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Background The planting of mangroves is extensively used to control the invasive plant Spartina alterniflora in coastal wetlands. Different plant species release diverse sets of small organic compounds that affect rhizosphere conditions and support high levels of microbial activity. The root-associated microbial community is crucial for plant health and soil nutrient cycling, and for maintaining the stability of the wetland ecosystem. Methods High-throughput sequencing was used to assess the structure and function of the soil bacterial communities in mudflat soil and in the rhizosphere soils of S. alterniflora, mangroves, and native plants in the Oujiang estuarine wetland, China. A distance-based redundancy analysis (based on Bray–Curtis metrics) was used to identify key soil factors driving bacterial community structure. Results S. alterniflora invasion and subsequent mangrove afforestation led to the formation of distinct bacterial communities. The main soil factors driving the structure of bacterial communities were electrical conductivity (EC), available potassium (AK), available phosphorus (AP), and organic matter (OM). S. alterniflora obviously increased EC, OM, available nitrogen (AN), and NO3−-N contents, and consequently attracted copiotrophic Bacteroidates to conduct invasion in the coastal areas. Mangroves, especially Kandelia obovata, were suitable pioneer species for restoration and recruited beneficial Desulfobacterota and Bacilli to the rhizosphere. These conditions ultimately increased the contents of AP, available sulfur (AS), and AN in soil. The native plant species Carex scabrifolia and Suaeda glauca affected coastal saline soil primarily by decreasing the EC, rather than by increasing nutrient contents. The predicted functions of bacterial communities in rhizosphere soils were related to active catabolism, whereas those of the bacterial community in mudflat soil were related to synthesis and resistance to environmental factors. Conclusions Ecological restoration using K. obovata has effectively improved a degraded coastal wetland mainly through increasing phosphorus availability and promoting the succession of the microbial community.

Abstract Lithium (Li) is a well-established mood disorder treatment and may be neuroprotective. Bi-directional regulation (i.e. affecting manic symptoms and depressive symptoms) by Li has not been demonstrated. This study explored: (1) bidirectional regulation by Li in murine models of depression, mania, and bipolar disorder (BP); and (2) potential Li synergism with antidepressant/anti-mania agents. The chronic unpredictable mild stress (CUMS) and ketamine-induced mania (KM) models were used. These methods were used in series to produce a BP model. In vivo two-photon imaging was used to visualize Ca2+ activity in the dorsolateral prefrontal cortex. Depressiveness, mania, and cognitive function were assessed with the forced swim task (FST), open field activity (OFA) task, and novel object recognition task, respectively. In CUMS mice, Ca2+ activity was increased strongly by Li and weakly by lamotrigine (LTG) or valproate (VPA), and LTG co-administration reduced Li and VPA monotherapy effects; depressive immobility in the FST was attenuated by Li or LTG, and attenuated more strongly by LTG-VPA or LTG-Li; novel object exploration was increased strongly by Li and weakly by LTG-Li, and reduced by LTG, VPA, or LTG-VPA. In KM mice, Li or VPA attenuated OFA mania symptoms and normalized Ca2+ activity partially; Li improved cognitive function while VPA exacerbated the KM alteration. These patterns were replicated in the respective BP model phases. Lithium had bi-directional, albeit weak, mood regulation effects and a cognitive supporting effect. Li co-administration with antidepressant/-manic agents enhanced mood-regulatory efficacy while attenuating their cognitive-impairing effects.

