Brain-heart interaction disruption in major depressive disorder: disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts.

Brain neurons support arousal and cognitive activity in the form of spectral transient bursts and cooperate with the peripheral nervous system to adapt to the surrounding environment. However, the temporal dynamics of brain-heart interactions have not been confirmed, and the mechanism of brain-heart interactions in major depressive disorder (MDD) remains unclear. This study aimed to provide direct evidence for brain-heart synchronization in temporal dynamics and clarify the mechanism of brain-heart interaction disruption in MDD. Eight-minute resting-state (closed eyes) electroencephalograph and electrocardiogram signals were acquired simultaneously. The Jaccard index (JI) was used to measure the temporal synchronization between cortical theta transient bursts and cardiac cycle activity (diastole and systole) in 90 MDD patients and 44 healthy controls (HCs) at rest. The deviation JI was used to reflect the equilibrium of brain activity between diastole and systole. The results showed that the diastole JI was higher than the systole JI in both the HC and MDD groups; compared to HCs, the deviation JI attenuated at F4, F6, FC2, and FC4 in the MDD patients. The eccentric deviation JI was negatively correlated with the despair factor scores of the HAMD, and after 4 weeks of antidepressant treatment, the eccentric deviation JI was positively correlated with the despair factor scores of the HAMD. It was concluded that brain-heart synchronization existed in the theta band in healthy individuals and that disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts at right frontoparietal sites led to brain-heart interaction disruption in MDD.

Sex differences in anhedonia in bipolar depression: a resting-state fMRI study.

Previous studies about anhedonia symptoms in bipolar depression (BD) ignored the unique role of gender on brain function. This study aims to explore the regional brain neuroimaging features of BD with anhedonia and the sex differences in these patients. The resting-fMRI by applying fractional amplitude of low-frequency fluctuation (fALFF) method was estimated in 263 patients with BD (174 high anhedonia [HA], 89 low anhedonia [LA]) and 213 healthy controls. The effects of two different factors in patients with BD were analyzed using a 3 (group: HA, LA, HC) × 2 (sex: male, female) ANOVA. The fALFF values were higher in the HA group than in the LA group in the right medial cingulate gyrus and supplementary motor area. For the sex-by-group interaction, the fALFF values of the right hippocampus, left medial occipital gyrus, right insula, and bilateral medial cingulate gyrus were significantly higher in HA males than in LA males but not females. These results suggested that the pattern of high activation could be a marker of anhedonia symptoms in BD males, and the sex differences should be considered in future studies of BD with anhedonia symptoms.

Attenuated post-movement beta rebound reflects psychomotor alterations in major depressive disorder during a simple visuomotor task: a MEG study.

BACKGROUND: Psychomotor alterations are a common symptom in patients with major depressive disorder (MDD). The primary motor cortex (M1) plays a vital role in the mechanism of psychomotor alterations. Post-movement beta rebound (PMBR) in the sensorimotor cortex is abnormal in patients with motor abnormalities. However, the changes in M1 beta rebound in patients with MDD remain unclear. This study aimed to primarily explore the relationship between psychomotor alterations and PMBR in MDD. METHODS: One hundred thirty-two subjects were enrolled in the study, comprising 65 healthy controls (HCs) and 67 MDD patients. All participants performed a simple right-hand visuomotor task during MEG scanning. PMBR was measured in the left M1 at the source reconstruction level with the time-frequency analysis method. Retardation factor scores and neurocognitive test performance, including the Digit Symbol Substitution Test (DSST), the Making Test Part A (TMT-A), and the Verbal Fluency Test (VFT), were used to measure psychomotor functions. Pearson correlation analyses were used to assess relationships between PMBR and psychomotor alterations in MDD. RESULTS: The MDD group showed worse neurocognitive performance than the HC group in all three neurocognitive tests. The PMBR was diminished in patients with MDD compared to HCs. In a group of MDD patients, the reduced PMBR was negatively correlated with retardation factor scores. Further, there was a positive correlation between the PMBR and DSST scores. PMBR is negatively associated with the TMT-A scores. CONCLUSION: Our findings suggested that the attenuated PMBR in M1 could illustrate the psychomotor disturbance in MDD, possibly contributing to clinical psychomotor symptoms and deficits of cognitive functions.

