The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.

ABSTRACT: The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Change in Striatal Functional Connectivity Networks Across Two Years Due to Stimulant Exposure in Childhood ADHD: Results from the ABCD Sample.

Widely prescribed as the first choice of treatment for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (methylphenidate and amphetamines) have been studied for their long-term effects on the brain in prospective designs that carefully control dosage and adherence. It is unknown whether those findings generalize to real-world conditions such as community-based treatment, which is marked by intermittent exposure and polypharmacy. To fill this gap, we capitalized on the observational design of the Adolescent Brain Cognitive Development (ABCD) study to examine effects of stimulant exposure on modulation of large-scale bilateral cortical networks' resting-state functional connectivity (rs-FC) with 6 striatal regions (left and right caudate, putamen, and nucleus accumbens) across two years in children with ADHD. Out of 11,878 children, 179 met criteria for an ADHD diagnosis at baseline and high-quality imaging data at baseline and the two-year timepoint. Bayesian hierarchical logistic regressions revealed that change in rs-FC over the two-year period of multiple striatal-cortical networks associated with executive functions and a visuo-motor network predicted stimulant exposure. These networks did not overlap with those that predicted non-stimulant exposure. Of these networks, change selective to stimulant exposure was limited to rs-FC with the putamen, specifically frontoparietal and visual networks, implicating motor control. 23% of stimulant-exposed children did not meet criterion for ADHD at the two-year timepoint, and they were distinguished by change in rs-FC between left putamen and frontoparietal network. Thus, while stimulant exposure for a two-year period under real-world conditions modulated striatal-cortical functional networks broadly, therapeutic effects of that exposure were limited in scale, to network connections relevant to motor control in a small subset of children.

Spectroscopic Characterization of Highly Excited Neutral Chromium Tricarbonyl.

Spectroscopic characterization of highly excited neutral transition-metal complexes is important for understanding the multifaceted reaction mechanisms between metals and ligands. In this work, the reactions of neutral chromium atoms with carbon monoxide were probed by size-specific infrared spectroscopy. Interestingly, Cr(CO)3 was found to have an unprecedented 7A2″ septet excited state rather than the singlet ground state. A combination of experiment and theory shows that the gas-phase formation of this highly excited Cr(CO)3 is facile both thermodynamically and kinetically. Electronic structure and bonding analyses indicate that the valence electrons of Cr atoms in the septet Cr(CO)3 are in a relatively stable configuration, which facilitate the highly excited structure and the planar geometric shape (D3h symmetry). The observed septet Cr(CO)3 affords a paradigm for exploring the structure, properties, and formation mechanism of a large variety of excited neutral compounds.

Optimizing Antidepressant Efficacy: Multimodal Neuroimaging Biomarkers for Prediction of Treatment Response.

Major depressive disorder (MDD) is a common and often severe condition that profoundly diminishes quality of life for individuals across ages and demographic groups. Unfortunately, current antidepressant and psychotherapeutic treatments exhibit limited efficacy and unsatisfactory response rates in a substantial number of patients. The development of effective therapies for MDD is hindered by the insufficiently understood heterogeneity within the disorder and its elusive underlying mechanisms. To address these challenges, we present a target-oriented multimodal fusion framework that robustly predicts antidepressant response by integrating structural and functional connectivity data (sertraline: R 2 = 0.31; placebo: R 2 = 0.22). Through the model, we identify multimodal neuroimaging biomarkers of antidepressant response and observe that sertraline and placebo show distinct predictive patterns. We further decompose the overall predictive patterns into constitutive network constellations with generalizable structural-functional co-variation, which exhibit treatment-specific association with personality traits and behavioral/cognitive task performance. Our innovative and interpretable multimodal framework provides novel insights into the intricate neuropsychopharmacology of antidepressant treatment and paves the way for advances in precision medicine and development of more targeted antidepressant therapeutics. Trial Registration: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC), NCT#01407094.

So many measures in ERAS protocol: Which matters most?