Summary: Cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (RB) are both important cell-cycle regulators that function in different scenarios. Here, we report that FERM domain-containing 8 (FRMD8) inhibits CDK4 activation and stabilizes RB, thereby causing cell-cycle arrest and inhibiting colorectal cancer (CRC) cell growth. FRMD8 interacts separately with CDK7 and CDK4, and it disrupts the interaction of CDK7 with CDK4, subsequently inhibiting CDK4 activation. FRMD8 competes with MDM2 to bind RB and attenuates MDM2-mediated RB degradation. Frmd8 deficiency in mice accelerates azoxymethane/dextran-sodium-sulfate-induced colorectal adenoma formation. The FRMD8 promoter is hypermethylated, and low expression of FRMD8 predicts poor prognosis in CRC patients. Further, we identify an LKCHE-containing FRMD8 peptide that blocks MDM2 binding to RB and stabilizes RB. Combined application of the CDK4 inhibitor and FRMD8 peptide leads to marked suppression of CRC cell growth. Therefore, using an LKCHE-containing peptide to interfere with the MDM2-RB interaction may have therapeutic value in CDK4/6 inhibitor-resistant patients.

Abstract Schizophrenia is a severe mental illness, as the efficacies of current antipsychotic medications are far from satisfactory. An improved understanding of the signaling molecules involved in schizophrenia may provide novel therapeutic targets. Acid sphingomyelinase (ASM) catalyzes cellular membrane sphingomyelin into ceramide, which is further metabolized into sphingosine-1-phophate (S1P). ASM, ceramide, and S1P at the cell surface exert critical roles in the regulation of biophysical processes that include proliferation, apoptosis, and inflammation, and are thereby considered important signaling molecules. Although research on the ASM/ceramide system is still in its infancy, structural and metabolic abnormalities have been demonstrated in schizophrenia. ASM/ceramide system dysfunction is linked to the two important models of schizophrenia, the dopamine (DA) hypothesis through affecting presynaptic DA signaling, and the vulnerability-stress-inflammation model that includes the contribution of stress on the basis of genetic predisposition. In this review, we highlight the current knowledge of ASM/ceramide system dysfunction in schizophrenia gained from human and animal studies, and formulate future directions from the biological landscape for the development of new treatments. Collectively, these discoveries suggest that aberrations in the ASM/ceramide system, especially in ASM activity and levels of ceramide and S1P, may alter cerebral microdomain structure and neuronal metabolism, leading to neurotransmitter (e.g., DA) dysfunction and neuroinflammation. As such, the ASM/ceramide system may offer therapeutic targets for novel medical interventions. Normalization of the aberrant ASM/ceramide system or ceramide reduction by using approved functional inhibitors of ASM, such as fluvoxamine and rosuvastatin, may improve clinical outcomes of patients with schizophrenia. These transformative findings of the ASM/ceramide system in schizophrenia, although intriguing and exciting, may pose scientific questions and challenges that will require further studies for their resolution.

Abstract Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.

The occurrence of heavy menstrual bleeding (HMB) induced by pharmacological agents has been reported in young adult women. This study aimed to investigate a possible association between the occurrence rates of HMB and different treatment methods such as antidepressant agents alone and in combination with other pharmacological agents. The examined cohort included young women (age 18–35 years, n = 1,949) with bipolar disorder (BP) or major depressive disorder (MDD). Menstruation history for 24 months was recorded and evaluated according to pictorial blood loss assessment charts of HMB. Multivariate analyses were conducted to determine odds ratios (ORs) and 95% confidence intervals. The examined antidepressant agents had varying ORs for patients with BP vs. those with MDD. For example, the ORs of venlafaxine-induced HMB were 5.27 and 4.58 for patients with BP and MDD, respectively; duloxetine-induced HMB, 4.72 and 3.98; mirtazapine-induced HMB, 3.26 and 2.39; fluvoxamine-induced HMB, 3.11 and 2.08; fluoxetine-induced HMB, 2.45 and 1.13; citalopram-induced HMB, 2.03 and 1.25; escitalopram-induced HMB, 1.85 and 1.99; agomelatine-induced HMB, 1.45 and 2.97; paroxetine-induced HMB, 1.19 and 1.75; sertraline-induced HMB, 0.88 and 1.13; reboxetine-induced HMB, 0.45 and 0.45; and bupropion-induced HMB, 0.33 and 0.37, in each case. However, when antidepressant agents were combined with valproate, the OR of HMB greatly increased, with distinct profiles observed for patients with BP vs. those with MDD. For example, the ORs of HMB induced by venlafaxine combined with valproate were 8.48 and 6.70 for patients with BP and MDD, respectively; for duloxetine, 5.40 and 4.40; mirtazapine, 5.67 and 3.73; fluvoxamine, 5.27 and 3.37; fluoxetine, 3.69 and 4.30; citalopram, 5.88 and 3.46; escitalopram, 6.00 and 7.55; agomelatine, 4.26 and 5.65; paroxetine, 5.24 and 3.25; sertraline, 4.97 and 5.11; reboxetine, 3.54 and 2.19; and bupropion, 4.85 and 3.46, in each case. In conclusion, some antidepressant agents exhibited potential risks of inducing HMB. Therefore, a combined prescription of antidepressant agents and valproate should be carefully considered for young women with HMB.

