Two-dimensional halide perovskite lateral epitaxial heterostructures.

Epitaxial heterostructures based on oxide perovskites and III-V, II-VI and transition metal dichalcogenide semiconductors form the foundation of modern electronics and optoelectronics1-7. Halide perovskites-an emerging family of tunable semiconductors with desirable properties-are attractive for applications such as solution-processed solar cells, light-emitting diodes, detectors and lasers8-15. Their inherently soft crystal lattice allows greater tolerance to lattice mismatch, making them promising for heterostructure formation and semiconductor integration16,17. Atomically sharp epitaxial interfaces are necessary to improve performance and for device miniaturization. However, epitaxial growth of atomically sharp heterostructures of halide perovskites has not yet been achieved, owing to their high intrinsic ion mobility, which leads to interdiffusion and large junction widths18-21, and owing to their poor chemical stability, which leads to decomposition of prior layers during the fabrication of subsequent layers. Therefore, understanding the origins of this instability and identifying effective approaches to suppress ion diffusion are of great importance22-26. Here we report an effective strategy to substantially inhibit in-plane ion diffusion in two-dimensional halide perovskites by incorporating rigid π-conjugated organic ligands. We demonstrate highly stable and tunable lateral epitaxial heterostructures, multiheterostructures and superlattices. Near-atomically sharp interfaces and epitaxial growth are revealed by low-dose aberration-corrected high-resolution transmission electron microscopy. Molecular dynamics simulations confirm the reduced heterostructure disorder and larger vacancy formation energies of the two-dimensional perovskites in the presence of conjugated ligands. These findings provide insights into the immobilization and stabilization of halide perovskite semiconductors and demonstrate a materials platform for complex and molecularly thin superlattices, devices and integrated circuits.

Superior Phonon-Limited Exciton Mobility in Lead-Free Two-Dimensional Perovskites.

Tin-based two-dimensional (2D) perovskites are emerging as lead-free alternatives in halide perovskite materials, yet their exciton dynamics and transport remain less understood due to defect scattering. Addressing this, we employed temperature-dependent transient photoluminescence (PL) microscopy to investigate intrinsic exciton transport in three structurally analogous Sn- and Pb-based 2D perovskites. Employing conjugated ligands, we synthesized high-quality crystals with enhanced phase stability at various temperatures. Our results revealed phonon-limited exciton transport in Sn perovskites, with diffusion constants increasing from 0.2 cm2 s-1 at room temperature to 0.6 cm2 s-1 at 40 K, and a narrowing PL line width. Notably, Sn-based perovskites exhibited greater exciton mobility than their Pb-based equivalents, which is attributed to lighter effective masses. Thermally activated optical phonon scattering was observed in Sn-based compounds but was absent in Pb-based materials. These findings, supported by molecular dynamics simulations, demonstrate that the phonon scattering mechanism in Sn-based halide perovskites can be distinct from their Pb counterparts.

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.

The role of the immune system in early-onset schizophrenia: identifying immune characteristic genes and cells from peripheral blood.

BACKGROUND: Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology. METHODS: We obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm. RESULTS: We selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7. CONCLUSION: Our results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.

Plasma levels of hydrogen sulfide and homocysteine correlate with the efficacy of antidepressant agents and serve as potential diagnostic and therapeutic markers.

OBJECTIVE: Hydrogen sulfide (H2S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H2S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function. METHODS: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H2S and Hcy, and data were correlated to determine their potential as plasma biomarkers. RESULTS: Cross-sectional analyses revealed PSDs to have a low plasma H2S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H2S and Hcy in PSDs. Plasma levels of H2S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H2S and Hcy and expression of the TNF gene (i.e., H2S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents. CONCLUSION: Plasma levels of H2S and Hcy reflect changes in psychopathology and cognitive function in depression and H2S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.

Asparagine reduces the risk of schizophrenia: a bidirectional two-sample mendelian randomization study of aspartate, asparagine and schizophrenia.

BACKGROUND: Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. METHODS: This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. RESULTS: No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483-3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987-1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999-1.011, P-value = 0.132). CONCLUSION: This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Analysis of morphology, histology characteristics, and circadian clock gene expression of Onychostoma macrolepis at the overwintering period and the breeding period.

Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.

IL-1ß/IL-1R1 signaling is involved in the propagation of α-synuclein pathology of the gastrointestinal tract to the brain.

