Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis.

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

PCK2 maintains intestinal homeostasis and prevents colitis by protecting antibody-secreting cells from oxidative stress.

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.

Mechanism of Salvia miltiorrhiza Bunge extract to alleviate Chronic Sleep Deprivation-Induced cognitive dysfunction in rats.

BACKGROUND: Bidirectional communication between the gut microbiota and the brain may play an essential role in the cognitive dysfunction associated with chronic sleep deprivation(CSD). Salvia miltiorrhiza Bunge (Danshen, DS), a famous Chinese medicine and functional tea, is extensively used to protect learning and memory capacities, although the mechanism of action remains unknown. PURPOSE: The purpose of this research was to explore the efficacy and the underlying mechanism of DS in cognitive dysfunction caused by CSD. METHODS: DS chemical composition was analyzed by UPLC-QTOF-MS/MS. Forty rats were randomly assigned to five groups (n = 8): control (CON), model (MOD), low- (1.35 g/kg, DSL), high-dose (2.70 g/kg, DSH) DS group, and Melatonin(100 mg/kg, MT) group. A CSD rat model was established over 21 days. DS's effects and the underlying mechanism were explored using the open-field test(OFT), Morris water-maze(MWM), tissue staining(Hematoxylin and Eosin Staining, Nissl staining, Alcian blue-periodic acid SCHIFF staining, and Immunofluorescence), enzyme-linked immunosorbent assay, Western blot, quantitative real-time polymerase chain reaction(qPCR), and 16S rRNA sequencing. RESULTS: We demonstrated that CSD caused gut dysbiosis and cognitive dysfunction. Furthermore, 16S rRNA sequencing demonstrated that Firmicutes and Proteobacteria were more in fecal samples from model group rats, whereas Bacteroidota and Spirochaetota were less. DS therapy, on the contrary hand, greatly restored the gut microbial community, consequently alleviating cognitive impairment in rats. Further research revealed that DS administration reduced systemic inflammation via lowering intestinal inflammation and barrier disruption. Following that, DS therapy reduced Blood Brain Barrier(BBB) and neuronal damage, further decreasing neuroinflammation in the hippocampus(HP). Mechanistic studies revealed that DS therapy lowered lipopolysaccharide (LPS) levels in the HP, serum, and colon, consequently blocking the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products(IL-1ß, IL-6, TNF-α, iNOS, and COX2) in the HP and colon. CONCLUSION: DS treatment dramatically improved spatial learning and memory impairments in rats with CSD by regulating the composition of the intestinal flora, preserving gut and brain barrier function, and reducing inflammation mediated by the LPS-TLR4 signaling pathway. Our findings provide novel insight into the mechanisms by which DS treats cognitive dysfunction caused by CSD.

SOC bioavailability significantly correlated with the microbial activity mediated by size fractionation and soil morphology in agricultural ecosystems.

Despite the fact that physical and chemical processes have been widely proposed to explicate the stabilization mechanisms of soil organic carbon (SOC), thebioavailability of SOC linked to soil physical structure, microbial community structure, and functional genes remains poorly understood. This study aims to investigate the SOC division based on bioavailability differences formed by physical isolation, and to clarify the relationships of SOC bioavailability with soil elements, pore characteristics, and microbial activity. Results revealed that soil element abundances such as SOC, TN, and DOC ranked in the same order as the soil porosity as clay > silt ≥ coarse sand > fine sand in both top and sub soil. In contrast to silt and clay, which had reduced SOC bioavailability, fine sand and coarse sand had dramatically enhanced SOC bioavailability compared to the bulk soil. The bacterial and fungal community structure was significantly influenced by particle size, porosity, and soil elements. Copiotrophic bacteria and functional genes were more prevalent in fine sand than clay, which also contained more oligotrophic bacteria. The SOC bioavailability was positively correlated with abundances of functional genes, C degradation genes, and copiotrophic bacteria, but negatively correlated with abundances of soil elements, porosity, oligotrophic bacteria, and microbial biomass (p < 0.05). This indicated that the soil physical structure divided SOC into pools with varying levels of bioavailability, with sand fractions having more bioavailable organic carbon than finer fractions. Copiotrophic Proteobacteria and oligotrophic Acidobacteria, Firmicutes, and Gemmatimonadetes made up the majority of the bacteria linked to SOC mineralization. Additionally, the fungi Mortierellomycota and Mucoromycota, which are mostly involved in SOC mineralization, may have the potential for oligotrophic metabolism. Our results indicated that particle-size fractionation could influence the SOC bioavailability by restricting SOC accessibility and microbial activity, thus having a significant impact on sustaining soil organic carbon reserves in temperate agricultural ecosystems, and provided a new research direction for organic carbon stability.

