An association study of m6A methylation with major depressive disorder.

OBJECTIVE: To find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD). METHODS: Differential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated. RESULTS: Differential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed. CONCLUSION: Among all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.

Mobile iodides capture for highly photolysis- and reverse-bias-stable perovskite solar cells.

For halide perovskites that are susceptible to photolysis and ion migration, iodide-related defects, such as iodine (I2) and iodine vacancies, are inevitable. Even a small number of these defects can trigger self-accelerating chemical reactions, posing serious challenges to the durability of perovskite solar cells. Fortunately, before I2 can damage the perovskites under illumination, they generally diffuse over a long distance. Therefore, detrimental I2 can be captured by interfacial materials with strong iodide/polyiodide (Ix-) affinities, such as fullerenes and perfluorodecyl iodide. However, fullerenes in direct contact with perovskites fail to confine Ix- ions within the perovskite layer but cause detrimental iodine vacancies. Perfluorodecyl iodide, with its directional Ix- affinity through halogen bonding, can both capture and confine Ix-. Therefore, inverted perovskite solar cells with over 10 times improved ultraviolet irradiation and thermal-light stabilities (under 85 °C and 1 sun illumination), and 1,000 times improved reverse-bias stability (under ISOS-V ageing tests) have been developed.

Iodide manipulation using zinc additives for efficient perovskite solar minimodules.

Interstitial iodides are the most critical type of defects in perovskite solar cells that limits efficiency and stability. They can be generated during solution, film, and device processing, further accelerating degradation. Herein, we find that introducing a small amount of a zinc salt- zinc trifluoromethane sulfonate (Zn(OOSCF3)2) in the perovskite solution can control the iodide defects in resultant perovskites ink and films. CF3SOO̶ vigorously suppresses molecular iodine formation in the perovskites by reducing it to iodide. At the same time, zinc cations can precipitate excess iodide by forming a Zn-Amine complex so that the iodide interstitials in the resultant perovskite films can be suppressed. The perovskite films using these additives show improved photoluminescence quantum efficiency and reduce deep trap density, despite zinc cations reducing the perovskite grain size and iodide interstitials. The zinc additives facilitate the formation of more uniform perovskite films on large-area substrates (78-108 cm2) in the blade-coating process. Fabricated minimodules show power conversion efficiencies of 19.60% and 19.21% with aperture areas of 84 and 108 cm2, respectively, as certified by National Renewable Energy Laboratory (NREL), the highest efficiency certified for minimodules of these sizes.

Unraveling radiation damage and healing mechanisms in halide perovskites using energy-tuned dual irradiation dosing.

Perovskite photovoltaics have been shown to recover, or heal, after radiation damage. Here, we deconvolve the effects of radiation based on different energy loss mechanisms from incident protons which induce defects or can promote efficiency recovery. We design a dual dose experiment first exposing devices to low-energy protons efficient in creating atomic displacements. Devices are then irradiated with high-energy protons that interact differently. Correlated with modeling, high-energy protons (with increased ionizing energy loss component) effectively anneal the initial radiation damage, and recover the device efficiency, thus directly detailing the different interactions of irradiation. We relate these differences to the energy loss (ionization or non-ionization) using simulation. Dual dose experiments provide insight into understanding the radiation response of perovskite solar cells and highlight that radiation-matter interactions in soft lattice materials are distinct from conventional semiconductors. These results present electronic ionization as a unique handle to remedying defects and trap states in perovskites.

Toward the Commercialization of Perovskite Solar Modules.