The pathological hallmark of Parkinson's disease (PD) is the intraneuronal accumulation of misfolded alpha-synuclein (termed Lewy bodies) in dopaminergic neurons of substantia nigra par compacta (SNc). It is assumed that the α-syn pathology is induced by gastrointestinal inflammation and then transfers to the brain by the gut-brain axis. Therefore, the relationship between gastrointestinal inflammation and α-syn pathology leading to PD remains to be investigated. In our study, rotenone (ROT) oral administration induces gastrointestinal tract (GIT) inflammation in mice. In addition, we used pseudorabies virus (PRV) for tracing studies and performed behavioral testing. We observed that ROT treatments enhance macrophage activation, inflammatory mediator expression, and α-syn pathology in the GIT 6-week post-treatment (P6). Moreover, pathological α-syn was localized with IL-1R1 positive neural cells in GIT. In line with these findings, we also find pS129-α-syn signals in the dorsal motor nucleus of the vagus (DMV) and tyrosine hydroxylase in the nigral-striatum dynamically change from 3-week post-treatment (P3) to P6. Following that, pS129-α-syn was dominant in the enteric neural cell, DMV, and SNc, accompanied by microglial activation, and these phenotypes were absent in IL-1R1r/r mice. These data suggest that IL-1ß/IL-1R1-dependent inflammation of GIT can induce α-syn pathology, which then propagates to the DMV and SNc, resulting in PD.

Self-Cleaning Recyclable Multiplexed Photoelectrochemical Sensing Strategy Based on Exonuclease III-Assisted Signal Discrimination.

For discriminating the signals of multi-targets, multiplexed photoelectrochemical (PEC) detection is generally accomplished by modulating the light source or voltage, which prospect is usually limited by expensive instrumentation, tedious operational steps, and time-consuming material screening. To realize multiplexed determination on single photoelectric interface using the routine technique, a non-instrument-assisted strategy for signal discrimination needs to be explored. Herein, we propose an exonuclease III-mediated multiple PEC signals resolution strategy and construct a self-cleaning recyclable multiplexed PEC sensor using a porphyrin-bipyridine-based covalent organic framework (Por-Bpy COF) photocathode. Specifically, following the dual-target recognition event, exonuclease III cleaves the DNA strand attached to the magnetic bead so that the two signal labels can be separated. Once the signal label binds to the DNA on the electrode surface (E-DNA), exonuclease III turns to excise the DNA strand of the signal label and consequently the E-DNA can repeatedly bind different signal labels. As a result, distinguishable photocurrent signals of different targets can be generated on a single photoelectric interface. The feasibility of this multiplexed sensor is verified by detecting two coexisting mycotoxins aflatoxin B1 and zearalenone. On account of eliminating the instrumentation constraints and simplifying the experimental procedures, the proposed sensing strategy may provide a brand-new idea for the exploration of portable multiplexed PEC sensing devices.

Sodium Incorporation for Performance Improvement of Solution-Processed Submicron CuIn(S,Se)2 Thin Film Solar Cells.

Low-cost solution-processed CuIn(S,Se)2 (CISSe) has great potential for large-scale production of photovoltaics (PV). However, low power conversion efficiency caused by poor crystallinity is one of the main drawbacks compared to vacuum-processed CISSe solar cells. In this work, three strategies for sodium (Na) incorporation into solution-processed CISSe by soaking in sodium chloride (NaCl) aqueous-ethanol solution [1 molarity (M) for 10 minutes (min)], either prior to absorber deposition (pre-deposition treatment, Pre-DT), before selenization (pre-selenization treatment, Pre-ST), or after selenization (post-selenization treatment, PST) are researched. The Pre-ST CISSe solar cells achieve a better PV performance than those from the other two strategies of Na incorporation. For optimization, soaking times (5, 10, and 15 min) and NaCl concentrations (from 0.2 to 1.2 m) of the Pre-ST are researched. The highest efficiency achieved is 9.6% with an open-circuit voltage (Voc ) of 464.5 mV, a short-circuit current density (jsc ) of 33.4 mA cm-2 , and a fill factor (FF) of 62.0%. Compared to the reference CISSe solar cell, Voc , jsc , FF, and efficiency of the champion Pre-ST CISSe device are improved absolutely by 61.0 mV, 6.5 mA cm-2 , 9%, and 3.8%, respectively. Simultaneously, the open-circuit voltage deficit, the back contact barrier, and the bulk recombination are found to be reduced for Pre-ST CISSe.

Plasma exosomes lncRNA-miRNA-mRNA network construction and its diagnostic efficacy identification in first-episode schizophrenia.