OBJECTIVES: Enhanced recovery after surgery (ERAS), which includes multiple measures, has gradually become the standard perioperative management in pediatric surgery. However, it is still unclear which of its many measures affects the outcomes more. METHODS: We retrospectively analyzed the medical records of children with congenital choledochal cysts who underwent surgical treatment in a specialized children's hospital from January 2019 to December 2022. Data including baseline factors, implementation of ERAS interventions, postoperative complications, and postoperative length of stay (PLOS) were collected. Univariate and multivariate analyses were performed to identify the association between PLOS and baseline factors or specific ERAS measures. RESULTS: The implementation rate of ERAS measures ranged from 5.02% to 100% in 219 cases who underwent 3 to 14 ERAS measures. Univariate analysis showed that body mass index-for-age z-scores, liver function indicators, and postoperative complications were the significant baseline factors for PLOS. At the same time, the measures with the greatest effect on PLOS were early postoperative feeding and early removal of tubes. Multivariate analysis with different models revealed that postoperative complications, early postoperative feeding, and early catheter removal influenced the PLOS the most. CONCLUSIONS: A prolonged PLOS was associated with poor preoperative nutritional status, elevated liver function indexes, and postoperative complications. Early postoperative feeding and removal of tubes appeared more likely with a reduced PLOS than other measures, requiring more attention when implementing the ERAS protocol.

Anterior Segment Biometry During Accommodation After Posterior Chamber Phakic Implantable Collamer Lens Implantation.

PURPOSE: To evaluate the dynamic changes in anterior segment parameters during accommodation following Implantable Collamer Lens (ICL) implantation with swept-source optical coherence tomography (SS-OCT). METHODS: Under the accommodation of 0.00 diopters (D), 3.00 D, and maximum amplitude, SS-OCT was used to examine the anterior segment parameters, including ICL vault, ICL depth (the distance between the corneal endothelium and the posterior surface of ICL), crystalline lens thickness, anterior chamber depth, and various parameters of the anterior chamber angle, comprising angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle. RESULTS: During accommodation, the ICL vault showed a significant decrease from baseline (536 ± 278 µm) to 3.00 D (522 ± 281 µm), followed by an increase from 3.00 D to maximum amplitude (548 ± 306 µm) (analysis of variance [ANOVA], P < .001). Four eyes (2.61%) exhibited a decrease in ICL vault to less than 100 µm (47 ± 32 µm) at maximum accommodation. The ICL depth decreased significantly as accommodation increased (ANOVA, P < .001). Crystalline lens thickness increased, whereas anterior chamber depth decreased during accommodation (ANOVA, P < .001). The anterior chamber angle widened during 3.00 D of accommodation but narrowed at maximum accommodation, leading to significant changes in the angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle during accommodation (ANOVA, P < .001 for all). CONCLUSIONS: The anterior segment, including ICL vault and anterior chamber angle, undergo significant dynamic changes during accommodation. These accommodative changes may require careful monitoring for the surgery design of ICL implantation. [J Refract Surg. 2024;40(3):e164-e172.].

Spectroscopic and Theoretical Identifications of Two Structural Motifs of (H2O)10 Cluster.

Precise characterization of archetypal systems of aqueous hydrogen-bonding networks is essential for developing accurate potential functions and universal models of water. The structures of water clusters (H2O)n (n = 2-9) have been verified recently through size-specific infrared spectroscopy with a vacuum ultraviolet free electron laser (VUV-FEL) and quantum chemical studies. For (H2O)10, the pentagonal prism and butterfly motifs were proposed to be important building blocks and were observed in previous experiments. Here we report the size-specific infrared spectra of (H2O)10 via a joint experimental and theoretical study. Well-resolved spectra provide a unique signature for the coexistence of pentagonal prism and butterfly motifs. These (H2O)10 motifs develop from the dominant structures of (H2O)n (n = 8, 9) clusters. This work provides an intriguing prelude to the diverse structure of liquid water and opens avenues for size-dependent measurement of larger systems to understand the stepwise formation mechanism of hydrogen-bonding networks.

Metabolomics of human umbilical vein endothelial cell-based analysis of the relationship between hyperuricemia and dyslipidemia.