Perovskite (PVSK) photovoltaic (PV) devices are undergoing rapid development and have reached a certified power conversion efficiency (PCE) of 26.1% at the cell level. Tremendous efforts in material and device engineering have also increased moisture, heat, and light-related stability. Moreover, the solution-process nature makes the fabrication process of perovskite photovoltaic devices feasible and compatible with some mature high-volume manufacturing techniques. All these features render perovskite solar modules (PSMs) suitable for terawatt-scale energy production with a low levelized cost of electricity (LCOE). In this review, the current status of perovskite solar cells (PSCs) and modules and their potential applications are first introduced. Then critical challenges are identified in their commercialization and propose the corresponding solutions, including developing strategies to realize high-quality films over a large area to further improve power conversion efficiency and stability to meet the commercial demands. Finally, some potential development directions and issues requiring attention in the future, mainly focusing on further dealing with toxicity and recycling of the whole device, and the attainment of highly efficient perovskite-based tandem modules, which can reduce the environmental impact and accelerate the LCOE reduction are put forwarded.

How spin relaxes and dephases in bulk halide perovskites.

Spintronics in halide perovskites has drawn significant attention in recent years, due to their highly tunable spin-orbit fields and intriguing interplay with lattice symmetry. Here, we perform first-principles calculations to determine the spin relaxation time (T1) and ensemble spin dephasing time ([Formula: see text]) in a prototype halide perovskite, CsPbBr3. To accurately capture spin dephasing in external magnetic fields we determine the Landé g-factor from first principles and take it into account in our calculations. These allow us to predict intrinsic spin lifetimes as an upper bound for experiments, identify the dominant spin relaxation pathways, and evaluate the dependence on temperature, external fields, carrier density, and impurities. We find that the Fröhlich interaction that dominates carrier relaxation contributes negligibly to spin relaxation, consistent with the spin-conserving nature of this interaction. Our theoretical approach may lead to new strategies to optimize spin and carrier transport properties.

Light-enhanced oxygen degradation of MAPbBr3 single crystal.

Organometal halide perovskites are promising materials for optoelectronic applications, whose commercial realization depends critically on their stability under multiple environmental factors. In this study, a methylammonium lead bromide (MAPbBr3) single crystal was cleaved and exposed to simultaneous oxygen and light illumination under ultrahigh vacuum (UHV). The exposure process was monitored using X-ray photoelectron spectroscopy (XPS) with precise control of the exposure time and oxygen pressure. It was found that the combination of oxygen and light accelerated the degradation of MAPbBr3, which could not be viewed as a simple addition of that by oxygen-only and light-only exposures. The XPS spectra showed significant loss of carbon, bromine, and nitrogen at an oxygen exposure of 1010 Langmuir with light illumination, approximately 17 times of the additive effects of oxygen-only and light-only exposures. It was also found that the photoluminescence (PL) emission was much weakened by oxygen and light co-exposure, while previous reports had shown that PL was substantially enhanced by oxygen-only exposure. Measurements using a scanning electron microscope (SEM) and focused ion beam (FIB) demonstrated that the crystal surface was much roughened by the co-exposure. Density functional theory (DFT) calculations revealed the formation of superoxide and oxygen induced gap state, suggesting the creation of oxygen radicals by light illumination as a possible microscopic driving force for enhanced degradation.

Lithium Slag and Solid Waste-Based Binders for Cemented Lithium Mica Fine Tailings Backfill.

To mitigate the adverse effects of fine-grained lithium mica tailings and other solid wastes generated from the extraction of lithium ore mining, as well as the limitations of traditional cement-based binders for lithium mica fine tailings, this study explores the feasibility of using a binder composed of ordinary Portland cement, lithium slag, fly ash, and desulfurization gypsum to stabilize lithium fine tailings into cemented lithium tailings backfill. Compared with traditional cementitious binders, an extensive array of experiments and analyses were conducted on binders formed by various material proportion combinations, employing uniaxial compressive strength tests, microstructural morphology, grayscale analyses, and flowability tests. The results show the following: (1) In this study, an LSB binder exhibiting superior mechanical properties compared to traditional cementitious binders was identified, with an optimal OPC:LS:FA:DG ratio of 2:1:1:1. (2) In the context of cemented lithium mica fine tailings, the LSB-CLTB material exhibits higher unconfined compressive strength and lower self-weight compared to OPC-CLTB materials. At a binder content of 10 wt%, the UCS values achieved by the LSB-CLTB material at curing periods of 7 days, 14 days, and 28 days are 0.97 MPa, 1.52 MPa, and 2.1 MPa, respectively, representing increases of 40.6%, 34.5%, and 44.8% over the compressive strength of OPC-based materials under the same conditions. (3) The LSB binder not only exhibits enhanced pozzolanic reactivity but also facilitates the infilling of detrimental pores through its inherent particle size and the formation of AFt and C-(A)-S-H gels via hydration reactions, thereby effectively improving the compressive strength performance of fine-grained tailings backfill.