Association of Circulating Trimethylamine-N Oxide With Malnutrition and the Risk of Coronary Artery Disease in Patients With Maintenance Hemodialysis.

OBJECTIVES: Malnutrition is a serious complication frequently observed in dialysis patients. Therefore, nutrition status evaluation and the early identification of malnutrition are clinically important. Trimethylamine N-oxide (TMAO) is reportedly associated with deteriorating metabolic profiles and cardiovascular diseases. The aim of our study was to investigate correlations between circulating TMAO levels and malnutrition and the risk of major adverse cardiovascular events in patients on maintenance hemodialysis. METHODS: This retrospective observational study involved 228 subjects. Fasting plasma TMAO levels were detected using liquid chromatography-tandem mass spectrometry. RESULTS: TMAO levels were significantly elevated in patients with malnutrition (8728.78 ± 704.12 ng/mL) when compared with those without (6532.1 ± 570.41 ng/mL, P < .01). TMAO levels were positively correlated with Subjective Global Assessment scores (ρ = 0.56, P = .02) and were independent risk factors for malnutrition after adjustment for multiple traditional risk factors (odds ratio = 2.07, 95% confidence interval: 1.41-3.62, P < .01). Furthermore, TMAO levels were good predictors of major adverse cardiovascular events in a 2-year follow-up period (area under the curve = 0.68, P < .01) and accuracy was increased to 74% when TMAO levels were combined with Subjective Global Assessment scores (area under the curve = 0.74, P = .02). CONCLUSIONS: Elevated TMAO levels were independently associated with a risk of malnutrition and cardiovascular disease, and could be a useful predictive biomarker for risk stratification and cardiovascular disease management for patients on dialysis.

Double Addition of Alkynyllithium Reagents to Amides/Lactams: A Direct and Flexible Synthesis of 3-Amino-1,4-diynes Bearing an Aza-Quaternary Carbon Center.

An efficient and mild protocol for the direct and flexible synthesis of 3-amino-1,4-diynes bearing an aza-quaternary carbon from tertiary amides and lactams has been established. The one-pot method consists of in situ activation of amides with trifluoromethanesulfonic anhydride, followed by double addition of alkynyllithium reagents at a concentration of 0.5 mol·L-1 in dichloromethane. This constitutes an extension of the method of direct reductive bisalkylation of amides that allows both employing alkynyllithium reagents as the first-addition nucleophiles and incorporating an alkynyl group as the first-introduced group.

Metal-Free Intermolecular Coupling of Arenes with Secondary Amides: Chemoselective Synthesis of Aromatic Ketimines and Ketones, and N-Deacylation of Secondary Amides.

The direct transformation of common secondary amides into aromatic ketimines and aromatic ketones with C-C bond formation is described. The reaction can also be used for N-deacylation of secondary amides to release amines. This method consists of in situ amide activation with triflic anhydride and intermolecular capture of the resulting highly electrophilic nitrilium intermediate with an arene. The reaction is applicable to various kinds of secondary amides (electrophiles), but only electron-rich and moderately electron-rich arenes can be used as nucleophiles. Thanks to the use of bench stable arenes instead of reactive and basic organometallics as nucleophiles, the reaction proceeded with high chemoselectivity at the secondary amido group in the presence of a series of sensitive functional groups such as aldehyde, ketone, ester, cyano, nitro, and tertiary amido groups. The reaction can be viewed as a Friedel-Crafts-type reaction using secondary amides as acylating agents or as an intermolecular version of the Bischler-Napieralski reaction.

Research Advances in the Intervention of Inflammation and Cancer by Active Ingredients of Traditional Chinese Medicine.