Therapeutic effects of finasteride: inhibition of disease progression and serum prostate-specific antigen reduction in patients with prostatic intraepithelial neoplasia.

The objective of this study was to evaluate the impact of finasteride on the progression of prostate intraepithelial neoplasia and levels of prostate-specific antigen (PSA) in patients. A total of 120 patients with high-grade prostatic intraepithelial neoplasia were included in this study from January 2013 to January 2018. All patients underwent prostate biopsies. Among them, 60 patients were assigned to the observation group and received a daily dosage of 5 mg finasteride for 60 months, while the remaining 60 patients were assigned to the control group and did not receive finasteride. PSA levels were measured every six months, and imaging scans were conducted throughout the five-year study period. Additional biopsies were performed if PSA levels exceeded 10 ng/mL or imaging suggested the presence of prostate cancer. Statistical analysis was applied to the collected data. In total, 25 cases of prostate cancer were identified in this study. Of these cases, 7 patients belonged to the observation group, whereas the remaining 18 patients were from the control group. The observation group exhibited significantly lower levels of total serum PSA (p < 0.001) and Gleason scores (p < 0.001) compared to the control group. Our study, which involved 120 participants, demonstrated that finasteride effectively reduces serum PSA levels and mitigates the severity of prostate cancer. These findings suggest that finasteride holds potential as a treatment option for patients with -high-grade prostatic intraepithelial neoplasia.

Deep Learning-Based Reconstruction Improves the Image Quality of Low-Dose CT Colonography.

RATIONALE AND OBJECTIVES: To evaluate the image quality of low-dose CT colonography (CTC) using deep learning-based reconstruction (DLR) compared to iterative reconstruction (IR). MATERIALS AND METHODS: Adults included in the study were divided into four groups according to body mass index (BMI). Routine-dose (RD: 120 kVp) CTC images were reconstructed with IR (RD-IR); low-dose (LD: 100kVp) images were reconstructed with IR (LD-IR) and DLR (LD-DLR). The subjective image quality was rated on a 5-point scale by two radiologists independently. The parameters for objective image quality included noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The Friedman test was used to compare the image quality among RD-IR, LD-IR and LD-DLR. The KruskalWallis test was used to compare the results among different BMI groups. RESULTS: A total of 270 volunteers (mean age: 47.94 years ± 11.57; 115 men) were included. The effective dose of low-dose CTC was decreased by approximately 83.18% (5.18mSv ± 0.86 vs. 0.86mSv ± 0.05, P < 0.001). The subjective image quality score of LD-DLR was superior to that of LD-IR (3.61 ± 0.56 vs. 2.70 ± 0.51, P < 0.001) and on par with the RD- IR's (3.61 ± 0.56 vs. 3.74 ± 0.52, P = 0.486). LD-DLR exhibited the lowest noise, and the maximum SNR and CNR compared to RD-IR and LD-IR (all P < 0.001). No statistical difference was found in the noise of LD-DLR images between different BMI groups (all P > 0.05). CONCLUSION: Compared to IR, DLR provided low-dose CTC with superior image quality at an average radiation dose of 0.86mSv, which may be promising in future colorectal cancer screening.

Adsorption of Pb(II) by UV-aged microplastics and cotransport in homogeneous and heterogeneous porous media.

To investigate the adsorption effects of aged microplastics (MPs) on Pb(II) and their co-transport properties in homogeneous (quartz sand) and heterogeneous (quartz sand with apple branches biochar) porous media, we explored the co-transport of UV-irradiated aged MPs and coexisting Pb(II) along with their interaction mechanisms. The UV aging process increased the binding sites and electronegativity of the aged MPs' surface, enhancing its adsorption capacity for Pb(II). Aged MPs significantly improved Pb(II) transport through homogeneous media, while Pb(II) hindered the transport of aged MPs by reducing electrostatic repulsion between these particles and the quartz sand. When biochar, with its loose and porous structure, was used as a porous medium, it effectively inhibited the transport capacity of both contaminants. In addition, since the aged MPs cannot penetrate the column, a portion of Pb(II) adsorbed by the aged MPs will be co-deposited with the aged MPs, hindering Pb(II) transport to a greater extent. The transport experiments were simulated and interpreted using two-point kinetic modeling and the DLVO theory. The study results elucidate disparities in the capacity of MPs and aged MPs to transport Pb(II), underscoring the potential of biochar application as an effective strategy to impede the dispersion of composite environmental pollutants.