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

Lithium monotherapy has been proposed to have antidepressant and antimanic effects in patients with bipolar disorder (BP). However, so far, it is lack of evidence to support this proposition. The main aim of this study was to test the hypothesis that lithium bidirectionally regulates depression- and mania-related brain functional abnormalities in patients with BP. We also assessed the effects of lithium, alone and in combination with other pharmacological treatments, on patients' cognitive performance. We enrolled 149 drug-naïve patients with BP; 99 patients experiencing first depressive episodes were allocated randomly to four treatment groups [lithium (DP/Li), lithium with lamotrigine (LTG; DP/Li+LTG), LTG (DP/LTG), and valproate (VPA) with LTG (DP/VPA+LTG)], and 50 experiencing first hypo-manic episodes were allocated to two treatment groups (MA/Li and MA/VPA). For comparative analysis, 60 age-matched healthy individuals were also recruited. Whole-brain global and regional resting-state cerebral blood flow (rs-CBF) and cognitive alterations were examined before and after 12-week treatment. We have the following findings: DP/Li+LTG, and to a lesser extent DP/Li, alleviated the depression-related reduction in rs-CBF. MA/VPA and MA/Li reversed the mania-related elevation of rs-CBF completely and partially, respectively. Lithium alone improved cognitive performance during depressive and manic episodes; other tested treatments have no such effect or worsened cognitive ability. Our results showed that lithium bidirectionally regulates depression- and mania-associated brain functional abnormalities in patients with BP. Lithium monotherapy has a better antimanic effect than VPA, is superior to other tested treatments in improving cognition during the course of BP, and has satisfactory antidepressant effects in patients with BP.

BackgroundThere is no standard effective treatment for schizophrenia-associated cognitive impairment. Efforts to use non-invasive brain stimulation for this purpose have been focused mostly on the frontal cortex, with little attention being given to the occipital lobe.Materials and methodsWe compared the effects of nine intervention strategies on cognitive performance in psychometric measures and brain connectivity measured obtained from functional magnetic resonance imaging analyses. The strategies consisted of transcranial direct current stimulation (t-DCS) or repetitive transcranial magnetic stimulation (r-TMS) of the frontal lobe or of the occipital alone or with adjunct lithium, or lithium monotherapy. We measured global functional connectivity density (gFCD) voxel-wise.ResultsAlthough all nine patient groups showed significant improvements in global disability scores (GDSs) following the intervention period (vs. before), the greatest improvement in GDS was observed for the group that received occipital lobe-targeted t-DCS with adjunct lithium therapy. tDCS of the occipital lobe improved gFCD throughout the brain, including in the frontal lobes, whereas stimulation of the frontal lobes had less far-reaching benefits on gFCD in the brain. Adverse secondary effects (ASEs) such as heading, dizziness, and nausea, were commonly experienced by patients treated with t-DCS and r-TMS, with or without lithium, whereas ASEs were rare with lithium alone.ConclusionThe most effective treatment strategy for impacting cognitive impairment and brain communication was t-DCS stimulation of the occipital lobe with adjunct lithium therapy, though patients often experienced headache with dizziness and nausea after treatment sessions.

