Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

The 5'UTR of HCoV-OC43 adopts a topologically constrained structure to intrinsically repress translation.

The emergence of SARS-CoV-2, which is responsible for the COVID-19 pandemic, has highlighted the need for rapid characterization of viral mechanisms associated with cellular pathogenesis. Viral UTRs represent conserved genomic elements that contribute to such mechanisms. Structural details of most CoV UTRs are not available, however. Experimental approaches are needed to allow for the facile generation of high-quality viral RNA tertiary structural models, which can facilitate comparative mechanistic efforts. By integrating experimental and computational techniques, we herein report the efficient characterization of conserved RNA structures within the 5'UTR of the HCoV-OC43 genome, a lab-tractable model coronavirus. We provide evidence that the 5'UTR folds into a structure with well-defined stem-loops (SLs) as determined by chemical probing and direct detection of hydrogen bonds by NMR. We combine experimental base-pair restraints with global structural information from SAXS to generate a 3D model that reveals that SL1-4 adopts a topologically constrained structure wherein SLs 3 and 4 coaxially stack. Coaxial stacking is mediated by short linker nucleotides and allows SLs 1 to 2 to sample different cojoint orientations by pivoting about the SL3,4 helical axis. To evaluate the functional relevance of the SL3,4 coaxial helix, we engineered luciferase reporter constructs harboring the HCoV-OC43 5'UTR with mutations designed to abrogate coaxial stacking. Our results reveal that the SL3,4 helix intrinsically represses translation efficiency since the destabilizing mutations correlate with increased luciferase expression relative to wildtype without affecting reporter mRNA levels, thus highlighting how the 5'UTR structure contributes to the viral mechanism.

All-Dielectric Integrated Meta-Antenna Operating in 6G Terahertz Communication Window.

Efficient transceivers and antennas at terahertz frequencies are leading the development of 6G terahertz communication systems. The antenna design for high-resolution terahertz spatial sensing and communication remains challenging, while emergent metallic metasurface antennas can address this issue but often suffer from low efficiency and complex manufacturing. Here, an all-dielectric integrated meta-antenna operating in 6G terahertz communication window for high-efficiency beam focusing in the sub-wavelength scale is reported. With the antenna surface functionalized by metagrating arrays with asymmetric scattering patterns, the design and optimization methods are demonstrated with a physical size constraint. The highest manipulation and diffraction efficiencies achieve 84.1% and 48.1%. The commercially accessible fabrication method with low cost and easy to implement has been demonstrated for the meta-antenna by photocuring 3D printing. A filamentous focal spot is measured as 0.86λ with a long depth of focus of 25.3λ. Its application for integrated imaging and communication has been demonstrated. The proposed technical roadmap provides a general pathway for creating high-efficiency integrated meta-antennas with great potential in high-resolution 6G terahertz spatial sensing and communication applications.

The relationship between male and female endogenous reproductive hormones levels and subjective cognitive decline score: A cross-sectional analysis of the Pingyin cohort study.

OBJECTIVE: Reproductive hormones might impact disease course in cognitive decline. We examined the association between male and female endogenous reproductive hormones and subjective cognitive decline (SCD) score. DESIGN, PATIENTS AND MEASUREMENTS: A cross-sectional study design was used with baseline data from the Pingyin cohort study, involving 1943 participants aged 45-70 years. Oestrogen (E2), testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured in females and E2 and testosterone were measured in males. We categorised hormones into three levels of low, intermediate and high level. The 9-item subjective cognitive decline questionnaire (SCD-Q9) scores were collected to assess the symptoms of SCD. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) between categorised hormone levels and SCD status. Multivariable linear regression models were also used. RESULTS: Overall, 1943 participants were involved and 1285 (66.1%) were female. The mean age at baseline was 59.1 (standard deviation 7.1) years. Women with high testosterone levels had a higher probability of having SCD compared with those with low testosterone levels (OR 1.43, 95% CI 1.01-2.05). Men with a high level of testosterone (0.59, 0.35-0.98) and high testosterone/E2 ratio (0.55, 0.33-0.90) were related to decreased chances of having SCD. Each one-unit increase of testosterone was linked to reduced SCD score in males [(ß: -.029, 95% CI (-0.052, -0.007)]. CONCLUSION: There was sex-specific relationship between hormone levels and SCD abnormal. Those with higher testosterone levels in females may increase likelihood of experiencing SCD. Males with higher testosterone levels and higher testosterone/E2 ratio may be associated with reduced likelihood of SCD. The roles of endogenous reproductive hormone levels and their dynamic changes in cognitive function need further investigation.

