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Both feline coronavirus (FCoV) and SARS-CoV-2 are coronaviruses that infect cats and humans, respectively. However, cats have been shown to be susceptible to SARS-CoV-2, and FCoV also had been shown to infect human. To elucidate the relationship between FCoV and SARS-CoV-2, we highlight the main characteristics of the genome, the receptor usage, and the correlation of the receptor-binding domain (RBD) of spike proteins in FCoV and SARS-CoV-2. It is demonstrated that FCoV and SARS-CoV-2 are closely related to the main characteristics of the genome, receptor usage, and RBD of spike proteins with similar furin cleavage sites. In particular, the affinity of the conserved feline angiotensin-converting enzyme 2 (fACE2) receptor to the RBD of SARS-CoV-2 suggests that cats are susceptible to SARS-CoV-2. In addition, cross-species of coronaviruses between cats and humans or other domesticated animals are also discussed. This review sheds light on cats as potential intermediate hosts for SARS-CoV-2 transmission, and cross-species transmission or zoonotic infection of FCoV and SARS-CoV-2 between cats and humans was identified.

Description, Greater representational transformation during encoding is associated with stronger semantic formats and better long-term memory., Memory is often conceived as a dynamic process that involves substantial transformations of mental representations. However, the neural mechanisms underlying these transformations and their role in memory formation and retrieval have only started to be elucidated. Combining intracranial EEG recordings with deep neural network models, we provide a detailed picture of the representational transformations from encoding to short-term memory maintenance and long-term memory retrieval that underlie successful episodic memory. We observed substantial representational transformations during encoding. Critically, more pronounced semantic representational formats predicted better subsequent long-term memory, and this effect was mediated by more consistent item-specific representations across encoding events. The representations were further transformed right after stimulus offset, and the representations during long-term memory retrieval were more similar to those during short-term maintenance than during encoding. Our results suggest that memory representations pass through multiple stages of transformations to achieve successful long-term memory formation and recall.

In this paper, the effect of Rh content on the mechanical properties of Ir–Rh alloys was investigated based on first-principles density functional theory. The calculated results show that when the Rh content is small, the three elastic moduli (elastic modulus (B), shear modulus (G), and Young’s modulus (E)) of Ir–Rh alloy increase rapidly with the increase of Rh content. They reach a maximum value at Ir–10Rh and then decrease, before rising slowly at Ir–40Rh and then gradually decreasing again. This shows that adding a small amount of rhodium to iridium can effectively improve the strength and hardness of iridium. Among all the components of the selected Ir–Rh alloys, Ir–10Rh has the highest hardness and strength. The addition of Rh can cause the embrittlement of Ir–Rh alloys, and its brittleness first increases and then decreases with the increase of Rh content, and reaches the highest at Ir–50Rh. Considering the results obtained from theoretical calculations and experiments, Ir–20Rh was selected as the alloy composition for the study of hot isostatic pressing technology. The effects of mixing time, whether to mix powder with balls, and degassing temperature on the properties of metal powders were studied to find the best mixing and degassing process parameters. In the experiment of mixing powder for the iridium and rhodium alloy, it is found that the time required for mixing powder with balls to reach uniformity was shorter than that without balls. The oxygen content of the final mixed powder obtained by the two processes is the same. The nitrogen content of the metal powder mixed with the ball is slightly higher than that without the ball, but it can be reduced to below 0.001% after the degassing process. During the sintering process, with the increase in temperature, the mutual diffusion speed between iridium powder and rhodium powder increases, the sintering neck grows, the internal pores decrease, and the density of the sintered body increases. Therefore, the final decision process is to select mixing with balls for 10 h, degas at 1200 °C for 2 h, and then raise the temperature to 1800 °C for sintering. With the increase of hot isostatic pressing temperature and pressure, the density of the alloy increases. When the highest temperature (1300 °C) and highest pressure (140 MPa) are used for hot isostatic pressing for 2 h, the density can reach 95.7% of the theoretical density.