A large body of evidence has shown that inflammation and cancer are strongly related. Thus anti-inflammatory agents have been investigated for cancer prevention and treatment in preclinical and clinical studies, including the nonsteroidal anti-inflammatory drugs (NSAIDs) and traditional Chinese medicine (TCM). In TCM, there exist a wide range of biologically active substances, such as saponins, flavonoids, alkaloids, polysaccharides, polyphenols, phenylpropanoids, and quinones. Many of these active ingredients have been reported to inhibit inflammation, activate inflammatory immune response, and/or inhibit cancer cell proliferation and tumor growth. Given the potential role of inflammation in cancer initiation and progression, the inflammatory tumor microenvironment, the cross-talks between inflammatory and cancer cells, and multitargeting activities of some TCM compounds, we summarize the current knowledge on the anti-inflammatory and anti-cancer properties of ingredients of TCM together with their underlying mechanisms in an integrated way. We hope to provide a reliable basis and useful information for the development of new treatment strategies of inflammation and cancer comprehensively using TCM and their active ingredients.

A general method for the one-pot reductive functionalization of secondary amides.

A one-pot reaction for the transformation of common secondary amides into amines with C-C bond formation is described. This method consists of in situ amide activation with Tf2O-partial reduction-addition of C-nucleophiles. The method is general in scope, which allows employing both hard nucleophiles (RMgX, RLi) and soft nucleophiles, as well as enolates. With the use of soft nucleophiles, the reaction proceeded with high chemoselectivity at a secondary amide in the presence of ester, cyano, nitro, and tertiary amide groups.

Novel pillar[n]arenes magnetic nanoparticles: Preparation and application in quantitative analysis of trace perfluorinated compounds from aqueous samples.

BACKGROUND: Perfluorinated compounds (PFCs) are a class of widely manufactured and used emerging persistent pollutants. The recent discovered new class of macrocycles pillararenes have garnered significant attention for the applications in environmental pollutant adsorption, with abundant π electron cavities, a symmetrical rigid structure, and host-guest recognition capabilities. RESULTS: In this work, we designed and synthesized novel cationic pillar [n]arenes magnetic nanoparticles (CWPA5@MNPs), and investigated its adsorption performance and mechanism as a type of new adsorbent for the enrichment of PFCs. The results indicate that CWPA5@MNPs exhibits selectively strong affinity for perfluorooctane sulfonate (PFOS) and long-chain (C9-C14) perfluorocarboxylic acids (PFCAs), with the adsorption efficiency exceeding 80 % within 12 min. The maximum adsorption capacity of CWPA5@MNPs for PFOS was measured to be 29.02 mg/g. CWPA5@MNPs can be rapidly isolated from the solution using external magnets, offering a quick and easy separation. Consequently, this study established a CWPA5@MNPs-assisted magnetic solid-phase extraction (MSPE) coupled with high-performance liquid chromatography-tandem mass spectrometry (CWPA5@MNPs-MSPE-HPLC-MS/MS) method for the rapid detection of trace levels of PFCs in environmental water samples. The analysis of 7 PFCs yielded recovery rates ranging from 86.1 % to 107.5 %, with intraday and interday relative standard deviations (RSD) of 3.6-6.4 % and 1.3-7.0 %, respectively. SIGNIFICANCE AND NOVELTY: The study reveals the synthesis and application of novel cationic pillar [n]arenes magnetic nanoparticles (CWPA5@MNPs) as highly efficient adsorbents for selective perfluorinated compounds (PFCs) in water samples. It demonstrates the potential of the newly developed CWPA5@MNPs-MSPE-HPLC-MS/MS method for the quantitative analysis of PFCs in environment, with high sensitivity, accuracy and stability.

Based on white matter microstructure to early identify bipolar disorder from patients with depressive episode.