Cognitive impairment is highly prevalent in patients with major psychiatric disorders (MPDs), including schizophrenia (SCZ), bipolar disorder, major depressive disorder, in whom it can be highly disruptive to community functioning and worsen prognosis. Previously, genetic factors and cognitive impairments in MPD patients have been examined mostly in isolated circuits rather than in the whole brain. In the present study, genetic, neuroimaging, and psychometric approaches were combined to investigate the relationship among genetic factors, alterations throughout the brain, and cognitive impairments in a large cohort of patients diagnosed with SCZ, with a reference healthy control (HC) group. Single nucleotide polymorphisms (SNPs) in SCZ-risk genes were found to be strongly related to cognitive impairments as well as to gray matter volume (GMV) and functional connectivity (FC) alterations in the SCZ group. Annotating 136 high-ranking SNPs revealed 65 affected genes (including PPP1R16B, GBBR2, PDE4B, CANCNA1C, SLC12AB, SATB2, MAG12, and SATB2). Only one, a PDE4B SNP (rs1006737), correlated with GMV (r = 0:19 p = 0.015) and FC (r = 0.21, p = 0.0074) in SCZ patients. GMV and FC alterations correlated with one another broadly across brain regions. Moreover, the present data demonstrate three-way SNP-FC-GMV associations in patients with SCZ, thus providing clues regarding potential genetic bases of cognition impairments in SCZ. SNP-FC-GMV relationships correlated with visual learning and reasoning dimensions of cognition. These data provide evidence that SCZ-related cognitive impairments may reflect genetically underlain whole-brain structural and functional alterations.

BackgroundCognitive performance improves clinical outcomes of patients with major psychiatric disorder (MPD), but is impaired by hyperglycemia. Psychotropic agents often induce metabolism syndrome (MetS). The identification of modifiable metabolic risk factors of cognitive impairment may enable targeted improvements of patient care.ObjectiveTo investigate the relationship between MetS and cognitive impairment in young women with MPD, and to explore risk factors.MethodsWe retrospectively studied women of 18–34 years of age receiving psychotropic medications for first-onset schizophrenia (SCH), bipolar disorder (BP), or major depressive disorder (MDD). Data were obtained at four time points: presentation but before psychotropic medication; 4–8 and 8–12 weeks of psychotropic therapy; and enrollment. MATRICS Consensus Cognitive Battery, (MCCB)—based Global Deficit Scores were used to assess cognitive impairment. Multiple logistic analysis was used to calculate risk factors. Multivariate models were used to investigate factors associated with cognitive impairment.ResultsWe evaluated 2,864 participants. Cognitive impairment was observed in 61.94% of study participants, and was most prevalent among patients with BP (69.38%). HbA1c within the 8–12 week-treatment interval was the most significant risk factor and highest in BP. Factors in SCH included pre-treatment waist circumference and elevated triglycerides during the 8–12 weeks treatment interval. Cumulative dosages of antipsychotics, antidepressants, and valproate were associated with cognitive impairment in all MPD subgroups, although lithium demonstrated a protect effect (all P < 0.001).ConclusionsCognitive impairment was associated with elevated HbA1c and cumulative medication dosages. Pre-treatment waist circumference and triglyceride level at 8–12 weeks were risk factors in SCH. Monitoring these indices may inform treatment revisions to improve clinical outcomes.