Comparison of Diatrizoate and Iohexol for Patient Acceptance and Fecal-Tagging Performance in Noncathartic CT Colonography.

OBJECTIVE: The aim of this study was to compare diatrizoate and iohexol regarding patient acceptance and fecal-tagging performance in noncathartic computed tomography colonography. METHODS: This study enrolled 284 volunteers with fecal tagging by either diatrizoate or iohexol at an iodine concentration of 13.33 mg/mL and an iodine load of 24 g. Patient acceptance was rated on a 4-point scale of gastrointestinal discomfort. Two gastrointestinal radiologists jointly analyzed image quality, fecal-tagging density and homogeneity, and residual contrast agent in the small intestine. The results were compared by the generalized estimating equation method. RESULTS: Patient acceptance was comparable between the 2 groups (3.95 ± 0.22 vs 3.96 ± 0.20, P = 0.777). The diatrizoate group had less residual fluid and stool than the iohexol group ( P = 0.019, P = 0.004, respectively). There was no significant difference in colorectal distention, residual fluid, and stool tagging quality between the 2 groups (all P 's > 0.05). The mean 2-dimensional image quality score was 4.59 ± 0.68 with diatrizoate and 3.60 ± 1.14 with iohexol ( P < 0.001). The attenuation of tagged feces was 581 ± 66 HU with diatrizoate and 1038 ± 117 HU with iohexol ( P < 0.001). Residual contrast agent in the small intestine was assessed at 55.3% and 62.3% for the diatrizoate group and iohexol group, respectively ( P = 0.003). CONCLUSIONS: Compared with iohexol, diatrizoate had better image quality, proper fecal-tagging density, and more homogeneous tagging along with comparable excellent patient acceptance, and might be more suitable for fecal tagging in noncathartic computed tomography colonography.

Integrative single-cell analysis reveals distinct adaptive immune signatures in the cutaneous lesions of pemphigus.

Pemphigus, an autoimmune bullous disease affecting the skin and mucosal membranes, is primarily driven by anti-desmoglein (Dsg) autoantibodies. However, the underlying immune mechanisms of this disease remain largely elusive. Here, we compile an unbiased atlas of immune cells in pemphigus cutaneous lesions at single-cell resolution. We reveal clonally expanded antibody-secreting cells (ASCs) that exhibit variable hypermutation and accumulation of IgG4 class-switching in their immunoglobulin genes. Importantly, pathogenic Dsg-specific ASCs are localized within pemphigus lesions and can evolve from both Dsg-autoreactive and non-binding precursors. We observe an altered distribution of CD4+ T cell subsets within pemphigus lesions, including an imbalance of Th17/Th2 cells. Significantly, we identify a distinct subpopulation of Th17 cells expressing CXCL13 and IL-21 within pemphigus lesions, implying its pivotal role in B cell recruitment and local production of autoantibodies. Furthermore, we characterize multiple clonally expanded CD8+ subpopulations, including effector GMZB+ and GMZK+ subsets with augmented cytotoxic activities, within pemphigus lesions. Chemokine-receptor mapping uncovers cell-type-specific signaling programs involved in the recruitment of T/B cells within pemphigus lesions. Our findings significantly contribute to advancing the understanding of the heterogeneous immune microenvironment and the pathogenesis of pemphigus cutaneous lesions, thereby providing valuable insights for potential therapeutic interventions in this disease.

Mn-Anti-CTLA4-CREKA-Sericin Nanotheragnostics for Enhanced Magnetic Resonance Imaging and Tumor Immunotherapy.

The integration of magnetic resonance imaging (MRI), cGAS-STING, and anti-CTLA-4 (aCTLA-4) based immunotherapy offers new opportunities for tumor precision therapy. However, the precise delivery of aCTLA-4 and manganese (Mn), an activator of cGAS, to tumors remains a major challenge for enhanced MRI and active immunotherapy. Herein, a theragnostic nanosphere Mn-CREKA-aCTLA-4-SS (MCCS) is prepared by covalently assembling Mn2+, silk sericin (SS), pentapeptide CREKA, and aCTLA-4. MCCS are stable with an average size of 160 nm and is almost negatively charged or neutral at pH 5.5/7.4. T1-weighted images showed MCCS actively targeted tumors to improve the relaxation rate r1 and contrast time of MRI. This studies demonstrated MCCS raises reactive oxygen species levels, activates the cGAS-STING pathway, stimulates effectors CD8+ and CD80+ T cells, reduces regulatory T cell numbers, and increases IFN-γ and granzyme secretion, thereby inducing tumor cells autophagy and apoptosis in vitro and in vivo. Also, MCCS are biocompatible and biosafe. These studies show the great potential of Mn-/SS-based integrative material MCCS for precision and personalized tumor nanotheragnostics.