OBJECTIVE: Because of similar clinical manifestations, bipolar disorder (BD) patients are often misdiagnosed as major depressive disorder (MDD). This study aimed to compare the difference between depressed patients later converting to BD and unipolar depression (UD) according to diffusion tensor imaging (DTI). METHOD: Patients with MDD (562 participants) in depressive episode states and healthy controls (HCs) (145 participants) were recruited over 10 years. Demographic and magnetic resonance imaging (MRI) data were collected at the time of recruitment. All patients with MDD were followed up for 5 years and classified into the transfer to BD (tBD) group (83 participants) and UD group (160 participants) according to the follow-up results. DTI and functional magnetic resonance imaging at baseline were compared. RESULTS: Common abnormalities were found in both tBD and UD groups, including left superior cerebellar peduncle (SCP.L), right anterior limb of the internal capsule (ALIC.R), right superior fronto-occipital fasciculus (SFOF.R), and right inferior fronto-occipital fasciculus (IFOF.R). The tBD showed more extensive abnormalities than the UD in the body of corpus callosum, fornix, left superior corona radiata, left posterior corona radiata, left superior longitudinal fasciculus, and left superior fronto-occipital fasciculus. CONCLUSION: The study demonstrated the common and distinct abnormalities of tBD and UD when compared to HC. The tBD group showed more extensive disruptions of white matter integrity, which could be a potential biomarker for the early identification of BD.

Significance of N6-methyladenosine RNA methylation regulators in diagnosis and subtype classification of primary Sjögren's syndrome.

The importance of N6-methyladenine (m6A) in mRNA metabolism, physiology, pathology and other life processes is well recognized. However, the exact role of m6A regulators in primary Sjögren's syndrome (PSS) remains unclear. In this study, we used bioinformatics and machine learning random forest approach to screen eight key m6A regulators from the Gene Expression Omnibus GSE7451, GSE40611 and GSE84844 datasets. An accurate nomogram model for predicting PSS risk was established based on these regulators. And using consensus clustering, patients diagnosed with PSS were classified into two different m6A patterns. We found that patients in group B had higher m6A scores compared to those in group A: furthermore, both groups were closely related to immunity and possibly to other diseases. These results emphasise the important role of m6A regulators in the pathogenesis of PSS. Our study of m6A patterns may inform future immunotherapy strategies for PSS.

Abnormal stability of spontaneous neuronal activity as a predictor of diagnosis conversion from major depressive disorder to bipolar disorder.

OBJECTIVE: Bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD) in the early stage, which may lead to inappropriate treatment. This study aimed to characterize the alterations of spontaneous neuronal activity in patients with depressive episodes whose diagnosis transferred from MDD to BD. METHODS: 532 patients with MDD and 132 healthy controls (HCs) were recruited over 10 years. During the follow-up period, 75 participants with MDD transferred to BD (tBD), and 157 participants remained with the diagnosis of unipolar depression (UD). After excluding participants with poor image quality and excessive head movement, 68 participants with the diagnosis of tBD, 150 participants with the diagnosis of UD, and 130 HCs were finally included in the analysis. The dynamic amplitude of low-frequency fluctuations (dALFF) of spontaneous neuronal activity was evaluated in tBD, UD and HC using functional magnetic resonance imaging at study inclusion. Receiver operating characteristic (ROC) analysis was performed to evaluate sensitivity and specificity of the conversion prediction from MDD to BD based on dALFF. RESULTS: Compared to HC, tBD exhibited elevated dALFF at left premotor cortex (PMC_L), right lateral temporal cortex (LTC_R) and right early auditory cortex (EAC_R), and UD showed reduced dALFF at PMC_L, left paracentral lobule (PCL_L), bilateral medial prefrontal cortex (mPFC), right orbital frontal cortex (OFC_R), right dorsolateral prefrontal cortex (DLPFC_R), right posterior cingulate cortex (PCC_R) and elevated dALFF at LTC_R. Furthermore, tBD exhibited elevated dALFF at PMC_L, PCL_L, bilateral mPFC, bilateral OFC, DLPFC_R, PCC_R and LTC_R than UD. In addition, ROC analysis based on dALFF in differential areas obtained an area under the curve (AUC) of 72.7%. CONCLUSIONS: The study demonstrated the temporal dynamic abnormalities of tBD and UD in the critical regions of the somatomotor network (SMN), default mode network (DMN), and central executive network (CEN). The differential abnormal patterns of temporal dynamics between the two diseases have the potential to predict the diagnosis transition from MDD to BD.