Red meat intake, faecal microbiome, serum trimethylamine N-oxide and hepatic steatosis among Chinese adults.

BACKGROUND AND AIMS: Emerging evidence suggests a detrimental impact of high red meat intake on hepatic steatosis. We investigated the potential interplay between red meat intake and gut microbiome on circulating levels of trimethylamine N-oxide (TMAO) and hepatic steatosis risk. METHODS: This cross-sectional study was conducted in a representative sample of 754 community-dwelling adults in Huoshan, China. Diet was collected using 4 quarterly 3 consecutive 24-h dietary (12-day) recalls. We profiled faecal microbiome using 16S ribosomal RNA sequencing and quantified serum TMAO and its precursors using LC-tandem MS (n = 333). We detected hepatic steatosis by FibroScan. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: TMAO levels but not its precursors were positively associated with the likelihood of hepatic steatosis (aOR per 1-SD increment 1.86, 95% CI 1.04-3.32). We identified 14 bacterial genera whose abundance was associated with TMAO concentration (pFDR < .05) belonging to the phyla Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria families. Per 10 g/day increase in red meat intake was positively associated with TMAO levels among participants who had higher red meat intake (>70 g/day) and higher TMAO-predicting microbial scores (TMS, ß = .045, p = .034), but not among others (pinteraction = .030). TMS significantly modified the positive association between red meat and steatosis (pinteraction = .032), with a stronger association being observed among participants with higher TMS (aOR 1.30, 95% CI 1.07-1.57). CONCLUSIONS: The bacterial genera that predicted TMAO levels may jointly modify the association between red meat intake and TMAO levels and the subsequent risk of hepatic steatosis.

Life course weight transitions from birth to childhood to midlife and risk of cardiovascular diseases and its subtypes.

BACKGROUND AND AIMS: Evidence on weight transitions across life stages and cardiovascular diseases (CVDs) is limited. We aimed to explore weight transition patterns from birth to childhood to midlife and risk of incident CVDs. METHODS: A total of 193,905 participants from the UK Biobank were included. Weight at birth, childhood, and midlife were collected at baseline (2006-2010). CVD outcomes were collected at year 2022. We constructed 27 transition patterns from birth to age 10 years to midlife. Cox proportional hazard models yielded hazard ratios (HRs) and 95% confidence intervals (CI) between weight transition patterns and CVDs. Mediation analyses were performed. Rate advancement periods (RAP) were also calculated. RESULTS: Several weight transition patterns were clearly linked to risk of CVDs, including "Low birth weight → high weight at age 10 years → obesity at midlife" (HR 2.64, 95% CI 2.24-3.11), "Low birth weight → low weight at age 10 years → obesity at midlife" (2.27, 1.93-2.66), "High birth weight → low weight at age 10 years → obesity at midlife" (2.29, 1.96-2.67), and "High birth weight → high weight at age 10 years → obesity at midlife" (2.14, 1.89-2.42), which showed even stronger association with HF. RAPs of these patterns were 8.3-10.6 years for CVD and 10.0-13.1 for HF. 50% of the association between birth weight and CVDs was mediated by weight at midlife. CONCLUSIONS: Our findings highlight the importance of weight management throughout the life course in reducing the risk of CVDs, especially maintaining a heathy weight at midlife.

Minor (≤ 10%) Ground-Glass Opacity Component in Clinical Stage I Non-Small Cell Lung Cancer: Associations With Pathologic Characteristics and Clinical Outcomes.