LARP1 senses free ribosomes to coordinate supply and demand of ribosomal proteins.

Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies implicate LARP1 in 40S- or 80S-ribosome complexes that repress and stabilize TOPs. However, a mechanistic understanding of how LARP1 and TOPs interact with these complexes to coordinate TOP outcomes is lacking. Here, we show that LARP1 senses the cellular supply of ribosomes by directly binding non-translating ribosomal subunits. Cryo-EM structures reveal a previously uncharacterized domain of LARP1 bound to and occluding the 40S mRNA channel. Free cytosolic ribosomes induce sequestration of TOPs in repressed 80S-LARP1-TOP complexes independent of alterations in mTOR signaling. Together, this work demonstrates a general ribosome-sensing function of LARP1 that allows it to tune ribosome protein synthesis to cellular demand.

Neural Correlates of Anhedonia in Major Depressive Disorder: Insights from Concurrent Analysis of Feedback-Related Negativity and Stimulus-Preceding Negativity.

Purpose: Anhedonia, a core symptom of major depressive disorder (MDD), is explored in this study, focusing on the neural underpinnings through the examination of two event-related potential (ERP) components: feedback-related negativity (FRN) and stimulus-preceding negativity (SPN). Patients and Methods: This cross-sectional study was conducted in China from March 2022 to March 2023. It involved 35 MDD patients and 31 healthy controls (HC) participating in a modified 2-door task with simultaneous EEG recordings. Depression severity and anhedonia were assessed using the Hamilton Depression Scale (HAMD) and the Temporal Experience of Pleasure Scale (TEPS-CV), respectively. FRN and SPN metrics, along with correlations with each other and clinical assessments, were examined. Results: In comparison to the HC group, the MDD group exhibited significantly lower scores in TEPS-CV (t = 2.854, p = 0.006) and its subscales (t = -3.596, p = 0.001 and t = 2.434, p = 0.018, respectively), along with consistently reduced amplitudes of FRN (F 1.64= 4.726, p = 0.033) and SPN (F 1.64= 4.195, p = 0.045) across all conditions. Limited correlations were observed between ERP metrics and clinical indicators, except for positive correlations between FRN amplitudes (loss minus win) and HAMD scores (r = 0.392, p = 0.020), and SPN amplitudes after losing (SPN-L) and TEPS-CV consumption subscale scores (r = 0.357, p = 0.035). Notably, while the HC group displayed no significant FRN-SPN correlations, the MDD group exhibited positive FRN-SPN correlations under distinct conditions (r = 0.376, p = 0.026 and r = 0.355, p = 0.037, respectively). Conclusion: Our data reveal subjective and objective anhedonia in both consumption and anticipation, suggesting a shared impairment in reward feedback processing and anticipatory neural mechanisms in individuals with MDD. These findings deepen our understanding of anhedonia's neural foundations and may guide targeted interventions for this core symptom.

Ketamine Promoted Breast Cancer Invasion and Metastasis Through Up-regulating Wnt, BMP, and EGFR Signaling.

BACKGROUND/AIM: In this study, we used an orthotropic breast cancer model combined with ketamine addiction and next-generation sequencing (NGS) to comprehensively investigate molecular alterations in ketamine-mediated metastasis. Ketamine is widely used in anesthesia and drug abuse. Our previous study revealed that ketamine promotes the growth of breast cancer cells; however, the detailed molecular mechanism remains unknown. MATERIALS AND METHODS: An orthotropic breast cancer model was established by injecting EO771 breast cancer cells into the mammary fat pad of mice intraperitoneally administered ketamine (30 mg/kg, daily) for 68 days. Tumors collected at day 38 were frozen for future analysis, and their metastasis state was checked at day 68. RESULTS: Tumors were grouped and subjected to NGS analysis, followed by differential gene expression analysis (DEseq) and pathway identification. DEseq analysis showed that ketamine up-regulated metastasis-related signaling, and the key genes were BMP5, FZD6, MMP1B, EGFR, WNT5A, BMP7, and DCN. CONCLUSION: Ketamine addiction up-regulates the expression of genes involved in the Wnt, EGFR, and BMP signaling cascades, which may be associated with breast cancer progression and metastasis.