There has been limited studies examining treatment-induced heavy menstrual bleeding (HMB) in women with severe mental illnesses. The aim of this study was to examine HMB prevalence and HMB-associated factors in young women (18–34 years old) diagnosed with bipolar disorder (BP), major depressive disorder (MDD), or schizophrenia (SCZ) who have full insight and normal intelligence. Eighteen-month menstruation histories were recorded with pictorial blood loss assessment chart assessments of HMB. Multivariate analyses were conducted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Drug effects on cognition were assessed with the MATRICS Consensus Cognitive Battery (MCCB). HMB prevalence were: BP, 25.85%; MDD, 18.78%; and SCH, 13.7%. High glycosylated hemoglobin (HbA1c) level was a strong risk factor for HMB [BP OR, 19.39 (16.60–23.01); MDD OR, 2.69 (4.59–13.78); and SCZ OR, 9.59 (6.14–12.43)]. Additional risk factors included fasting blood sugar, 2-h postprandial blood glucose, and use of the medication valproate [BP: OR, 16.00 (95%CI 12.74–20.22); MDD: OR, 13.88 (95%CI 11.24–17.03); and SCZ OR, 11.35 (95%CI 8.84–19.20)]. Antipsychotic, antidepressant, and electroconvulsive therapy use were minor risk factors. Pharmacotherapy-induced visual learning impairment was associated with HMB [BP: OR, 9.01 (95%CI 3.15–13.44); MDD: OR, 5.99 (95%CI 3.11–9.00); and SCZ: OR, 7.09 (95%CI 2.99–9.20)]. Lithium emerged as a protective factor against HMB [BP: OR, 0.22 (95%CI 0.14–0.40); MDD: OR, 0.30 (95%CI 0.20–0.62); and SCZ: OR, 0.65 (95%CI 0.33–0.90)]. In SCZ patients, hyperlipidemia and high total cholesterol were HMB-associated factors (ORs, 1.87–2.22). Psychiatrist awareness of HMB risk is concerningly low (12/257, 2.28%). In conclusion, prescription of VPA should be cautioned for women with mental illness, especially BP, and lithium may be protective against HMB.

This study aimed to investigate the safety and efficacy of high-dose vitamin B6 (vB6) as an adjunct treatment for antipsychotic-induced hyperprolactinemia (AIHP) in male patients with treatment-resistant schizophrenia (TRS). In this randomized double-blinded controlled study, patients were randomized (1:1) into a control group given aripiprazole (ARI; 10 mg/day; n = 100) or an intervention group given vB6 (300 mg/12 h for 16 weeks; n = 100). Prolactin levels, psychotic symptoms [Positive and Negative Syndrome Scale (PANSS)], cognitive function [MATRICS Consensus Cognitive Battery (MCCB)], liver function, kidney function, growth hormone level, micronutrient levels, blood lipids, and adverse secondary effects (ASEs)[Treatment Emergent Symptom Scale (TESS) and Barnes-Akathisia scale] were monitored. After a 16-week treatment period, the vB6 group showed a 68.1% reduction in serum prolactin levels (from 95.52 ± 6.30 μg/L to 30.43 ± 18.65 μg/L) while the ARI group showed only a 37.4% reduction (from 89.07 ± 3.59 μg/L to 55.78 ± 7.39 μg/L). During weeks 1–4, both treatments reduced prolactin similarly. Subsequently, the ARI effect plateaued, while the vB6 effect remained robust. The vB6 group showed better alleviation of psychotic symptoms and cognitive impairment. No serious ASEs were observed; ASEs were more frequent in the ARI group. AIHP reduction efficacy of vB6 was associated with baseline prolactin and triglyceride levels, total vB6 dosage, and education level. In conclusion, compared with the ARI group, TRS patients given vB6 showed better attenuation of AIHP, lower ASE scores, and greater improvements in clinical symptoms and cognitive impairments. These results support further consideration of vB6 as a putative treatment for AIHP.Trial Registration: ChiCTR1800014755