BACKGROUND. The presence of a ground-glass opacity (GGO) component is a favorable prognostic factor in non-small cell lung cancer (NSCLC), although the prognostic impact of a very small GGO component remains poorly investigated. OBJECTIVE. The purpose of this article is to investigate the impact of a minor (≤ 10%) GGO component on the prognosis of clinical stage I NSCLC in comparison with pure-solid nodules. METHODS. This retrospective study included 382 patients (mean age, 60.8 years; 210 men, 172 women) who underwent surgical resection between January 1, 2015, and December 31, 2015, for clinical stage I NSCLC appearing on preoperative chest CT as a nodule with a consolidation-to-tumor ratio (CTR) of 0.9 to 1.0. Two radiologists independently assigned nodules to groups as either minor GGO (CTR, ≥ 0.9 and < 1.0) or pure solid (CTR = 1.0). Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed by Kaplan-Meier curves and compared between groups using log-rank tests. Cox proportional hazards models were used to assess associations with outcomes. RESULTS. The two radiologists agreed for all nodules' classification into the minor-GGO (n = 106) or pure-solid (n = 276) groups. The mean CTR of the minor-GGO group was 0.93 ± 0.02 (SD) (range, 0.90-0.97). Minor-GGO nodules, in comparison with pure-solid nodules, showed greater solid-component diameter (2.68 vs 2.16 cm; p < .001) and total nodule diameter (2.89 vs 2.16 cm; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed lower frequencies of visceral pleural invasion (6.6% vs 17.0%, p = .009) and pathologic lymph node involvement (4.7% vs 20.3%, p < .001), and EGFR mutation (71.6% vs 39.9%; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed better 5-year RFS (83.4% vs 55.0%; p < .001) and higher frequency of better 5-year CSS (92.4% vs 76.4%, p = .004). In multivariable analysis adjusting for patient, imaging, pathologic, and genetic factors, a minor-GGO component was independently associated with a decreased likelihood of recurrence (HR = 0.37, p = .001) but not with the likelihood of CSS. CONCLUSION. Among patients with clinical stage I NSCLC, cancers with a minor-GGO component were associated with a better prognosis versus those with a pure-solid appearance. CLINICAL IMPACT. Radiologists encountering predominantly solid nodules on CT should carefully assess images for even a minor-GGO component given the favorable prognosis.

Swim bladder-derived biomaterials: structures, compositions, properties, modifications, and biomedical applications.

Animal-derived biomaterials have been extensively employed in clinical practice owing to their compositional and structural similarities with those of human tissues and organs, exhibiting good mechanical properties and biocompatibility, and extensive sources. However, there is an associated risk of infection with pathogenic microorganisms after the implantation of tissues from pigs, cattle, and other mammals in humans. Therefore, researchers have begun to explore the development of non-mammalian regenerative biomaterials. Among these is the swim bladder, a fish-derived biomaterial that is rapidly used in various fields of biomedicine because of its high collagen, elastin, and polysaccharide content. However, relevant reviews on the biomedical applications of swim bladders as effective biomaterials are lacking. Therefore, based on our previous research and in-depth understanding of this field, this review describes the structures and compositions, properties, and modifications of the swim bladder, with their direct (including soft tissue repair, dural repair, cardiovascular repair, and edible and pharmaceutical fish maw) and indirect applications (including extracted collagen peptides with smaller molecular weights, and collagen or gelatin with higher molecular weights used for hydrogels, and biological adhesives or glues) in the field of biomedicine in recent years. This review provides insights into the use of swim bladders as source of biomaterial; hence, it can aid biomedicine scholars by providing directions for advancements in this field.

Gut microbiota, skin microbiota, and alopecia areata: A Mendelian randomization study.

BACKGROUND: Observational studies have shown an association between skin microbiota and alopecia areata (AA), but the causal connection remains ambiguous. METHODS: We obtained data on skin microbiota and AA from summary statistics of Genome-Wide Association Studies and applied statistical methods from Mendelian randomization (MR) to assess causal relationships. Additionally, we investigated whether the skin microbiota acts as a mediator in the pathway from gut microbiota to AA. RESULTS: In the MR analysis of KORA FF4 and AA, the inverse-variance weighting method indicated that Corynebacterium (odds ratio [OR] = 0.82, 95% confidence interval [CI]: 0.70-0.96, p = 0.02) and asv037 (OR = 0.87, 95% CI: 0.76-0.99, p = 0.05) exerted protective effects, while Betaproteobacteria (OR = 1.21, 95% CI: 1.01-1.44, p = 0.03), asv015 (OR = 1.27, 95% CI: 1.05-1.54, p = 0.02), and Burkholderiales (OR = 1.20, 95% CI: 1.04-1.38, p = 0.01) were identified as risk factors in AA. In the MR analysis of PopGen and AA, asv001 (OR = 1.12, 95% CI: 1.01-1.24, p = 0.04), asv054 (OR = 1.13, 95% CI: 1.01-1.25, p = 0.03), and asv059 (OR = 1.14, 95% CI: 1.02-1.27, p = 0.02) were found to potentially increase the risk in AA. Furthermore, in the influence of gut microbiota on AA, the skin microbiota did not act as a mediator. CONCLUSION: Our analysis suggests potential causal relationships between certain skin microbiota and AA, revealing insights into its pathogenesis and potential intervention strategies.