Background: Almost all patients with lung adenocarcinoma (LUAD) develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs. Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, LDH, flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, the apoptosis rate, and stemness. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and Western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cyclohexane, MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B. Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and stemness were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib . When LUAD cells were treated with the ubiquitin-specific inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro . Conclusions: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.

Brain signal variability has been consistently linked to functional integration; however, whether this coupling is associated with cognitive functions and/or psychiatric diseases has not been clarified. Using multiple multimodality datasets, including resting-state functional magnetic resonance imaging (rsfMRI) data from the Human Connectome Project (HCP: N = 927) and a Beijing sample (N = 416) and cerebral blood flow (CBF) and rsfMRI data from a Hangzhou sample (N = 29), we found that, compared with the existing variability measure (i.e., SDBOLD), the mean-scaled (standardized) fractional standard deviation of the BOLD signal (mfSDBOLD) maintained very high test-retest reliability, showed greater cross-site reliability and was less affected by head motion. We also found strong reproducible couplings between the mfSDBOLD and functional integration measured by the degree centrality (DC), both cross-voxel and cross-subject, which were robust to scanning and preprocessing parameters. Moreover, both mfSDBOLD and DC were correlated with CBF, suggesting a common physiological basis for both measures. Critically, the degree of coupling between mfSDBOLD and long-range DC was positively correlated with individuals’ cognitive total composite scores. Brain regions with greater mismatches between mfSDBOLD and long-range DC were more vulnerable to brain diseases. Our results suggest that BOLD signal variability could serve as a meaningful index of local function that underlies functional integration in the human brain and that a strong coupling between BOLD signal variability and functional integration may serve as a hallmark of balanced brain networks that are associated with optimal brain functions.

Epidemiological investigations have shown that patients with Parkinson’s disease (PD) have a lower probability of developing lung cancer. Subsequent research revealed that PD and lung cancer share specific genetic alterations. Therefore, the utilisation of PD biomarkers and therapeutic targets may improve lung adenocarcinoma (LUAD) diagnosis and treatment. We aimed to identify a gene-based signature from 25 Parkinson family genes for LUAD prognosis and treatment choice. We analysed Parkinson family gene expression and protein levels in LUAD, utilising multiple databases. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a prognostic model based on the TCGA-LUAD cohort. We validated the model in external GEO cohorts. Immune cell infiltration was compared between risk groups, and GEO data was used to explore the model’s predictive ability for LUAD treatment response. Nearly all Parkinson family genes exhibited significant differential expression between LUAD and normal tissues. LASSO regression confirmed that our seven Parkinson family gene-based signature had excellent prognostic performance for LUAD, as validated in three GEO cohorts. The high-risk group was clearly associated with low tumour immune cell infiltration, suggesting that immunotherapy may not be an optimal treatment choice. This is the first Parkinson family gene-based model for the prediction of LUAD prognosis and treatment outcome. The association of these genes with poor prognosis and low immune infiltration requires further investigation.

Aberrant expression of microRNAs (miRNAs/miRs) is associated with the initiation and progression of colorectal cancer (CRC), but how they regulate colorectal tumorigenesis is still unknown. The present study was designed to investigate the expression profile of miRNAs in human CRC tissues, and to reveal the molecular mechanism of miRNA-142-3p in suppressing colon cancer cell proliferation. The expression of miRNA was examined using an Exiqon miRNA array. Bioinformatics was used to predict the target genes of differentially expressed miRNAs and to analyze their biological function in CRC. The effect of miR-142-3p in colon cancer cells was evaluated in vitro using cell proliferation, colony formation and Transwell assays. Dual-luciferase reporter gene assays were performed to investigate the association between miR-142-3p and Rac family small GTPase 1 (RAC1). The effect of miR-142-3p regulation on colon cancer proliferation was assessed through western blotting and quantitative polymerase chain reaction analysis. Compared with their expression in adjacent non-cancer mucosal tissues, 76 miRNAs were upregulated and 102 miRNAs were downregulated in CRC. One of the most significantly and differentially regulated miRNAs was miR-142-3p, which was downregulated in 81.0% (51/63) of primary CRC tissues. After transfection of miR-142-3p mimics into colon cancer cells, proliferation and colony formation were decreased, and migration and invasion were markedly suppressed. RAC1 was a possible target of miR-142-3p, which was confirmed by dual-luciferase reporter assay. Transfection of miR-142-3p mimics decreased the levels of RAC1 and suppressed epithelial-to-mesenchymal transition in colon cancer cells. The phosphorylation of extraceullar signal-regulated kinase (ERK) was decreased significantly by the inhibition of RAC1 or transfection of miR-142-3p mimics in colon cancer cells. In conclusion, aberrant miRNAs are implicated in CRC. Decreased expression of miR-142-3p may be associated with CRC tumorigenesis via Rac1-ERK signaling.