This study aimed to investigate the efficacy of cold plasma activated water (PAW) and its complex solution (PKC) in conjunction with kasugamycin copper oxychloride wettable powder (KC) against kiwifruit bacterial canker (KBC) caused by Pseudomonas syringae pv. actinidiae (PSA). Through morphological identification and 16S rDNA sequence analysis, Pantoea agglomerans was identified as the pathogen responsible for KBC in the 'Bairui' orchard. Results indicated that PKC exhibited the highest effectiveness in controlling KBC, particularly on mildly (II) infested plants, with a remarkable reduction of 63.64 % in PKC II disease index and a control efficiency of 38.64 %. Additionally, the application of PKC significantly increased fruit yield, improved fruit weight, and enhanced fruit morphology, resulting in a more uniform and refined fruit shape. Analysis of fruit skin conformational parameters revealed that KBC-affected fruit exhibited reduced hardness and brittleness, increased toughness, and thinner skin. These findings are pivotal for developing effective strategies to further prevent and manage KBC outbreaks. In future studies, further investigations could focus on elucidating the mechanism of action of PAW in complex solution with copper-based pesticides and the potential mechanism of inactivation of PSA.

Abstract The functionalization of the β‐carbon of enals with electrophiles is a signature umpolung reactivity of N‐heterocyclic carbene (NHC) derived homoenolates. However, only a limited number of electrophiles are shown to be compatible, with most of them being π‐electrophiles. In this study, the successful enantioselective β‐alkylation of homoenolates is reported using Csp3 electrophiles through an SN2 strategy. The protocol shows a broad scope regarding alkyl electrophiles, delivering good yields, and excellent enantioselectivities (up to 99% ee). It enables the installation of drug‐like structural motifs in either enals or alkylating agents, demonstrating its potential as a valuable tool for late‐stage modification. Furthermore, a concise synthetic route is presented to chiral pyrroloindoline‐type skeletons. Preliminary mechanistic studies support a direct SN2 mechanism.

Integrins in the cell surface interact with functional motifs found in the extracellular matrix (ECM) that queue the cell for biological actions such as migration, adhesion, or growth. Multiple fibrous proteins such as collagen or fibronectin compose the ECM. The field of biomechanical engineering often deals with the design of biomaterials compatible with the ECM that will trigger cellular response (e.g., in tissue regeneration). However, there are a relative few number of known integrin binding motifs compared to all the possible peptide epitope sequences available. Computational tools could help identify novel motifs, but have been limited by the challenges in modeling the binding to integrin domains. We revisit a series of traditional and novel computational tools to assess their performance in identifying novel binding motifs for the I-domain of the α2β1 integrin.

BackgroundAlthough previous studies have explored the moderating role of emotional regulation strategies in the relationship between empathy and depression, no studies have studied the moderating role of attentional control in the relationship between empathy and depression. To address this research gap, the present study investigated the moderating roles of rumination and attentional control in the relationship between empathy and depression.Methods423 participants filled out questionnaires anonymously, including Interpersonal Reactivity Index, Attention Control Scale, Self-rating Depression Scale, and Rumination Response Scale. PROCESS macro for SPSS was used for moderating effect analysis.ResultsRumination and attentional shift moderated the relationship between emotional empathy and depression. Specifically, the lower rumination or the higher attentional shift, the stronger the negative association between emotional empathy and depression. Attentional shift moderated the relationship between cognitive empathy and depression, and cognitive empathy was significantly associated with depression only among participants whose attentional shift is high.ConclusionThe study showed that rumination and attentional shift play important roles in the relationship between empathy and depression. The findings implicated that the positive role of good emotional regulation strategies and executive function for individuals in the relationship between empathy and depression.

Abstract Background Thin endometrium negatively impacts the reproductive function. Current treatments for thin endometrium do not always improve endometrial receptivity. Preliminary evidence suggests that electroacupuncture could have potential therapy for thin endometrium in infertile women. Thus, this randomized controlled trial was designed to test whether electroacupuncture can improve endometrial receptivity in infertile women with thin endometrium. Methods This study is a randomized, single-blinded, controlled, clinical trial. A total of 142 eligible patients will be recruited and randomly assigned to the electroacupuncture (EA) group or the sham electroacupuncture (SEA) group in a 1:1 ratio. Participants will receive 36 sessions over three menstrual cycles (12 weeks in total), with the same acupoint prescription. The primary outcome of this trial is endometrial thickness in the midluteal phase. The secondary outcomes include endometrial pattern, resistance index (RI) and pulsatility index (PI) of bilateral uterine artery and endometrium blood flow, serum estradiol (E2) and progesterone (P), and pregnancy rate. The pregnancy rate will be evaluated during a 6-month follow-up after completion of the trial. All other outcomes will be evaluated before treatment, during the treatment of 1st, 2nd, and 3rd menstrual cycle, and 6 months after treatment. Discussion If the outcome confirms the effectiveness of electroacupuncture for thin endometrium in infertile women, this treatment will be proposed for application in clinical practice. Trial registration Chinese Clinical Trials Registry ChiCTR2 000029983. Registered on 18 February 2020