Deep learning reconstruction for coronary CT angiography in patients with origin anomaly, stent or bypass graft.

PURPOSE: To develop and validate a deep learning (DL)-model for automatic reconstruction for coronary CT angiography (CCTA) in patients with origin anomaly, stent or bypass graft. MATERIAL AND METHODS: In this retrospective study, a DL model for automatic CCTA reconstruction was developed with training and validation sets from 6063 and 1962 patients. The algorithm was evaluated on an independent external test set of 812 patients (357 with origin anomaly or revascularization, 455 without). The image quality of DL reconstruction and manual reconstruction (using dedicated cardiac reconstruction software provided by CT vendors) was compared using a 5-point scale. The successful reconstruction rates and post-processing time for two methods were recorded. RESULTS: In the external test set, 812 patients (mean age, 64.0 ± 11.6, 100 with origin anomalies, 152 with stents, 105 with bypass grafts) were evaluated. The successful rates for automatic reconstruction were 100% (455/455), 97% (97/100), 100% (152/152), and 76.2% (80/105) in patients with native vessel, origin anomaly, stent, and bypass graft, respectively. The image quality scores were significantly higher for DL reconstruction than those for manual approach in all subgroups (4 vs. 3 for native vessel, 4 vs. 4 for origin anomaly, 4 vs. 3 for stent and 4 vs. 3 for bypass graft, all p < 0.001). The overall post-processing time was remarkably reduced for DL reconstruction compared to manual method (11 s vs. 465 s, p < 0.001). CONCLUSIONS: The developed DL model enabled accurate automatic CCTA reconstruction of bypass graft, stent and origin anomaly. It significantly reduced post-processing time and improved clinical workflow.

An Ultrathin Flexible Programmable Spin Logic Device Based on Spin-Orbit Torque.

Flexible electronic devices have shown increasingly promising value facilitating our daily lives. However, flexible spintronic devices remain in their infancy. Here, this research demonstrates a type of nonvolatile, low power dissipation, and programmable flexible spin logic device, which is based on the spin-orbit torque in polyimide (PI)/Ta/Pt/Co/Pt heterostructures fabricated via capillary-assisted electrochemical delamination. The magnetization switching ratio is shown to be about 50% for the flexible device and does not change after 100 cycles of bending, indicating the device has stable performance. By designing the path of pulse current, five Boolean logic gates AND, NAND, NOT, NOR, and OR can be realized in an integrated two-element device. Moreover, such peeling-off devices can be successfully transferred to almost any substrate, such as paper and human skin, and maintain high performance. The flexible PI/Ta/Pt/Co/Pt spin logic device serves as logic-in-memory architecture and can be used in wearable electronics.

Highly Selective Production of C2+ Oxygenates from CO2 in Strongly Acidic Condition by Rough Ag-Cu Electrocatalyst.

The acidic electrocatalytic conversion of CO2 to multi-carbon (C2+) oxygenates is of great importance in view of enhancing carbon utilization efficiency and generating products with high energy densities, but suffering from low selectivity and activity. Herein, we synthesized Ag-Cu alloy catalyst with highly rough surface, by which the selectivity to C2+ oxygenates can be greatly improved. In a strongly acidic condition (pH=0.75), the maximum C2+ products Faradaic efficiency (FE) and C2+ oxygenates FE reach 80.4 % and 56.5 % at -1.9 V versus reversible hydrogen electrode, respectively, with a ratio of FEC2+ oxygenates to FEethylene up to 2.36. At this condition, the C2+ oxygenates partial current density is as high as 480 mA cm-2. The in situ spectra, control experiments and theoretical calculations indicate that the high generation of C2+ oxygenates over the catalyst originates from its large surface roughness and Ag alloying.