We propose a ridge-penalized adaptive Mantel test (AdaMant) for evaluating the association of two high-dimensional sets of features. By introducing a ridge penalty, AdaMant tests the association across many metrics simultaneously. We demonstrate how ridge penalization bridges Euclidean and Mahalanobis distances and their corresponding linear models from the perspective of association measurement and testing. This result is not only theoretically interesting but also has important implications in penalized hypothesis testing, especially in high-dimensional settings such as imaging genetics. Applying the proposed method to an imaging genetic study of visual working memory in healthy adults, we identified interesting associations of brain connectivity (measured by electroencephalogram coherence) with selected genetic features.

Objectives: Chronic heart failure (CHF) is a chronic and progressive disease with high incidence. The aim of this study was to evaluate the effectiveness and safety of Xinmailong injection...

Equilibrium swelling test was employed to determine the swelling responses of Fluororubber (FKM) and Fluorosilicone Rubber (FVMQ) in different types of solvents, and the one-dimensional solubility parameters of FKM and FVMQ were obtained with a range of 17–25 MPa1/2 and 16–20 MPa1/2 respectively. It was attempted to calculate the three-dimensional solubility parameters (HSP) of FKM and FVMQ by using a professional computer software, and a new type of bio-fuel, represented by biodiesel, was further selected as an object in this work to investigate its swellability. Flory-Huggins interaction parameter (χHSP) between FKM, FVMQ and each solvents used in this work was calculated by HSP values, and the results turned out that the swelling ratio (q) decreased with increasing χHSP value. By mathematical fitting, two functional relationships between q and χHSP for FKM and FVMQ were achieved to predict the swelling properties of rubber in fluids. The increasing use of biodiesel with their effect on rubber materials has become an important topic of industrial research. The second components, including ethanol and ethylene glycol, were added into biodiesel with the purpose of cost reduction, which however might cause a critical increase of rubber swelling. One of the possible applications of χHSP values is the prediction or explanation of swelling behavior. Therein, χHSP values between FKM, FVMQ and biodiesel/additive blends were calculated and found that χHSP firstly decreased and then increased with increase of the additive (ethanol and ethylene glycol) content. Taking advantage of this tendency one can predict the swelling properties of rubber products in the biodiesel blends and provide an important reference for such applications in liquid medium.

Six new monoterpenoid glycosides, including thymoquinol 5-O-α-L-arabinopyranosyl-(1 → 6)-β-D-glucopyranoside (1), cuminic acid 7-O-α-D-arabinofuranosyl-(1 → 6)-β- d -glucopyranosyl ester (2), p-cymene 7-O-α-D-arabinofuranosyl-(1 → 6)-β-D-glucopyranoside (3), p-methylhyd- ratropic acid 9-O-α-D-arabinofuranosyl-(1 → 6)-β- d -glucopyranosyl ester (4), (R)-p-cymene 9-O-α- D-arabinofuranosyl-(1 → 6)-β-D-glucopyranoside (5), and (R)-p-cymene 9-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (6), together with three known compounds, such as (R)-p-cymene 9-O-β-D-glucopyranoside (7), thymoquinol 5-O-β-D-glucopyranoside (8), and thymoquinol 2-O-β-D-glucopyranoside (9) were isolated from the 70%-EtOH extract of Schisandra chinensis rattan stems. The structures of the new compounds were elucidated by detailed spectroscopic analyses. Meanwhile, the neuroprotective activities of compounds 1–9 were evaluated on the two co-culture models of microglia and neurons cells and astrocytoma and neurons cells