BACKGROUND AND AIMS: Hyperuricemia frequently accompanies dyslipidemia, yet the precise mechanism remains elusive. Leveraging cellular metabolomics analyses, this research probes the potential mechanisms wherein hyperuricemia provokes endothelial cell abnormalities, inducing disordered bile metabolism and resultant lipid anomalies. METHODS AND RESULTS: We aimed to identify the differential metabolite associated with lipid metabolism through adopting metabolomics approach, and thereafter adequately validating its protective function on HUVECs by using diverse assays to measure cellular viability, reactive oxygen species, migration potential, apoptosis and gene and protein levels of inflammatory factors. Taurochenodeoxycholic acid (TCDCA) (the differential metabolite of HUVECs) and the TCDCA-involved primary bile acid synthesis pathway were found to be negatively correlated with high UA levels based on the results of metabolomics analysis. It was noted that compared to the outcomes observed in UA-treated HUVECs, TCDCA could protect against UA-induced cellular damage and oxidative stress, increase proliferation as well as migration, and decreases apoptosis. In addition, it was observed that TCDCA might protect HUVECs by inhibiting UA-induced p38 mitogen-activated protein kinase/nuclear factor kappa-B p65 (p38MAPK/NF-κB p65) pathway gene and protein levels, as well as the levels of downstream inflammatory factors. CONCLUSION: The pathogenesis of hyperuricemia accompanying dyslipidemia may involve high uric acid levels eliciting inflammatory reactions and cellular damage in human umbilical vein endothelial cells (HUVECs), mediated through the p38MAPK/NF-κB signaling pathway, subsequently impinging on cellular bile acid synthesis and reducing bile acid production.

The learning curve of robot-assisted laparoscopic pyeloplasty in children.

To explore the learning curve of robot-assisted laparoscopic pyeloplasty (RALP) in children. The clinical data, surgical information, and postoperative complications of consecutive cases of RALP performed by the same surgeon in Shanghai Children's Hospital from January 2014 to July 2020 were retrospectively analyzed; the surgeon is a senior pediatric urologists who is proficient in laparoscopic pyeloplasty; the data consist of console time (CT), suture method when anastomosing ureteropelvic junction (UPJ), number of stitches (N), anastomosis time per stitch (tn), the average suture time per stitch (T) = (suture time of first stitch (t1) + second stitch (t2) + … + tn)/N, postoperative complications, and surgical outcome. The learning curve was depicted by cumulative sum method (CUSUM) and validated by cumulative method (CUM). Of the 88 cases, 64 cases were included in present study. Median CT was 104 (83-117) min, mean T was 109 ± 17 s. There were ten cases of Clavien-Dindo Grade I complication and two cases of Clavien-Dindo Grade IIIb complication. The median follow-up time was 237 (87-627) days. The learning curve of CT has three stages, with inflection points at 11th and 57th case, and T has two stages, with inflection points at 19th case. There was a statistically significant difference between the console time and length of stay on both sides of the inflection point (P < 0.05), but there was no statistically significant difference in age, gender, etiology, clinical manifestation, surgical outcome, and complication (P > 0.05). For a senior pediatric urologists who is proficient in laparoscopic pyeloplasty, the learning curve of RALP can be divided into three stages, preliminary exploration stage, mastery stage, and proficiency stage. It takes about 11 cases to achieve the mastery stage, and it takes about 57 cases to achieve the proficiency stage. The learning curve focused on the suture technique of the surgeon is divided into two stages, and after a learning period of 19 cases, it will reach the proficiency stage of suturing UPJ.

A pavement crack synthesis method based on conditional generative adversarial networks.