BACKGROUND: The exosomal lncRNA-miRNA-mRNA networks in first episode schizophrenia (FOS) have not reported yet. This study examined the lncRNA, miRNA and mRNA expression level in exosome derived from first episode schizophrenia (FOS) patients, and explored the the potential of exosomes as biomarkers for schizophrenia. METHODS: We recruited 10 FOS patients and healthy controls (HCs) respectively, examined the lncRNA, miRNA and mRNA expression level of plasma exosome by high throughput sequencing, constructed lncRNA-miRNA-mRNA network, and performed correlation analysis, GO and KEGG pathway analysis, PPI network construction and ROC analysis. RESULTS: There were 746 differently expressed lncRNA, 22 differently expressed miRNA, and 2637 differently expressed mRNA in plasma exosome in FOS compared with HCs. Then we constructed ceRNA network consisting of 8 down-regulated lncRNA, 7 up-regulated miRNA and 65 down-regulated mRNA, and 1 up-regulated lncRNA, 1 down-regulated miRNA and 4 up-regulated mRNA. The expression level of 1 lncRNA and 7 mRNA in exosomal network were correlated with PANSS score. GO and KEGG pathway analysis showed that 4 up-regulated mRNAs were enriched in neuropsychiatric system function. Down-regulated mRNA EZH2 and SIRT1 were identified as hub gene. Finally, we detected the ROC curve of ENSG00000251562, miR-26a-5p, EZH2, miR-22-3p, SIRT1, ENSG00000251562-miR-26a-5p-EZH2, ENSG00000251562-miR-22-3p-SIRT1, and found that the AUC of ceRNA network was higher than lncRNA, miRNA and mRNA alone. CONCLUSION: We constructed the lncRNA-miRNA-mRNA network in exosome derived from FOS plasma, and found that lncRNA-miRNA-mRNA network has potential as biomarkers for FOS.

Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways.

INTRODUCTION: Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. METHODS: Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. RESULTS: The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3ß and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3ß and FoxO3a were upregulated. CONCLUSIONS: Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

Reticular Chemistry-Enabled Sonodynamic Activity of Covalent Organic Frameworks for Nanodynamic Cancer Therapy.

The development of covalent organic framework (COF) sonosensitizers with intrinsic sonodynamic effects is highly desirable. However, such COFs are generally constructed using small-molecule photosensitizers. Herein, we report that the reticular chemistry-based synthesis of COFs from two inert monomers yields a COF-based sonosensitizer (TPE-NN) with inherent sonodynamic activity. Subsequently, a nanoscale COF TPE-NN is fabricated and embedded with copper (Cu)-coordinated sites to obtain TPE-NN-Cu. Results show that Cu coordination can enhance the sonodynamic effect of TPE-NN, whereas ultrasound (US) irradiation for sonodynamic therapy can augment the chemodynamic efficacy of TPE-NN-Cu. Consequently, TPE-NN-Cu upon US irradiation shows high-performance anticancer effects based on mutually reinforced sono-/chemo-nanodynamic therapy. This study reveals the backbone-originated sonodynamic activity of COFs and proposes a paradigm of intrinsic COF sonosensitizers for nanodynamic therapy.

Stable Isotope-Resolved Metabolomics Studies on Corticosteroid-Induced PC12 Cells: A Strategy for Evaluating Glucose Catabolism in an in Vitro Model of Depression.

Depression is a common psychopathological state or mood disorder syndrome. The serious risks to human life and the inadequacy of the existing antidepressant drugs have driven us to understand the pathogenesis of depression from a new perspective. Our research group has found disturbances in glucose catabolism in both depression and nephrotic syndrome. What are the specific metabolic pathways and specificities of glucose catabolism disorders caused by depression? To address the above scientific questions, we creatively combined traditional metabolomics technology with stable isotope-resolved metabolomics to research the glucose catabolism of the corticosterone-induced PC12 cell damage model and the adriamycin-induced glomerular podocyte damage model. The results showed an increased flux of pyruvate metabolism in depression. The increased flux of pyruvate metabolism led to an activation of gluconeogenesis in depression. The disturbed upstream metabolism of succinate caused the tricarboxylic acid cycle (TCA cycle) to be blocked in depression. In addition, there were metabolic disturbances in the purine metabolism and pentose phosphate pathways in depression. Compared with nephrotic syndrome, pyruvate metabolism, the TCA cycle, and gluconeogenesis metabolism in depression were specific. The metabolic pathways researched above are likely to be important targets for the efficacy of antidepressants.