By means of the electrochemical workstation, scanning electron microscope, energy spectrometer and so on, the polarization curves and galvanic corrosion parameters of the front surface (FS) specimen and side surface (SS) specimen of CF8611/AC531 composite and the 7B04-T74 aluminum alloy in the electrolyte of 3.5% (mass fraction, the same below) NaCl or 3.5%NaCl+12.5% Cu2SO4 were measured, meanwhile the microstructure were observed. Based on the electrochemistry theory, steady corrosion field and parametric scanning technology, a dynamic model for galvanic corrosion under the wear status of composite was established. The results show that the performance of this composite is stable, but there are some carbon fibre exposed defects on the original surface. The defects are often located at the overlap area of carbon fibre bundles. There are 4.3 defects per square millimetre and the average area of each defect is 0.0184mm2; the cathodic reaction rate is closely related to the area of the defects and consequently its surface is divided into the active and the inert cathode region; in the galvanic corrosion the main corrosion form of the aluminum alloy is pitting and no failure is found in the composite. The galvanic corrosion model established here is valid and available. There is a positive linear correlation between the total galvanic current Ig and the defect area S; the galvanic effect of FS and SS on the aluminum alloy is the same when SFS:SSS is about 5.53:1.

Mutual influences between anxiety and working memory (WM) have been extensively studied, and their curvilinear relationship resembles the classic Yerkes-Dodson law of arousal and performance. Given the genetic bases of both anxiety and WM, it is likely that the individual differences in the Yerkes-Dodson law of anxiety and WM may have genetic correlates. The current genome wide association study (GWAS) enrolled 1115 healthy subjects to search for genes that are potential moderators of the association between anxiety and WM. Results showed that CPNE3 rs10102229 had the strongest effect, p = 3.38E−6 at SNP level and p = 2.68E−06 at gene level. Anxiety and WM had a significant negative correlation (i.e., more anxious individuals performed worse on the WM tasks) for the TT genotype of rs10102229 (resulting in lower expression of CPNE3), whereas the correlation was positive (i.e., more anxious individuals performed better on the WM tasks) for the CC carriers. The same pattern of results was found at the gene level using gene score analysis. These effects were replicated in an independent sample (N = 330). The current study is the first to report a gene that moderates the relation between anxiety and WM and potentially provides a genetic explanation for the classic Yerkes-Dodson law.

Purpose Clinical evidence of metastasis with ground-glass nodules (GGNs) has been reported, including pulmonary metastasis and distant metastasis. However, the clonal relationships of multiple GGNs at the genetic level remain unclear. Experimental design Sixty tissue specimens were obtained from 19 patients with multiple GGN lung cancer who underwent surgery in 2019. Whole exome sequencing (WES) was performed on tissue samples, and genomic profiling and clone evolution analysis were conducted to investigate the genetic characteristics and clonality of multiple GGNs. Results A total of 15,435 nonsynonymous mutations were identified by WES, and GGNs with shared nonsynonymous mutations were observed in seven patients. Copy number variant (CNV) analysis showed that GGNs in ten patients had at least one shared arm-level CNV. Mutational spectrum analysis showed that GGNs in three patients had similar six substitution profiles and GGNs in fou patients had similar 96 substitution profiles. According to the clone evolution analysis, we found that GGNs in five patients had shared clonal driver gene mutations. Taken together, we identified that 5 patients may have multiple primary GGNs without any similar genetic features, 2 patients may have intrapulmonary metastatic GGNs with ≥ 3 similar genetic features, and the other 12 patients cannot be determined due to insufficient evidences in our cohort. Conclusions Our findings suggest that the intrapulmonary metastasis exist in multiple GGNs, but the number of GGNs was not associated with the probability of metastasis. Application of genomic profiling may prove to be important to precise management of patients with multiple GGNs.