Synthesis of n-Propanol from CO2 Electroreduction on Bicontinuous Cu2O/Cu Nanodomains.

n-propanol is an important pharmaceutical and pesticide intermediate. To produce n-propanol by electrochemical reduction of CO2 is a promising way, but is largely restricted by the very low selectivity and activity. How to promote the coupling of *C1 and *C2 intermediates to form the *C3 intermediate for n-propanol formation is challenging. Here, we propose the construction of bicontinuous structure of Cu2O/Cu electrocatalyst, which consists of ultra-small Cu2O nanodomains, Cu nanodomains and large amounts of grain boundaries between Cu2O and Cu nanodomains. The n-propanol current density is as high as 101.6 mA cm-2 at the applied potential of -1.1 V vs. reversible hydrogen electrode in flow cell, with the Faradaic efficiency up to 12.1 %. Moreover, the catalyst keeps relatively stable during electrochemical CO2 reduction process. Experimental studies and theoretical calculations reveal that the bicontinuous structure of Cu2O/Cu can facilitate the *CO formation, *CO-*CO coupling and *CO-*OCCO coupling for the final generation of n-propanol.

The RNA-binding protein AUF1 facilitates Akt phosphorylation at the membrane.

Mammalian target of rapamycin (mTOR), which is part of mTOR complex 1 (mTORC1) and mTORC2, controls cellular metabolism in response to levels of nutrients and other growth signals. A hallmark of mTORC2 activation is the phosphorylation of Akt, which becomes upregulated in cancer. How mTORC2 modulates Akt phosphorylation remains poorly understood. Here, we found that the RNA-binding protein, AUF1 (ARE/poly(U)-binding/degradation factor 1), modulates mTORC2/Akt signaling. We determined that AUF1 is required for phosphorylation of Akt at Thr308, Thr450, and Ser473 and that AUF1 also mediates phosphorylation of the mTORC2-modulated metabolic enzyme glutamine fructose-6-phosphate amidotransferase 1 at Ser243. In addition, AUF1 immunoprecipitation followed by quantitative RT-PCR revealed that the mRNAs of Akt, glutamine fructose-6-phosphate amidotransferase 1, and the mTORC2 component SIN1 associate with AUF1. Furthermore, expression of the p40 and p45, but not the p37 or p42, isoforms of AUF1 specifically mediate Akt phosphorylation. In the absence of AUF1, subcellular fractionation indicated that Akt fails to localize to the membrane. However, ectopic expression of a membrane-targeted allele of Akt is sufficient to allow Akt-Ser473 phosphorylation despite AUF1 depletion. Finally, conditions that enhance mTORC2 signaling, such as acute glutamine withdrawal, augment AUF1 phosphorylation, whereas mTOR inhibition abolishes AUF1 phosphorylation. Our findings unravel a role for AUF1 in promoting membrane localization of Akt to facilitate its phosphorylation on this cellular compartment. Targeting AUF1 could have therapeutic benefit for cancers with upregulated mTORC2/Akt signaling.

Deep Learning Segmentation and Reconstruction for CT of Chronic Total Coronary Occlusion.

