related ceRNA regulatory network, and measured the roles of this network in CRC cells. The results revealed that the expression profiles of SH3PXD2A-AS1 from GEO and TCGA databases showed an aberrant high level in CRC tissues compared with colorectal normal tissues. SH3PXD2A-AS1 over-expression was also found in CRC cells. SH3PXD2A-AS1 knockdown inhibited the CRC cellular proliferation, invasion and migration but induced apoptosis. Besides, SH3PXD2A-AS1 knockdown also suppressed the growth of CRC tumors. Furthermore, SH3PXD2A-AS1 could function as a ceRNA of miR-330-5p. Additionally, UBA2 was proved to be a target gene of miR-330-5p. Moreover, SH3PXD2A-AS1 knockdown downregulated UBA2 expression through sponging miR-330-5p to inactivate the Wnt/ß-catenin signaling pathway, thereby inhibiting the cell growth and promoting apoptosis. Therefore, the SH3PXD2A-AS1/miR-330-5p/UBA2 network could regulate the progression of CRC through the Wnt/ß-catenin pathway. These findings offer new sights for understanding the pathogenesis of CRC and provide potential biomarkers for CRC treatment.

Radiotherapy for non-small cell lung cancer in the immunotherapy era: the opportunity and challenge-a narrative review.

Immunotherapy has radically changed the clinical management of patients with cancer in recent years. Immune checkpoint inhibitors (ICIs) reversing the immunosuppressive effects of the tumor microenvironment are one type of immunotherapy, several of which are approved by the US Food and Drug Administration (FDA) as first-line treatments for patients with non-small cell lung cancer (NSCLC). However, response rates to ICIs are around 19-47% among patients with advanced NSCLC. As a result, the development of combined ICI and radiotherapy has begun with the aim of strengthening patients' antitumor immunity. Radiotherapy with substantial technological improvements not only achieves local tumor control through the induction of deoxyribonucleic acid (DNA) damage in irradiated regions, but also has the potential to mediate immunostimulatory effects that could result in tumor regression beyond irradiated regions. At present, numerous preclinical and clinical research are investigating the efficiency and safety of combining ICI with radiotherapy. The PACIFIC trial showed that combining chemoradiotherapy with ICI could improve clinical outcomes. In this review, we summarize the rationale for combining radiotherapy with immunotherapy. We also discuss the opportunities and challenges of combination therapy, including the timing of radiotherapy, optimal dose and fractionations, radiotherapy target and target volume, acquired resistance, patient selection, and radioimmunotherapy toxicity.