Visual short-term memory (VSTM) enables humans to form a stable and coherent representation of the external world. However, the nature and temporal dynamics of the neural representations in VSTM that support this stability are barely understood. Here we combined human intracranial electroencephalography (iEEG) recordings with analyses using deep neural networks and semantic models to probe the representational format and temporal dynamics of information in VSTM. We found clear evidence that VSTM maintenance occurred in two distinct representational formats which originated from different encoding periods. The first format derived from an early encoding period (250 to 770 ms) corresponded to higher-order visual representations. The second format originated from a late encoding period (1,000 to 1,980 ms) and contained abstract semantic representations. These representational formats were overall stable during maintenance, with no consistent transformation across time. Nevertheless, maintenance of both representational formats showed substantial arrhythmic fluctuations, i.e., waxing and waning in irregular intervals. The increases of the maintained representational formats were specific to the phases of hippocampal low-frequency activity. Our results demonstrate that human VSTM simultaneously maintains representations at different levels of processing, from higher-order visual information to abstract semantic representations, which are stably maintained via coupling to hippocampal low-frequency activity.

The aging of the nervous system is a heterogeneous process. It remains a significant challenge to identify relevant markers of pathological and healthy brain aging. A central aspect of aging are decreased sensory acuities, especially because they correlate with the decline in higher cognitive functioning. Sensory and higher cognitive processing relies on information flow between distant brain areas. Aging leads to disintegration of the underlying white matter tracts. While this disintegration is assumed to contribute to higher cognitive decline, data linking structural integrity and sensory function are sparse. The investigation of their interrelation may provide valuable insight into the mechanisms of brain aging. We used a combined behavioral and neuroimaging approach and investigated to what extent changes in microstructural white matter integrity reflect performance declines in tactile pattern recognition with aging. Poor performance in older participants was related to decreased integrity in the anterior corpus callosum. Probabilistic tractography showed that this structure is connected to the prefrontal cortices. Our data point to decreased integrity in the anterior corpus callosum as a marker for advanced brain aging. The correlation between impaired tactile recognition and disintegration in frontal brain networks could provide an explanation why the decrease of sensory function predicts cognitive decline.

In this study, the effects of Goose parvovirus (GPV) infection as well as the possible role of NS1 protein on apoptosis induction in goose embryo fibroblast (GEF) cells were examined. Flow cytometry analysis and TUNEL assays revealed that GPV infection and NS1 transfection induced significant apoptosis in GEF cells compared to what was observed in mock-infected cells. Interestingly, the increase in the rate of apoptosis detected in GPV-infected GEFs was accompanied by an increased viral load in the cells. In addition, the apoptotic pathway was mediated by apoptosis-inducing factors (AIFs) and internal factors that influence the release of AIFs. The results indicated that the mitochondrial membrane potential was decreased, and AIF expression was increased in the nucleus (P 0.01). Reactive oxygen species (ROS) increased gradually within 48 h (P 0.001). Cathepsin D activities were also increased (P 0.05). The results demonstrated that the AIF-mediated pathway is a new mitochondrial apoptotic pathway and that mitochondrial depolarization, ROS content, and cathepsin D activities are the key factors influencing apoptosis in GEF cells.