Evaluation of the liver targeting and anti­liver cancer activity of artesunate­loaded and glycyrrhetinic acid­coated nanoparticles.

Globally, liver cancer ranks among the most lethal cancers, with chemotherapy being one of its primary treatments. However, poor selectivity, systemic toxicity, a narrow treatment window, low response rate and multidrug resistance limit its clinical application. Liver-targeted nanoparticles (NPs) exhibit excellent targeted delivery ability and promising effectivity in treating liver cancer. The present study aimed to investigate the liver-targeting and anti-liver cancer effect of artesunate (ART)-loaded and glycyrrhetinic acid (GA)-decorated polyethylene glycol (PEG)-poly (lactic-co-glycolic acid) (PLGA) (ART/GA-PEG-PLGA) NPs. GA-coated NPs significantly increased hepatoma-targeted cellular uptake, with micropinocytosis and caveolae-mediated endocytosis as its chief internalization pathways. Moreover, ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells, mainly via the induction of a high level of reactive oxygen species, decline in mitochondrial membrane potential and induction of cell cycle arrest. Additionally, ART/GA-PEG-PLGA NPs induced internal apoptosis pathways by upregulating the activity of cleaved caspase-3/7 and expression of cleaved poly (ADP-Ribose)-polymerase and Phos-p38 mitogen-activated protein kinase in HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Finally, ART/GA-PEG-PLGA NPs promoted the liver-targeting distribution of ART, increased the retention time and promoted its antitumour effects in vivo. Therefore, ART/GA-PEG-PLGA NPs afforded excellent hepatoma-targeted delivery and anti-liver cancer efficacy, and thus, they may be a promising strategy for treating liver cancer.

CuPc Passivation of a MAPbBr3 Single Crystal Surface.

In this study, a facile passivation for methylammonium lead bromide (MAPbBr3) single crystals is reported. Stability against moisture and light remains the most critical demerit of perovskite materials, which is improved by depositing a 40 Å thick hydrophobic copper phthalocyanine (CuPc) layer on top of the cleaved perovskite surface. The water and light exposure processes were monitored with X-ray photoelectron spectroscopy with precise control of the exposure time and pressure. It is found that the CuPc top layer could protect the sample from moisture infiltration at a water exposure of 1013 L, while the nonpassivated sample started to degrade at 108 L. During the light exposure, CuPc also slowed down the light-induced degradation, which is supported by the elemental ratio change of metallic lead and bromine. These results are further confirmed by the morphological comparison via scanning electron microscopy and focused ion beam.

An association study of clock genes with major depressive disorder.