Comparison of oXiris and Conventional Continuous Renal Replacement Therapy in Managing Severe Abdominal Infections: Impact on Septic Shock Mortality.

OBJECTIVE: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. METHODS: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index (OI), lactate (Lac), platelet count (PLT), neutrophil ratio (N%), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), norepinephrine (NE) dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) were recorded prior to treatment initiation, at 24 hours, and 72 hours post-treatment for both the oXiris and conventional CRRT groups. Additionally, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, as well as mortality rates at 14 and 28 days for both groups were recorded. RESULTS: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 hours post-treatment compared to pre-treatment levels. Also, at 72 hours post-treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, OI, N%, and IL-6 at 24 hours post-treatment when compared to baseline values. Additionally, reductions were observed in APACHE II and SOFA scores. At 72 hours post-treatment, all parameters demonstrated enhancement except for PLT. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 hours post-treatment revealed variances in HR, MAP, Lac, NE dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 hours post-treatment indicated more significant improvements following oXiris treatment for both groups, except for PCT. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared to the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. CONCLUSION: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option.

T2T reference genome assembly and genome-wide association study reveal the genetic basis of Chinese bayberry fruit quality.

Chinese bayberry (Myrica rubra or Morella rubra; 2n = 16) produces fruit with a distinctive flavor, high nutritional, and economic value. However, previous versions of the bayberry genome lack sequence continuity. Moreover, to date, no large-scale germplasm resource association analysis has examined the allelic and genetic variations determining fruit quality traits. Therefore, in this study, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the cultivar 'Zaojia' using PacBio HiFi long reads. The resulting 292.60 Mb T2T genome, revealed 8 centromeric regions, 15 telomeres, and 28 345 genes. This represents a substantial improvement in the genome continuity and integrity of Chinese bayberry. Subsequently, we re-sequenced 173 accessions, identifying 6 649 674 single nucleotide polymorphisms (SNPs). Further, the phenotypic analyses of 29 fruit quality-related traits enabled a genome-wide association study (GWAS), which identified 1937 SNPs and 1039 genes significantly associated with 28 traits. An SNP cluster pertinent to fruit color was identified on Chr6: 3407532 to 5 153 151 bp region, harboring two MYB genes (MrChr6G07650 and MrChr6G07660), exhibiting differential expression in extreme phenotype transcriptomes, linked to anthocyanin synthesis. An adjacent, closely linked gene, MrChr6G07670 (MLP-like protein), harbored an exonic missense variant and was shown to increase anthocyanin production in tobacco leaves tenfold. This SNP cluster, potentially a quantitative trait locus (QTL), collectively regulates bayberry fruit color. In conclusion, our study presented a complete reference genome, uncovered a suite of allelic variations related to fruit-quality traits, and identified functional genes that could be harnessed to enhance fruit quality and breeding efficiency of bayberries.

Abnormal fractional amplitude of low-frequency fluctuations and regional homogeneity in major depressive disorder with non-suicidal self-injury.