Exerkine apelin reverses obesity-associated placental dysfunction by accelerating mitochondrial biogenesis in mice.

Maternal exercise (ME) protects against adverse effects of maternal obesity (MO) on fetal development. As a cytokine stimulated by exercise, apelin (APN) is elevated due to ME, but its roles in mediating the effects of ME on placental development remain to be defined. Two studies were conducted. In the first study, 18 female mice were assigned to control (CON), obesogenic diet (OB), or OB with exercise (OB/Ex) groups (n = 6); in the second study, the same number of female mice were assigned to three groups; CON with PBS injection (CD/PBS), OB/PBS, or OB with apelin injection (OB/APN). In the exercise study, daily treadmill exercise during pregnancy significantly elevated the expression of PR domain 16 (PRDM16; P < 0.001), which correlated with enhanced oxidative metabolism and mitochondrial biogenesis in the placenta (P < 0.05). More importantly, these changes were partially mirrored in the apelin study. Apelin administration upregulated PRDM16 protein level (P < 0.001), mitochondrial biogenesis (P < 0.05), placental nutrient transporter expression (P < 0.001), and placental vascularization (P < 0.01), which were impaired due to MO (P < 0.05). In summary, MO impairs oxidative phosphorylation in the placenta, which is improved by ME; apelin administration partially mimics the beneficial effects of exercise on improving placental function, which prevents placental dysfunction due to MO.NEW & NOTEWORTHY Maternal exercise prevents metabolic disorders of mothers and offspring induced by high-fat diet. Exercise intervention enhances PRDM16 activation, oxidative metabolism, and vascularization of placenta, which are inhibited due to maternal obesity. Similar to maternal exercise, apelin administration improves placental function of obese dams.

Switchable Multiplex Photoelectrochemical Immunoassay of Aß42 and Aß40 Based on a pH-Responsive i-Motif Probe and Pyrene-Based MOF Photocathode.

In accurately diagnosing Alzheimer's disease (AD) and distinguishing AD from other dementia, the concentration ratio of amyloid-beta 42 (Aß42) to Aß40 is more reliable than the concentration of Aß42 alone. For the multiplex PEC assay, generating an independent photocurrent of multiple targets on a single interface is a great challenge. Herein, an i-motif-based switchable sensing approach is proposed to construct a pH-regulated multiplex PEC immunosensor for Aß42 and Aß40 by using Bi-TBAPy as an efficient photoactive cathode material. An independent photocurrent signal of Aß42 and Aß40 is produced through the regulation of the electron-transfer tunneling distance by a pH-dependent configuration transition of the i-motif DNA. In a 96-well plate, immunological recognition of Aß42 (or Aß40) coupled with an enzymatic catalytic reaction produces an acidic (or alkaline) lysis solution, which triggers the formation and unravelment of the i-motif structure. The above configuration transition regulates the distance between Au NPs labeled SH-DNA and Bi-TBAPy, leading to PEC signal switching. Smart integration of the pH-responsive switchable DNA probe with a high-efficiency photocathode enables the precise monitoring of Aß42 and Aß40 at a single interface in a wide detection range (10 fg/mL ∼ 1 µg/mL and 1 pg/mL ∼ 1 µg/mL) with detection limit of 4.5 fg/mL and 0.52 pg/mL, respectively. The proposed i-motif-based switchable sensing strategy paves a new avenue for a multiplex PEC assay on a single interface, showing great prospects in bioanalysis and early disease diagnosis.

Vitamin a supplementation during pregnancy in shaping child growth outcomes: A meta-analysis.