OBJECTIVE: To study the relationship between clock genes and Major Depressive Disorder (MDD). METHODS: GEO database was used to obtain the chip data and clinical information of datasets GSE98793, GSE39653 and GSE52790. The differentially expressed clock genes were found through the analysis of the differentially expressed genes between MDD and healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) enrichment analysis were performed on the differential expressed clock genes. Lasso Regression and Support Vector Machine (SVM) method were used for screening the differential expressed clock genes. Logistic regression was used to establish a diagnostic model for depression with the screened genes. Receiver Operating Characteristic (ROC) Curve was used to verify the model. Gene differential expression analysis was performed for MDD with high scores and MDD with low scores in the diagnostic model. Gene Set Enrichment Analysis (GSEA) enrichment analysis was performed for differentially expressed genes. Single-gene GSEA was used to analyze each gene in the model separately. Cibersort method was used to analyze the immune infiltration of MDD and healthy controls, and the correlation between immune cells and clock genes was analyzed. Cytoscape was used to analyze the clock gene interaction network. The DGIdb website was used to predict potentially effective therapeutic drugs for clock genes closely related to MDD. RESULTS: Six genes were identified by differential expression analysis of clock genes between MDD and healthy controls. GO and KEGG enrichment analysis of 6 genes showed that their pathways were concentrated such as circadian rhythm, rhythmic process, TGF - beta signaling pathway, longevity regulating pathway-multiple species, adipocytokine signaling pathway and so on. Lasso regression and SVM were used to screen out 5 clock genes (HDAC1, ID3, NFIL3, PRKAA1, TNF) for MDD. The diagnostic model of depression was established according to the 5 clock genes. The area under the curve (AUC) of the established depression diagnostic model was 0.686. Gene difference analysis was performed between MDD patients with high score of clock gene diagnostic model and MDD patients with low score. GSEA was performed for the differential genes showed that the most enriched pathways were:adipocytokine signaling pathway, TGF beta signaling pathway, oxidative phosphorylation, primary immunodeficiency, and so on. The single gene GSEA showed that the most enriched pathways were Toll like receptor signaling pathway, glucolipid metabolism, amino acid metabolism, neuroactive ligand receptor interaction, and so on. The results of immune infiltration analysis showed that NK cells resting and Macrophages M2 were different between MDD and control groups. In MDD, the gene closely related to NK cells resting was HDAC1, and the genes closely related to Macrophages M2 were HDAC1 and NFIL3. The RNA interactions network of clock genes shows that the regulation process is complex, which can provide a reference for subsequent related research. Potential therapeutic drugs predict display, among the 5 clock genes, TNF, HDAC1, and PRKAA1 may have potential effective therapeutic drugs. CONCLUSION: Among all CLOCK genes, HDAC1, ID3, NFIL3, PRKAA1, TNF are closely related to MDD. Among them, TNF, HDAC1, and PRKAA1 may have potential effective therapeutic drugs.

A long trend of sexually transmitted diseases before and after the COVID-19 pandemic in China (2010-21).

BACKGROUND: The longer ongoing benefits of coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPIs) for sexually transmitted diseases (STDs) in China are still unclear. We aimed to explore the changes in five STDs (AIDS, hepatitis B, hepatitis C, gonorrhoea, and syphilis) before, during, and after the COVID-19 pandemic in mainland China, from 2010 to 2021. METHODS: The number of the monthly reported cases of the five STDs were extracted from the website to construct the Joinpoint regression and autoregressive integrated moving average (ARIMA) models. Eight indicators reflecting NPIs were chosen from the COVID-19 Government Response Tracker system. The STDs and eight indicators were used to establish the Multivariable generalised linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: With the exception of hepatitis B, the other four STDs (AIDS, hepatitis C, gonorrhoea, and syphilis) had a positive average annual percent change over the past 12years. All the ARIMA models had passed the Ljung-Box test, and the predicted data fit well with the data from 2010 to 2019. All five STDs were significantly reduced in 2020 compared with 2019, with significant estimated IRRs ranging from 0.88 to 0.92. In the GLM, using data for the years 2020 (February-December) and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated that the incidence of the five STDs decreased rapidly during the COVID-19 pandemic in 2020. A recovery of STDs in 2021 was found to occur compared with that in 2020, but the rising trend disappeared after adjusting for the NPIs. Our study demonstrated that NPIs have an effect on STDs, but the relaxation of NPI usage might lead to a resurgence.

Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents.

Objective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents. Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed. Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 µM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice. Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.

pH-Responsive and liver-targeting drug delivery system for combination delivery of artesunate with arsenic trioxide prodrug against hepatocellular carcinoma.