Introduction The increased social and economic burden caused by the novel COVID-19 outbreak is gradually becoming a worrisome issue for the health sector. The novel coronavirus invades the target cell by binding to ACE2, which is widely expressed in the ovaries, uterus, vagina and placenta. Significantly, the SARS-CoV-2 is said to interrupt female fertility through regulating ACE2. Thus, it is essential to investigate if the novel COVID-19 hampers female fertility, given that there is no systematic and comprehensive evidence on the association of COVID-19 with female fertility.Methods and analysis We will systematically search cohort studies, cross-sectional studies, case–control studies and self-controlled case series designs in the following databases: Web of Science, PubMed, EMBASE, Cochrane Library, Ovid, EBSCO, WHO COVID-19 Database, Chinese Biomedical Databases, China National Knowledge Internet, VIP and WanFang Database. Medical Subject Headings and free-text terms for “COVID-19” AND “female” AND “fertility” will be performed. Eligibility criteria are as follows: population (female patients aged 13–49 years); exposure (infection with SARS-CoV-2); comparison (population without SARS-CoV-2 infections or latent SARS-CoV-2 infections); and outcome (female fertility, such as ovarian reserve function, uterine receptivity, oviducts status and menstruation status). Article screening and data extraction will be undertaken independently by two reviewers, and discrepancies will be resolved through discussion. We will use the I2 statistics to assess the heterogeneity and perform a meta-analysis when sufficiently homogeneous studies are provided. Otherwise, a narrative synthesis will be performed. We will explore the potential sources of heterogeneity using subgroup analyses and meta-regression.Ethics and dissemination Formal ethical approval is not required, and findings will be published in a peer-reviewed journal.PROSPERO registration number CRD42020189856.

Objective: HOXB9 is an important transcription factor associated with unfavorable outcomes in LUAD. However, natural degradation mechanism remains unclear. Methods: IHC, co-IP, gene knockout mice, Xenograft tumor formation assay, RT-qPCR, Transcriptome Sequencing, In vivo ubiquitination assays, Dual Luciferase Reporter Assay, Chromatin Immunoprecipitation, PET Imaging of Glucose Uptake in Mice and LC-MS/MS analysis. Results: Here, we showed that HOXB9 is a substrate of AMPKα and is phosphorylated at T133. Glucose deprivation and metformin treatment facilitated AMPKα-mediated HOXB9 phosphorylation, downregulating HOXB9 in AMPKα knockout mice and LUAD cells. Mechanistically, phosphorylated HOXB9 promoted E3 ligase Praja2-mediated HOXB9 degradation. Blocking HOXB9 phosphorylation by depleting AMPKα1/2 or using the HOXB9 T133A mutant promoted tumor cell growth in cell culture and mouse xenografts through upregulation of HOXB9 and KRAS, a newly identified target of HOXB9. Clinically, AMPK activation levels in LUAD samples were positively correlated with pHOXB9, and higher pHOXB9 indicated better survival of patients with LUAD. Conclusion: These findings reveal the degradation mechanism of HOXB9 and presence of an AMPK--HOXB9--KRAS axis linking glucose level-regulated AMPK activation to HOXB9 stability and KRAS gene expression, ultimately controlling LUAD progression. [ABSTRACT FROM AUTHOR]