Identifying the pathophysiological traits of obstructive sleep apnea during dexmedetomidine sedation.

Dexmedetomidine (DEX) has been described as a safe sedative in clinical practice, but its effects on the pathophysiological traits of obstructive sleep apnea (OSA) are unclear. We estimated the effects of DEX sedation on the four key pathophysiological traits of OSA (pharyngeal collapsibility, dilator muscle function, arousal threshold, and loop gain) in adult patients with OSA by conducting a secondary analysis of a prospective diagnostic trial. Pathophysiological traits estimated from polysomnography and the respiratory parameters under natural sleep and DEX-induced sleep were compared. Bivariate and multivariate linear regression analyses were used to estimate the relationship between pathophysiological traits and OSA severity for both sleep states. Adult patients with OSA had a significantly higher pharyngeal collapsibility (Vpassive : 44.9 [15.7 to 53.8] vs. 53.3 [34.2 to 66.3] %eupnea , p < 0.001), arousal threshold (178.5 [132.5 to 234.6] vs. 140.5 [123.2 to 192.3] %eupnea , p < 0.001), and loop gain (LG1: 0.74 ± 0.25 vs. 0.60 ± 0.17, p < 0.001; LGn: 0.52 ± 0.12 vs. 0.44 ± 0.08, p < 0.001) during DEX-induced sleep compared with natural sleep. There was no significant difference in dilator muscle function or PSG respiratory parameters between natural versus DEX-induced sleep states. Bivariate regression analysis showed varying degrees of correlation between OSA traits and severity. Multiple regression analysis indicated that collapsibility was the strongest predictor of the apnea-hypopnea index for both sleep states. Dexmedetomidine sedation in patients with OSA increased the pharyngeal collapsibility without impairing dilator muscle function, while elevating arousal threshold and increasing loop gain.

The Neural Correlates of the Social Perception Dysfunction in Schizophrenia: An fMRI Study.

Purpose: Patients with schizophrenia show deficits in facial emotion recognition and emotional intensity assessment, and also exhibit structural and functional irregularities in specific brain regions. In this study, we aimed to examine differences in active brain regions involved in processing the Emotion Intensity Recognition Task (EIRT), which can serve as an indicator of emotion recognition and ability to perceive intensity, between patients with schizophrenia and healthy controls (HCs). The purpose of this study was to investigate dysfunctional brain regions and investigate the role of the amygdala in social cognition deficits in patients with schizophrenia by focusing on alterations in amygdala activity linked to facial emotion recognition. Participants and Methods: Twenty-two patients who met a diagnostic criteria for schizophrenia according to DSM-IV and 27 HCs participated in an MRI scan while completing the EIRT. Behavioral and MRI data were collected and analyzed. Results: Behavioral results showed that patients with schizophrenia made significantly more errors in recognizing surprise, happiness, sadness, fear, and neutral expressions, and patients with schizophrenia exhibited significantly slower response times in recognizing happy facial expressions. Imaging results showed that schizophrenia patients found hypoactivation in several inferior parietal and temporal regions, in the cerebrum and anterior cingulate; and decreased amygdala activation in individuals with schizophrenia was associated with impaired recognition of fear in facial expressions. Conclusion: Facial emotion processing deficits are emotion-specific (surprise, happiness, sadness, fear, and neutral expressions) in schizophrenia. Hypoactivation in several inferior parietal and temporal regions, in the cerebrum and anterior cingulate, was thought to contribute to symptom formation in schizophrenia. Reduction in amygdala activation in schizophrenia patients was associated with impairment of the fear-emotional process.

Decreased beta 1 (12-15 Hertz) power modulates the transfer of suicidal ideation to suicide in major depressive disorder.