A Generative Adversarial Network (GAN) based asphalt pavement crack image generation method was proposed to improve the dataset size of the road images. Five open-source road crack datasets were leveraged to construct an image dataset, which contained two labels - transverse cracks and longitudinal cracks. The constructed dataset was used to facilitate crack detection and classification research by providing a diverse collection of labeled crack images derived from multiple public sources. The network structure of fully connected, convolutional and attention mechanisms based on the Conditional Generative Adversarial Network (CGAN) was used in this project. The purpose of this study was to train a generative model on selected categories of input pavement crack images and generate realistic crack images of those categories. We aim to tune the parameters of the GAN and optimize hyperparameters to improve the realism possibility of generated images. It also explored the generated images with different sizes and evaluated the performance of networks with different architectures. In particular, we analyzed the structural characteristics of conditional GAN. Results demonstrated that the Self-Attention Generative Adversarial Networks (SAGAN) model, which combines self-attention mechanisms with CGAN, can effectively address challenges related to limited crack image data and the inability to selectively generate images from specific categories. By conditioning the generator on category information, the SAGAN model was able to generate high-quality images while focusing on the target categories. Overall, the self-attention and conditional aspects of the SAGAN framework helped improve the generation of realistic pavement crack images.

Spatiotemporal Heterogeneity of Temperature and Catalytic Activation within Individual Catalyst Particles.

Temperature is a critical parameter in chemical conversion, significantly affecting the reaction kinetics and thermodynamics. Measuring temperature inside catalyst particles of industrial interest (∼micrometers to millimeters), which is crucial for understanding the evolution of chemical dynamics at catalytic active sites during reaction and advancing catalyst designs, however, remains a big challenge. Here, we propose an approach combining two-photon confocal microscopy and state-of-the-art upconversion luminescence (UL) imaging to measure the spatiotemporal-resolved temperature within individual catalyst particles in the industrially significant methanol-to-hydrocarbons reaction. Specifically, catalyst particles containing zeolites and functional nanothermometers were fabricated using microfluidic chips. Our experimental results directly demonstrate that the zeolite density and particle size can alter the temperature distribution within a single catalyst particle. Importantly, the observed temperature heterogeneity plays a decisive role in the activation of the reaction intermediate and the utilization of active sites. We expect that this work opens a venue for unveiling the reaction mechanism and kinetics within industrial catalyst particles by considering temperature heterogeneity.

Chinese expert consensus on the diagnosis, treatment, and management of asthma in women across life.

Background: The epidemiology and severity of asthma vary by sex and age. The diagnosis, treatment, and management of asthma in female patients are quite challenging. However, there is hitherto no comprehensive and standardized guidance for female patients with asthma. Methods: Corresponding search strategies were determined based on clinical concerns regarding female asthma. Search terms included "sex hormones and lung development", "sex hormone changes and asthma", "hormones and asthma immune response", "women, asthma", "children, asthma", "puberty, asthma", "menstruation, asthma", "pregnancy, asthma", "lactation, asthma", "menopause, asthma", "obesity, asthma", and "women, refractory, severe asthma". Literature was retrieved from PubMed/Medline, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Data with the search date of July 30, 2022 as the last day. This consensus used the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the strength of recommendation and quality of evidence. Results: We collected basic research results and clinical evidence-based medical data and reviewed the effects of sex hormones, classical genetics, and epigenetics on the clinical presentation and treatment response of female patients with asthma under different environmental effects. Based on that, we formulated this expert consensus on the management of female asthma throughout the life cycle. Conclusions: This expert consensus on the management of asthma in women throughout the life cycle provides diagnosis, treatment, and research reference for clinical and basic medical practitioners.

A convenient nomogram for predicting early death or liver transplantation after the Kasai procedure in patients with biliary atresia.