Abnormal fetal growth increases risks of childhood health complications. Vitamin A supplementation (VAS) is highly accessible, but literature inconsistency regarding effects of maternal VAS on fetal and childhood growth outcomes exists, deterring pregnant women from VAS during pregnancy. This meta-analysis aimed to analyze effects of vitamin A only or vitamin A + co-intervention during pregnancy in healthy mothers (MH) or with complications (MC, night blindness and HIV positive) on perinatal growth outcomes, also assess VAS dose impacts. The Cochrane Library, PubMed, ScienceDirect, Scopus, Embase and Web of Science databases were searched from inception to July 15, 2021. We covered subgroup analyses, including VAS in MH or MC within randomized controlled trial (RCT) or observational studies (OS). Fifty-five studies were included in this meta-analysis (426,098 pregnancies). Vitamin A decreased risk of preterm birth by 9% in MH-RCT (P < 0.001), by 62% in MH-OS (P = 0.029), by 10% in MC-RCT (P = 0.089); decreased LBW by 24% in MC-RCT (P = 0.032); increased neonatal weight in MC-RCT (SMD 0.96; P = 0.051). Besides, vitamin A + co-intervention decreased risks of preterm by 18% in MH-OS (P = 0.021); LBW by 25% in MH-OS (P < 0.001); by 32% in MC-RCT (P = 0.006); decreased neonatal defects by 33% in MH-OS (P = 0.064); decreased anemia by 25% in MH-OS (P = 0.0003); increased neonatal weight in MH-OS (SMD 0.51; P = 0.014); and increased neonatal length in MH-OS (SMD 1.83; P = 0.013). Meta-regression of VAS dose with individual outcomes was not significant, and no side effects were observed for VAS doses up to 4000 mcg (RAE/d). Regardless of maternal health conditions, VAS during pregnancy can safely and effectively improve fetal development and neonatal health even in mothers without VAD.

Clinical evaluation of deep learning-based clinical target volume three-channel auto-segmentation algorithm for adaptive radiotherapy in cervical cancer.

OBJECTIVES: Accurate contouring of the clinical target volume (CTV) is a key element of radiotherapy in cervical cancer. We validated a novel deep learning (DL)-based auto-segmentation algorithm for CTVs in cervical cancer called the three-channel adaptive auto-segmentation network (TCAS). METHODS: A total of 107 cases were collected and contoured by senior radiation oncologists (ROs). Each case consisted of the following: (1) contrast-enhanced CT scan for positioning, (2) the related CTV, (3) multiple plain CT scans during treatment and (4) the related CTV. After registration between (1) and (3) for the same patient, the aligned image and CTV were generated. Method 1 is rigid registration, method 2 is deformable registration, and the aligned CTV is seen as the result. Method 3 is rigid registration and TCAS, method 4 is deformable registration and TCAS, and the result is generated by a DL-based method. RESULTS: From the 107 cases, 15 pairs were selected as the test set. The dice similarity coefficient (DSC) of method 1 was 0.8155 ± 0.0368; the DSC of method 2 was 0.8277 ± 0.0315; the DSCs of method 3 and 4 were 0.8914 ± 0.0294 and 0.8921 ± 0.0231, respectively. The mean surface distance and Hausdorff distance of methods 3 and 4 were markedly better than those of method 1 and 2. CONCLUSIONS: The TCAS achieved comparable accuracy to the manual delineation performed by senior ROs and was significantly better than direct registration.

Sleep disturbance is associated with mild cognitive impairment: a community population-based cross-sectional study.

BACKGROUND: Sleep is conducive to the elimination of brain metabolites and the recovery of brain function. However, the relationship between sleep disturbance and Mild Cognitive Impairment is not fully been determined. METHODS: This was a community population-based cross-sectional study. A total of 1,443 participants from a village in the suburbs of Xi'an, China were enrolled in 2017. Sleep quality was evaluated using the Pittsburgh sleep quality index (PSQI), and sleep disturbance was defined as a PSQI score > 5. Mini-Mental State Examination (MMSE) was used to assess cognitive function and Mild Cognitive Impairment(MCI) was defined as the MMSE score less than cutoff values and meets the diagnostic criteria. Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and MCI. RESULTS: Among 1,443 subjects, 69(4.78%) had MCI, and 830 (57.52%) had sleep disturbance. In bivariate analysis, MCI was associated with sleep disturbance (ρ = 0.094, P<0.001). In the binary logistic regression, MCI was positively associated with the sleep disturbance (OR = 2.027, 95%CI = 1.112-3.698, P = 0.021). In the internal constitution of PSQI, MCI was negatively associated with the habitual sleep efficiency (OR = 0.447, 95%CI = 0.299-0.669, P < 0.001). Compared with waking up before or at 7 am, waking up after 7 am (OR = 0.555, 95%CI = 0.309-0.995, P = 0.048), or 8 am (OR = 0.296, 95%CI = 0.097-0.902, P = 0.032) was probably more likely to have normal cognition. However, people who slept more than 8 h a day might be more likely to suffer from MCI (OR = 5.560, 95%CI = 1.419-21.789, P = 0.014). CONCLUSION: Sleep disturbance is associated with Mild Cognitive Impairment. However, the causal relationship between them is not clear. It needs to be further studied.