OBJECTIVE: Arsenic trioxide (ATO) exerts therapeutic effects on various solid tumors, and artesunate (ART) synergizes with antitumor drugs. We herein combined ART and an ATO prodrug (ATOP) in pH-responsive and liver-targeting liposomes to improve targeted hepatocellular carcinoma (HCC) treatment. METHODS: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-hydrazone (HYD)-polyethylene glycol (PEG)-glycyrrhetinic acid (GA) (DSPE-HYD-PEG-GA) was synthesized and characterized. The optimal ratio of ART and ATOP was selected. Calcium arsenate nanoparticles (CaAs NPs) and DSPE-HYD-PEG-GA@ART/CaAs NPs liposomes were prepared and their physicochemical properties were characterized. Their intracellular uptake, intracellular localization, uptake pathway identification, cytotoxicity, proapoptotic effects, and relevant mechanisms were studied. RESULTS: The DSPE-HYD-PEG-GA was successfully synthesized. The best ratio of ART and ATOP was 7:1. The particle size of CaAs NPs under transmission electron microscopy was 142.39 ± 21.50 nm. Arsenic (As), calcium, and oxygen elements were uniformly distributed in CaAs NPs, and the drug loading and encapsulation efficiency of As are 37.28% and 51.40%, respectively. The liposomes were elliptical, and the particle size was 100.91 ± 39.31 nm. The liposome cell intake was significantly increased in Huh-7 cells. The liposomes entered the cell through macropinocytosis and caveolin-mediated endocytosis and were predominantly distributed in the cytoplasm. They exerted an excellent inhibitory effect on Huh-7 cells and promoted tumor cell apoptosis through lipid peroxidation, mitochondrial membrane potential reduction, and cell-cycle blockage. CONCLUSIONS: The pH-responsive and liver-targeting drug delivery system for the combination delivery of ART with ATOP showed promising effects on hepatocellular carcinoma (HCC).

A novel framework to predict chlorophyll-a concentrations in water bodies through multi-source big data and machine learning algorithms.

Eutrophication happens when water bodies are enriched by minerals and nutrients. Dense blooms of noxious are the most obvious effect of eutrophication that harms water quality, and by increasing toxic substances damage the water ecosystem. Therefore, it is critical to monitor and investigate the development process of eutrophication. The concentration of chlorophyll-a (chl-a) in water bodies is an essential indicator of eutrophication in them. Previous studies in predicting chlorophyll-a concentrations suffered from low spatial resolution and discrepancies between predicted and observed values. In this paper, we used various remote sensing and ground observation data and proposed a novel machine learning-based framework, a random forest inversion model, to provide the spatial distribution of chl-a in 2 m spatial resolution. The results showed our model outperformed other base models, and the goodness of fit improved by over 36.6% while MSE and MAE decreased by over 15.17% and over 21.26% respectively. Moreover, we compared the feasibility of GF-1 and Sentinel-2 remote sensing data in chl-a concentration prediction. We found that better prediction results can be obtained by using GF-1 data, with the goodness of fit reaching 93.1% and MSE only 3.589. The proposed method and findings of this study can be used in future water management studies and as an aid for decision-makers in this field.

Single-cell RNA-seq uncovers distinct pathways and genes in endothelial cells during atherosclerosis progression.