PURPOSE: Many patients with biliary atresia (BA) after the Kasai procedure (KP) progress to death or require liver transplantation to achieve long-term survival; however, most cases of death/liver transplantation (D/LT) occur in the early period after KP (usually within 1 year). This study was designed to construct a convenient nomogram for predicting early D/LT in patients with BA after KP. METHODS: A BA cohort was established in May 2017, and up to May 2023, 112 patients with 1-5 years of follow-up were enrolled in the study and randomly (ratio, 3:1) divided into a training cohort for constructing a nomogram (n = 84) and a validation cohort (n = 28) for externally validating the discrimination and calibration. The training cohort was divided into two groups: the early D/LT group (patients who died or had undergone LT within 1 year after KP [n = 35]) and the control group (patients who survived through the native liver more than 1 year after KP [n = 49]). Multivariate logistic regression and stepwise regression were applied to detect variables with the best predictive ability for the construction of the nomogram. The discrimination and calibration of the nomogram were internally and externally validated. RESULTS: The Kaplan-Meier (K-M) curve showed an actual 1-year native liver transplantation (NLS) rate of 57.1% and an estimated 2-year NLS rate of 55.2%. By multivariate regression and stepwise regression, age at KP, jaundice clearance (JC) speed 1 month after KP, early-onset PC (initial time < 36.5 days) after KP, sex, aspartate aminotransferase-to-platelet ratio index (APRI), and weight at KP were identified as the independent variables with the best ability to predict early D/LT and were used to construct a nomogram. The developed nomogram based on these independent variables showed relatively good discrimination and calibration according to internal and external validation. CONCLUSION: Most D/LTs were early D/LTs that occurred within 1 year after KP. The established nomogram based on predictors, including sex, weight at the KP, the APRI, age at the KP, JC speed 1 month after the KP, and early PC, may be useful for predicting early D/LT and may be helpful for counseling BA patients about patient prognosis after KP. This study was retrospectively registered at ClinicalTrials.gov (NCT05909033) in June 2023.

[Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes].

OBJECTIVE: To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation. METHODS: Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children's Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized. RESULTS: Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p.S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5. CONCLUSION: The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.

For the penile length-how shall we choose the straightening procedures in hypospadias repair?

OBJECTIVE: To define the appropriate penile straightening procedures corresponding to the specific penile curvature by comparing the penile length resulting from various straightening procedures in hypospadias repair. METHODS: We retrospectively analyzed hypospadias patients between 2017 and 2019. Patients were divided into three groups based on the penile curvature after degloving: <30°, 30°-45°, and >45°. The penile straightening procedures include dorsal plication (DP), simple urethral plate (UP) transection, and UP transection with ventral lengthening (VL). The paired t-test was conducted for the penile length after fully straightening in each group, simultaneously calculating the length changes (∆T). In addition, the penile length changes among these procedures were compared using Spearman analysis to show the correlation between the penile curvature and the length. RESULTS: The penile length changed significantly after fully straightening in all groups. The length decreased mildly after DP, while increased in the other procedures. The penile curvature after degloving was positively correlated with the absolute change in the penile length (P < 0.001, r = 0.424) and the ratio of ∆T in the original length (P < 0.001, r = 0.433). CONCLUSION: For hypospadias, the 30° after degloving may serve as the cut-off for the selection of the straightening method from the perspective of the penile length. For those with < 30°, methods such as DP or UP transection can either be selected. In patients with > 30°, DP should be used with caution because of the potential risk to shorten the penis. In contrast, UP transection effectively corrects the penile curvature and increases the penile length concurrently, which should be primarily recommended in those patients.

Photoelectron velocity map imaging spectroscopy of group 14 elements and iron tetracarbonyl anionic clusters MFe(CO)4- (M = Si, Ge, Sn).

The heteronuclear group 14 M-iron tetracarbonyl clusters MFe(CO)4- (M = Si, Ge, Sn) anions have been generated in the gas phase by laser ablation of M-Fe alloys and detected by mass and photoelectron spectroscopy. With the support of quantum chemical calculations, the geometric and electronic structures of MFe(CO)4- (M = Si, Ge, Sn) are elucidated, which shows that all the MFe(CO)4- clusters have the M-Fe bonded, iron-centered, and carbonyl-terminal M-Fe(CO)4 structure with the C2v symmetry and a 2B2 ground state. The M-Fe bond can be considered a double bond, which includes one σ electron sharing bond and one π dative bond. The C-O bonds in those anionic clusters are calculated to be elongated to different extents, and in particular, the C-O bonds in SiFe(CO)4- are elongated more. The Si-Fe alloy thus turns out to be a better collocation to activate the C-O bonds in the gas phase among group 14. The present findings have important implications for the rational development of high-performance catalysts with isolated metal atoms/clusters dispersed on supports.

Individual deviations from normative electroencephalographic connectivity predict antidepressant response.