OBJECTIVE: We conducted this resting-state functional magnetic resonance imaging (rsfMRI) study to characterize changes in regional homogeneity (ReHo) or fractional amplitude of low-frequency fluctuations (fALFF) in young adult patients with major depressive disorder (MDD), with or without non-suicidal self-injury (NSSI). METHODS: We recruited 54 MDD patients with NSSI (MDD/NSSI), 68 MDD patients without NSSI, which is referred to as simple MDD (sMDD), and 66 matched healthy controls (HCs). A combination of fALFF and ReHo analyses was conducted. The effects of NSSI on the brain and their relationship to clinical variables were examined in this study. RESULTS: MDD/NSSI patients have decreased fALFF in the right superior frontal gyrus (SFG) and the right inferior parietal lobe (IPL), decreased ReHo in the right SFG and the right middle temporal gyrus (MTG) and the left middle occipital gyrus (MOG). fALFF and ReHo values of the right SFG are positively correlated. The ReHo values of the right SFG and the number of recent self-injuries are positively correlated; the fALFF values of the right SFG are negatively correlated with NSSI severity. CONCLUSIONS: There is a difference in brain activity between MDD/NSSI and sMDD, which may serve as an important physiological marker to determine the risk of self-injury and suicide. SIGNIFICANCE: Abnormal brain activity in patients with NSSI may provide new perspectives and significant implications on the severity of MDD patients and the prevention of self-injury and suicide.

A direct and general method for the reductive alkylation of tertiary lactams/amides: application to the step economical synthesis of alkaloid (-)-morusimic acid D.

Full details of the direct and general method for the reductive alkylation of tertiary lactams and amides to give tertiary sec-alkylamines are presented. This one-pot method consists of in situ activation of a lactam or an amide with Tf2O/DTBMP, addition of a Grignard reagent, and reduction of the resulting iminium intermediates. Alkyl, benzyl, and aryl Grignard reagents and several reductants or reducing conditions (LiAlH4, NaBH4, Hantzsch ester, Bu3SnH, Pd(OH)2/C, H2) could be used effectively. Reductive alkylations of substituted lactams demonstrated good to excellent 1,3-asymmetric induction to provide the corresponding di- or trisubstituted pyrrolidine/piperidine in 6:1 (LiAlH4), 11:1 (Et3SiH), and 20:1 (catalytic hydrogenation) cis/trans diastereoselectivity, respectively. The versatility of this methodology was demonstrated by its application in the concise stereoselective synthesis of piperidine alkaloid (-)-morusimic acid.

The relationship between disrupted anhedonia-related circuitry and suicidal ideation in major depressive disorder: A network-based analysis.

BACKGROUND: Several epidemiological studies and psychological models have suggested that major depressive disorder (MDD) with anhedonia is associated with suicidal ideation (SI). However, little is known about whether the functional network pattern and intrinsic topologically disrupted in patients with anhedonia are related to SI. METHODS: The resting-fMRI by applying network-based statistic (NBS) and graph-theory analyses was estimated in 273 patients with MDD (144 high anhedonia [HA], 129 low anhedonia [LA]) and 150 healthy controls. In addition, we quantified the SI scores of each patient. Finally, the mediation analysis assessed whether anhedonia symptoms could mediate the relationship between anhedonia-related network metrics and SI. RESULT: The NBS analysis demonstrated that individuals with HA have a single abnormally increased functional connectivity component in a frontal-limbic circuit (termed the "anhedonia-related network", including the frontal cortex, striatum, anterior cingulate cortex and amygdala). The graph-theory analysis demonstrated that the anhedonia-related network showed a significantly disrupted topological organization (lower gamma and lambda), which the small-world property trend randomized. Furthermore, the anhedonia symptoms could mediate the relationship between the anhedonia-related network metrics (the mean functional connectivity values, the area under the curves values of gamma and nodal local efficiency in nucleus accumbens) and SI. CONCLUSIONS: We found that disruption of the reward-related network in MDD leads to SI through anhedonia symptoms. These findings show the abnormal topological construction of functional brain network organization in anhedonia, shedding light on the neurological processes underlying SI in MDD patients with anhedonia symptoms.

Application of molecular imprinting polymers in separation of active compounds from plants.