Background: Atherosclerosis (AS) is a chronic inflammatory disease involving various cell types, cytokines, and adhesion molecules. Herein, we aimed to uncover its key molecular mechanisms by single-cell RNA-seq (scRNA-seq) analysis. Methods: ScRNA-seq data of cells from atherosclerotic human coronary arteries were analyzed using the Seurat package. Cell types were clustered, and differentially expressed genes (DEGs) were screened. GSVA (Gene Set Variation Analysis) scores of hub pathways were compared among different cell clusters. DEGs in endothelial cells between apolipoprotein-E (ApoE)-/- mice and specific TGFbR1/2 KO ApoE-/- mice fed with high-fat diet were overlapped with those from human AS coronary arteries. In fluid shear stress and AS, hub genes were determined based on the protein-protein interaction (PPI) network, which were verified in ApoE-/- mice. Finally, hub genes were validated in three pairs of AS coronary arteries and normal tissues by histopathological examination. Results: ScRNA-seq identified nine cell clusters in human coronary arteries, namely, fibroblasts, endothelial cells, macrophages, B cells, adipocytes, HSCs, NK cells, CD8+ T cells, and monocytes. Among them, endothelial cells had the lowest fluid shear stress and AS and TGF-beta signaling pathway scores. Compared to ApoE-/- mice fed with normal diet, fluid shear stress and AS and TGF-beta scores were both significantly lower in endothelial cells from TGFbR1/2 KO ApoE-/- mice fed with normal or high-fat diet. Furthermore, the two hub pathways had a positive correlation. Three hub genes (ICAM1, KLF2, and VCAM1) were identified, and their expression was distinctly downregulated in endothelial cells from TGFbR1/2 KO ApoE-/- mice fed with normal or high-fat diet than in those from ApoE-/- mice fed with a normal diet, which were confirmed in human AS coronary artery. Conclusion: Our findings clarified the pivotal impacts of pathways (fluid shear stress and AS and TGF-beta) and genes (ICAM1, KLF2, and VCAM1) in endothelial cells on AS progression.

Lead-chelating hole-transport layers for efficient and stable perovskite minimodules.

The defective bottom interfaces of perovskites and hole-transport layers (HTLs) limit the performance of p-i-n structure perovskite solar cells. We report that the addition of lead chelation molecules into HTLs can strongly interact with lead(II) ion (Pb2+), resulting in a reduced amorphous region in perovskites near HTLs and a passivated perovskite bottom surface. The minimodule with an aperture area of 26.9 square centimeters has a power conversion efficiency (PCE) of 21.8% (stabilized at 21.1%) that is certified by the National Renewable Energy Laboratory (NREL), which corresponds to a minimal small-cell efficiency of 24.6% (stabilized 24.1%) throughout the module area. Small-area cells and large-area minimodules with lead chelation molecules in HTLs had a light soaking stability of 3010 and 2130 hours, respectively, at an efficiency loss of 10% from the initial value under 1-sun illumination and open-circuit voltage conditions.

A Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD): study protocol for a randomized clinical trial and prognosis study.

BACKGROUND: Major depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, closely associated with bipolar disorder (BD). However, there is still a lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about how to identify AFD, what is the appropriate individualized treatment for AFD, and what are the predictive biomarkers of conversion to BD. METHODS: The Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective, open-label study consisting of a 12-week randomized controlled trial (RCT) and a continued follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. Firstly, multivariate informatics analyses are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD, and patients with HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including "single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)", "SSRI/SNRI combined with mood stabilizer," "SSRI/SNRI combined with quetiapine (≥ 150 mg/day)," or "treatment as usual (TAU)" and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up until 4 years or switching to BD, to explore the risk factors of conversion from atypical depression to BD and eventually build the risk warning model of conversion to BD. DISCUSSION: The first enrolment was in August 2019. The iDoT-AFD study explores the clinical and biological markers for the diagnosis, treatment, and prognosis of AFD and further provides evidence for clinical guidelines of AFD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04209166. Registered on December 19, 2019.

SARS-CoV-2 omicron BA.1.1 is highly resistant to antibody neutralization of convalescent serum from the origin strain.

The emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.1.1) has attracted global attention. The numerous mutations in the spike protein suggest that it may have altered susceptibility to immune protection elicited by the existing coronavirus disease 2019 (COVID-19) infection. We used a live virus neutralization test and SARS-CoV-2 pseudotype vesicular stomatitis virus vector-based neutralization assay to assess the degree of immune escape efficiency of the original, Delta (B1.617.2), and Omicron strains against the serum antibodies from 64 unvaccinated patients who had recovered from COVID-19 and the results were strongly correlated. The convalescent serum neutralization was more markedly reduced against the Omicron variant (9.4-57.9-fold) than the Delta variant (2.0-4.5-fold) as compared with the original strain. Our results demonstrate the reduced fusion and notable immune evasion capabilities of the Omicron variants, highlighting the importance of accelerating the development of vaccines targeting them.