BACKGROUND: Antidepressant medications yield unsatisfactory treatment outcomes in patients with major depressive disorder (MDD) with modest advantages over the placebo, partly due to the elusive mechanisms of antidepressant responses and unexplained heterogeneity in patient's response to treatment. Here we develop a novel normative modeling framework to quantify individual deviations in psychopathological dimensions that offers a promising avenue for the personalized treatment for psychiatric disorders. METHODS: We built a normative model with resting-state electroencephalography (EEG) connectivity data from healthy controls of three independent cohorts. We characterized the individual deviation of MDD patients from the healthy norms, based on which we trained sparse predictive models for treatment responses of MDD patients (102 sertraline-medicated and 119 placebo-medicated). Hamilton depression rating scale (HAMD-17) was assessed at both baseline and after the eight-week antidepressant treatment. RESULTS: We successfully predicted treatment outcomes for patients receiving sertraline (r = 0.43, p < 0.001) and placebo (r = 0.33, p < 0.001). We also showed that the normative modeling framework successfully distinguished subclinical and diagnostic variabilities among subjects. From the predictive models, we identified key connectivity signatures in resting-state EEG for antidepressant treatment, suggesting differences in neural circuit involvement between sertraline and placebo responses. CONCLUSIONS: Our findings and highly generalizable framework advance the neurobiological understanding in the potential pathways of antidepressant responses, enabling more targeted and effective personalized MDD treatment. TRIAL REGISTRATION: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC), NCT#01407094.

Oral microbiome associated with differential ratios of Porphyromonas gingivalis and Streptococcus cristatus.

Periodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis. To determine the role of S. cristatus in altering the interactions of P. gingivalis with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of S. cristatus and P. gingivalis. We then characterized the microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and compared the oral microbial composition and functional capabilities of the group with high S. cristatus-P. gingivalis ratios with the low ratio group. Taxonomic annotation revealed significant differences in the microbial composition at both the genus and species levels between the low and high S. cristatus-P. gingivalis ratio groups. Notably, a higher microbial diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. Furthermore, the antibiotic resistance gene profiles of the two groups were also distinct, with a significantly increased abundance of the genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios. It, therefore, indicates that the S. cristatus-P. gingivalis ratios influenced the virulence potential of the oral microbiome. Our work shows that enhancing the S. cristatus-P. gingivalis ratio in oral microbial communities can be an attractive approach for revising the dysbiotic oral microbiome.IMPORTANCEPeriodontitis, one of the most common chronic diseases, is linked to several systemic diseases, such as cardiovascular disease and diabetes. Although Porphyromonas gingivalis is a keystone pathogen that causes periodontitis, its levels, interactions with accessory bacteria and pathobionts in the oral microbiome, and its association with the pathogenic potential of the microbial communities are still not well understood. In this study, we revealed the role of Streptococcus cristatus and the ratios of S. cristatus and P. gingivalis in modulating the oral microbiome to facilitate a deeper understanding of periodontitis and its progression. The study has important clinical implications as it laid a foundation for developing novel non-antibiotic therapies against P. gingivalis and improving the efficiency of periodontal treatments.

Spectroscopic characterization of carbon monoxide activation by neutral chromium carbides.

Spectroscopic characterization of carbon monoxide activation by neutral metal carbides is of essential importance for understanding the structure-reactivity relationships of catalytic sites, but has been proven to be very challenging owing to the difficulty in size selection. Here, we report a size-specific infrared-vacuum ultraviolet spectroscopic study of the reactions between carbon monoxide with neutral chromium carbides. Quantum chemical calculations were carried out to identify the low-lying structures and to interpret the experimental features. The results reveal that the most stable structure of CrC3(CO)2 consists of a CCO ketenylidene unit and that of CrC4(CO)2 has a semi-bridging CO with a very low CO stretching vibrational frequency at 1821 cm-1. The electron structure analyses show that this semi-bridging CO is highly activated through the delocalized Cr-C-C three-center two-electron (3c-2e) interaction between the antibonding orbitals of CO and the metal carbide skeleton. The formation of these metal carbide carbonyls is found to be both thermodynamically exothermic and kinetically facile in the gas phase. The present findings have important implications for the mechanical understanding of the catalytic processes with isolated metal atoms/clusters dispersed on supports.