Molecular imprinting technique is becoming an appealing and prominent strategy to synthesize materials for target recognition and rapid separation. In recent years, it has been applied in separation of active compounds from various plants and has achieved satisfying results. This review aims to make a brief introduction of molecular imprinting polymers and their efficient application in the separation of various active components from plants, including flavonoids, organic acids, alkaloids, phenylpropanoids, anthraquinones, phenolics, terpenes, steroids, and diketones, which will provide some clues to help stimulating research into this fascinating and useful area.

New Attempts to Inhibit Methicillin-Resistant Staphylococcus aureus Biofilm? A Combination of Daptomycin and Azithromycin.

Objective: To investigate the antibacterial impact of daptomycin and azithromycin in vitro on methicillin-resistant Staphylococcus aureus (MRSA) biofilm. Methods: (1) Measure the strain growth curve and the biofilm formation curve. (2) Determine the minimum inhibitory concentrations (MICs) of daptomycin and azithromycin. (3) Investigate the antibacterial impact of the combination of daptomycin and azithromycin. (4) Perform the evaluation of the intervention impact of antimicrobial agents on MRSA biofilm. (5) Observe the biofilm after intervention with the antibacterial agent. Results: (1) MRSA exhibited three phases: lag phase (0-4 h), logarithmic growth (4-8 h) and stationary phase after 18 h; its biofilm began to form at 6 h, semi-matured at 24 h, and reached maturity after 48 h. (2) The MICs of daptomycin and azithromycin were 8 µg/mL and greater than 256 µg/mL, respectively. (3) The combination of daptomycin and azithromycin has an additive effect on MRSA (Fractional Inhibitory Concentration Index [FICI] 0.625) (FICI = MIC of drug A in combination/MIC of drug A alone + MIC of drug B in combination/MIC of drug B alone). Evaluation criteria: Synergistic effect is considered when FICI ≤ 0.5; additive effect is considered when 0.5 < FICI ≤ 1; irrelevant effect is considered when 1 < FICI ≤ 2; antagonistic effect is considered when FICI > 2). (4) Daptomycin or azithromycin at MICs inhibited not only the growth of planktonic bacteria but also the formation of biofilm. (5) The combination of both, in which group the ratio of live/dead bacteria is low and the biofilm morphology was incomplete, was more productive than monotherapy in against biofilm. Conclusion: Both daptomycin and azithromycin have anti-MRSA biofilm activity, and daptomycin is dominant. The fact that the combination of both can significantly inhibit the further maturation of MRSA biofilm and destroy already formed biofilm demonstrates the superiority of the combination over the monotherapy.

The sex differences in anhedonia in major depressive disorder: A resting-state fMRI study.

OBJECTIVE: The external behavioural manifestations and internal neural mechanisms of anhedonia are sexually dimorphic. This study aimed to explore the sex differences in the regional brain neuroimaging features of anhedonia in the context of major depressive disorder (MDD). METHOD: The resting-fMRI by applying amplitude of low-frequency fluctuation (ALFF) method was estimated in 414 patients with MDD (281 high anhedonia [HA], 133 low anhedonia [LA]) and 213 healthy controls (HC). The effects of two factors in patients with MDD were analysed using a 2 (sex: male, female) × 2 (group: HA, LA) ANOVA concerning the brain regions in which statistical differences were identified between patients with MDD and HC. We followed up with patients with HA at baseline, and 43 patients completed a second fMRI scan in remission. Paired t-test was performed to compare the ALFF values of anhedonia-related brain regions between the baseline and remission periods. RESULTS: For the sex-by-group interaction, the bilateral insula, right hippocampus, right post cingulum cortex, and left putamen showed significant differences. Furthermore, the abnormally elevated ALFF values in anhedonia-related brain regions at baseline decreased in remission. CONCLUSION: Our findings point to the fact that the females showed unique patterns of anhedonia-related brain activity compared to males, which may have clinical implications for interfering with the anhedonia symptoms in MDD. Using task fMRI, we can further examine the distinct characteristics between consumption anhedonia and anticipation anhedonia in MDD.