Background CT imaging of chronic total occlusion (CTO) is useful in guiding revascularization, but manual reconstruction and quantification are time consuming. Purpose To develop and validate a deep learning (DL) model for automated CTO reconstruction. Materials and Methods In this retrospective study, a DL model for automated CTO segmentation and reconstruction was developed using coronary CT angiography images from a training set of 6066 patients (582 with CTO, 5484 without CTO) and a validation set of 1962 patients (208 with CTO, 1754 without CTO). The algorithm was validated using an external test set of 211 patients with CTO. The consistency and measurement agreement of CTO quantification were compared between the DL model and the conventional manual protocol using the intraclass correlation coefficient, Cohen κ coefficient, and Bland-Altman plot. The predictive values of CT-derived Multicenter CTO Registry of Japan (J-CTO) score for revascularization success were evaluated. Results In the external test set, 211 patients (mean age, 66 years ± 11 [SD]; 164 men) with 240 CTO lesions were evaluated. Automated segmentation and reconstruction of CTOs by DL was successful in 95% of lesions (228 of 240) without manual editing and in 48% of lesions (116 of 240) with the conventional manual protocol (P < .001). The total postprocessing and measurement time was shorter for DL than for manual reconstruction (mean, 121 seconds ± 20 vs 456 seconds ± 68; P < .001). The quantitative and qualitative CTO parameters evaluated with the two methods showed excellent correlation (all correlation coefficients > 0.85, all P < .001) and minimal measurement difference. The predictive values of J-CTO score derived from DL and conventional manual quantification for procedure success showed no difference (area under the receiver operating characteristic curve, 0.76 [95% CI: 0.69, 0.82] and 0.76 [95% CI: 0.69, 0.82], respectively; P = .55). Conclusion When compared with manual reconstruction, the deep learning model considerably reduced postprocessing time for chronic total occlusion quantification and had excellent correlation and agreement in the anatomic assessment of occlusion features. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Loewe in this issue.

Hepatectomy After Conversion Therapy Using Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy for Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: Combined treatment with tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies showed high anti-tumor efficacy and made conversion resection possible for patients with unresectable hepatocellular carcinoma (HCC). However, long-term survival has not been reported. METHODS: A cohort of consecutive patients who received combined TKI/anti-PD-1 antibodies as first-line treatment for initially unresectable HCC at the authors' hospital between August 2018 and September 2020 was eligible for this study. Patients who were responding to systemic therapy and met the criteria for hepatectomy underwent liver resection with curative intention. The study also investigated the association of clinical factors with successful conversion resection and postoperative recurrence. RESULTS: The study enrolled 101 patients including 24 patients (23.8 %) who underwent R0 resection a median of 3.9 months (interquartile range: 2.5-5.9 months) after initiation of systemic therapy. Patients with an Eastern cooperative oncology group performance status of 0, fewer intrahepatic tumors, or a radiographic response to systemic therapy were more likely to be able to receive curative resection. After a median follow-up period of 21.5 months, hepatectomy was independently associated with a favorable overall survival (hazard ratio [HR], 0.050; 95 % confidence interval [CI], 0.007-0.365; P = 0.003). For the 24 patients who underwent surgery, the 12-month recurrence-free survival and overall survival rates were respectively 75% and 95.8%. Achieving a pathologic complete response (n = 10) to systemic therapy was associated with a favorable recurrence-free survival after resection, with a trend toward significance (HR, 0.345; 95% CI, 0.067-1.785; P = 0.187). CONCLUSIONS: Selected patients with initially unresectable HCC can undergo hepatectomy after systemic therapy with combined TKI/anti-PD-1 antibodies. In this study, conversion resection was associated with a favorable prognosis.

Brain structural abnormalities in adult major depressive disorder revealed by voxel- and source-based morphometry: evidence from the REST-meta-MDD Consortium.

BACKGROUND: Neuroimaging studies on major depressive disorder (MDD) have identified an extensive range of brain structural abnormalities, but the exact neural mechanisms associated with MDD remain elusive. Most previous studies were performed with voxel- or surface-based morphometry which were univariate methods without considering spatial information across voxels/vertices. METHODS: Brain morphology was investigated using voxel-based morphometry (VBM) and source-based morphometry (SBM) in 1082 MDD patients and 990 healthy controls (HCs) from the REST-meta-MDD Consortium. We first examined group differences in regional grey matter (GM) volumes and structural covariance networks between patients and HCs. We then compared first-episode, drug-naïve (FEDN) patients, and recurrent patients. Additionally, we assessed the effects of symptom severity and illness duration on brain alterations. RESULTS: VBM showed decreased GM volume in various regions in MDD patients including the superior temporal cortex, anterior and middle cingulate cortex, inferior frontal cortex, and precuneus. SBM returned differences only in the prefrontal network. Comparisons between FEDN and recurrent MDD patients showed no significant differences by VBM, but SBM showed greater decreases in prefrontal, basal ganglia, visual, and cerebellar networks in the recurrent group. Moreover, depression severity was associated with volumes in the inferior frontal gyrus and precuneus, as well as the prefrontal network. CONCLUSIONS: Simultaneous application of VBM and SBM methods revealed brain alterations in MDD patients and specified differences between recurrent and FEDN patients, which tentatively provide an effective multivariate method to identify potential neurobiological markers for depression.