BACKGROUND: Suicide prevention for major depressive disorder (MDD) is a worldwide challenge, especially for suicide attempt (SA). Viewing suicide as a state rather than a lifetime event provided new perspectives on suicide research. OBJECTIVE: This study aimed to verify and complement SAs biomarkers of MDD with a recent SA sample. METHODS: This study included 189 participants (60 healthy controls; 47 MDD patients with non-suicide (MDD-NSs), 40 MDD patients with suicide ideation (MDD-SIs) and 42 MDD patients with SA (MDD-SAs)). MDD patients with an acute SA time was determined to be within 1 week since the last SA. SUICIDALITY Part in MINI was applied to evaluate suicidality. Absolute powers in 14 frequency bands were extracted from subject's resting-state electroencephalography data and compared within four groups. The relationship among suicidality, the number of SA and powers in significant frequency bands were investigated. RESULTS: MDD-SIs had increased powers in delta, theta, alpha and beta band on the right frontocentral channels compared to MDD-NSs, while MDD-SAs had decreased powers in delta, beta and gamma bands on widely the right frontocentral and parietooccipital channels compared to MDD-SIs. Beta 1 power was the lowest in MDD-SAs and was modulated by the number of SA. The correlation between suicidality and beta 1 power was negative in MDD-SAs and positive in MDD-SIs. CONCLUSION: Reduced beta 1 (12-15 Hz) power could be essential in promoting suicidal behaviour in MDD. Research on recent SA samples contributes to a better understanding of suicide mechanisms and preventing suicidal behaviour in MDD.

Mechanism of 5S RNP recruitment and helicase-surveilled rRNA maturation during pre-60S biogenesis.

Ribosome biogenesis proceeds along a multifaceted pathway from the nucleolus to the cytoplasm that is extensively coupled to several quality control mechanisms. However, the mode by which 5S ribosomal RNA is incorporated into the developing pre-60S ribosome, which in humans links ribosome biogenesis to cell proliferation by surveillance by factors such as p53-MDM2, is poorly understood. Here, we report nine nucleolar pre-60S cryo-EM structures from Chaetomium thermophilum, one of which clarifies the mechanism of 5S RNP incorporation into the early pre-60S. Successive assembly states then represent how helicases Dbp10 and Spb4, and the Pumilio domain factor Puf6 act in series to surveil the gradual folding of the nearby 25S rRNA domain IV. Finally, the methyltransferase Spb1 methylates a universally conserved guanine nucleotide in the A-loop of the peptidyl transferase center, thereby licensing further maturation. Our findings provide insight into the hierarchical action of helicases in safeguarding rRNA tertiary structure folding and coupling to surveillance mechanisms that culminate in local RNA modification.

Laser coupling in waterjets subject to jet instabilities, laser parameters, and alignment errors.

High coupling accuracy and efficiency attract wide attention in waterjet-guided laser technology due to the requirements for high processing performance in hard-to-cut material and diamond industries. The behaviors of axisymmetric waterjets injected into the atmosphere through different types of orifices are investigated by adopting a two-phase flow k-epsilon algorithm. The water-gas interface is tracked with Coupled Level Set and Volume of Fluid method. The electric field distributions of laser radiation inside the coupling unit are modeled by wave equations and numerically solved with the full-wave Finite Element Method. The coupling efficiency of the laser beam affected by waterjet hydrodynamics is studied by considering the profiles of the waterjet shaped at transient stages, namely vena contracta, cavitation, and hydraulic flip. The growth of the cavity leads to a larger water-air interface and increases the coupling efficiency. Eventually, two types of fully developed laminar waterjets, i.e. constricted waterjets and non-constricted waterjets, are formed. Constricted waterjets that are detached from the wall throughout the nozzle are preferable to guide laser beams since they significantly increase the coupling efficiency compared to non-constricted waterjets. Furthermore, the trends of coupling efficiency affected by Numerical Aperture (NA), wavelengths, and alignments errors are analyzed to optimize the physical design of the coupling unit and develop the alignment strategies.

The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response.

Pathogens and inflammatory conditions rapidly induce the expression of immune-responsive gene 1 (IRG1) in cells of myeloid lineage. IRG1 encodes an aconitate decarboxylase (ACOD1) that produces the immunomodulatory metabolite itaconate (ITA). In addition to rapid intracellular accumulation, ITA is also secreted from the cell, but whether secreted ITA functions as a signaling molecule is unclear. Here, we identified ITA as an orthosteric agonist of the GPCR OXGR1, with an EC50 of approximately 0.3 mM, which was in the same range as the physiological concentration of extracellular ITA upon macrophage activation. ITA activated OXGR1 to induce Ca2+ mobilization, ERK phosphorylation, and endocytosis of the receptor. In a mouse model of pulmonary infection with bacterial Pseudomonas aeruginosa, ITA stimulated Oxgr1-dependent mucus secretion and transport in respiratory epithelium, the primary innate defense mechanism of the airway. Our study thus identifies ITA as a bona fide ligand for OXGR1 and the ITA/OXGR1 paracrine signaling pathway during the pulmonary innate immune response.