Maternal RNA binding protein with multiple splicing 2 (RBPMS2) is involved in mouse blastocyst formation through the bone morphogenetic protein pathway.

RESEARCH QUESTION: Is early embryo development in mice influenced by RNA binding protein with multiple splicing 2 (RBPMS2), a maternal factor that accumulates and is stored in the cytoplasm of mature oocytes? DESIGN: The expression patterns of RBPMS2 in mouse were analysed using quantitative real-time PCR (qRT PCR) and immunofluorescence staining. The effect of knockdown of RBPMS2 on embryo development was evaluated through a microinjection of specific morpholino or small interfering RNA. RNA sequencing was performed for mechanistic analysis. The interaction between RBPMS2 and the bone morphogenetic protein (BMP) pathway was studied using BMP inhibitor and activator. The effect on the localization of E-cadherin was determined by immunofluorescence staining. RESULTS: Maternal protein RBPMS2 is highly expressed in mouse oocytes, and knockdown of RBPMS2 inhibits embryo development from the morula to the blastocyst stage. Mechanistically, RNA sequencing showed that the differentially expressed genes were enriched in the transforming growth factor-ß (TGF-ß) signalling pathway. BMPs are members of the TGF-ß superfamily of growth factors. It was found that the addition of BMP inhibitor to the culture medium led to a morula-stage arrest, similar to that seen in RBPMS2 knockdown embryos. This morula-stage arrest defect caused by RBPMS2 knockdown was partially rescued by BMP activator. Furthermore, the localization of E-cadherin to the membrane was impaired in response to a knockdown of RBPMS2 or inhibition of the BMP pathway. CONCLUSION: This study suggests that RBPMS2 activates the BMP pathway and thus influences the localization of E-cadherin, which is important for early mouse embryo development during blastocyst formation.

Healthy and unhealthy low-carbohydrate diets and plasma markers of cardiometabolic risk.

Previous studies have reported inconsistent associations between low-carbohydrate diets (LCD) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCD in cardiometabolic health. We investigated the cross-sectional associations between LCD and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasising unsaturated fat, plant protein and less low-quality carbohydrates) and unhealthy (emphasising saturated fat, animal protein and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34 785 participants aged 18-85 years were included. After adjusting for covariates including BMI, healthy LCD was associated with lower levels of insulin, homoeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP) and TAG, and higher levels of HDL-cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of -5·91, -6·16, -9·13, -9·71 and 7·60 (all Ptrend < 0·001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP and LDL-cholesterol (all Ptrend < 0·001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies.

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study.

The association between time-restricted eating (TRE) and the risk of non-alcoholic fatty liver disease (NAFLD) is less studied. Moreover, whether the association is independent of physical exercise or diet quality or quantity is uncertain. In this nationwide cross-sectional study of 3813 participants, the timing of food intakes was recorded by 24-h recalls; NAFLD was defined through vibration-controlled transient elastography in the absence of other causes of chronic liver disease. OR and 95 % CI were estimated using logistic regression. Participants with daily eating window of ≤ 8 h had lower odds of NAFLD (OR = 0·70, 95 % CI: 0·52, 0·93), compared with those with ≥ 10 h window. Early (05.00-15.00) and late TRE (11.00-21.00) showed inverse associations with NAFLD prevalence without statistical heterogeneity (Pheterogeneity = 0·649) with OR of 0·73 (95 % CI: 0·36, 1·47) and 0·61 (95 % CI: 0·44, 0·84), respectively. Such inverse association seemed stronger in participants with lower energy intake (OR = 0·58, 95 % CI: 0·38, 0·89, Pinteraction = 0·020). There are no statistical differences in the TRE-NAFLD associations according to physical activity (Pinteraction = 0·390) or diet quality (Pinteraction = 0·110). TRE might be associated with lower likelihood of NAFLD. Such inverse association is independent of physical activity and diet quality and appears stronger in individuals consuming lower energy. Given the potential misclassification of TRE based on one- or two-day recall in the analysis, epidemiological studies with validated methods for measuring the habitual timing of dietary intake are warranted.