Xiao Lu,1,* Quan-Xing Liu,1,* Jiao Zhang,1 Dong Zhou,1 Gui-Xue Yang,1 Man-Yuan Li,1 Yuan Qiu,2 Qian Chen,3 Hong Zheng,1 Ji-Gang Dai1 1Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, People’s Republic of China; 2Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, People’s Republic of China; 3Cancer Center of Daping Hospital, Army Medical University, Chongqing 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Gang Dai; Hong Zheng Email daijigang@tmmu.edu.cn; ziecoe@163.comBackground: Lung cancer remains the leading cause of cancer-related death worldwide. The human PINK1 gene (PTEN induced kinase 1, Park6), an important gene for Parkinson’s disease, was found to be associated with tumor development although the molecular mechanisms underlying this relationship remain largely unknown.Objective: To analyze the clinical value and molecular mechanism of PINK1 in non-small cell lung cancer (NSCLC).Materials and Methods: Western blot, qRT-PCR and Immunohistochemistry were employed to determine the levels of PINK1 in 87 paired NSCLC tissues, Oncomine and TCGA databases were also used for the evaluation of expression and prognosis of PINK1. The mitophagy, proliferation, migration, invasion, and apoptosis abilities of A549 and H1975 cells were detected, and the autophagy-related proteins in the cells were also determined.Results: Immunohistochemical staining revealed higher PINK1 expression in tumor tissues, which was strongly linked to the tumor-node-metastasis classification. Survival analysis of 1085 NSCLC patients also revealed that low PINK1 expression levels were associated with significantly longer overall survival. Univariate and multivariate analyses indicated that PINK1 expression was an independent predictor of overall survival among patients with NSCLC. We also evaluated the influence of PINK1 deficiency in NSCLC cell lines (A549 and H1975), which revealed significant suppression of migration capability and cell viability, as well as a significantly elevated apoptosis ratio. In cells with stable interference of PINK1 expression, dysfunctional mitochondria accumulated while autophagy was inhibited, which indicated that cell activity suppression was mediated by the accumulation of dysfunctional mitochondria. The suppression of migration and autophagy was reversed in cells that overexpressed PINK1.Conclusion: Our results suggest that PINK1 may be a potential therapeutic target and prognostic biomarker in NSCLC.Keywords: PINK1, NSCLC, mitochondria, autophagy, migration, proliferation

The hippocampus plays an important role in representing spatial locations and sequences and for transforming representations via pattern separation and completion. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci (MOL), a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to fMRI activation patterns revealed that hippocampal subfields contained representations of both temporal context and multiple features of sequence structure, including location identity, distance, and sequence boundaries. Critically, the hippocampal CA1 and CA23DG exhibited spatial and sequential pattern separation, respectively, enabling the encoding of multiple items in the same location and reducing swap errors across adjacent locations. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.

Background: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, causing an unprecedented pandemic. However, there is no specific antiviral therapy for coronavirus disease 2019 (COVID-19). We conducted a clinical trial to compare the effectiveness of three antiviral treatment regimens in patients with mild to moderate COVID-19. Methods: This was a single-center, randomized, open-labeled, prospective clinical trial. Eligible patients with mild to moderate COVID-19 were randomized into three groups: ribavirin (RBV) plus interferon-α (IFN-α), lopinavir/ritonavir (LPV/r) plus IFN-α, and RBV plus LPV/r plus IFN-α at a 1:1:1 ratio. Each patient was invited to participate in a 28-d follow-up after initiation of an antiviral regimen. The outcomes include the difference in median interval to SARS-CoV-2 nucleic acid negativity, the proportion of patients with SARS-CoV-2 nucleic acid negativity at day 14, the mortality at day 28, the proportion of patients re-classified as severe cases, and adverse events during the study period. Results: In total, we enrolled 101 patients in this study. Baseline clinical and laboratory characteristics of patients were comparable among the three groups. In the analysis of intention-to-treat data, the median interval from baseline to SARS-CoV-2 nucleic acid negativity was 12 d in the LPV/r+IFN-α-treated group, as compared with 13 and 15 d in the RBV+IFN-α-treated group and in the RBV+LPV/r+ IFN-α-treated group, respectively (p=0.23). The proportion of patients with SARS-CoV-2 nucleic acid negativity in the LPV/r+IFN-α-treated group (61.1%) was higher than the RBV+ IFN-α-treated group (51.5%) and the RBV+LPV/r+IFN-α-treated group (46.9%) at day 14; however, the difference between these groups was calculated to be statistically insignificant. The RBV+LPV/r+IFN-α-treated group developed a significantly higher incidence of gastrointestinal adverse events than the LPV/r+ IFN-α-treated group and the RBV+ IFN-α-treated group. Conclusions: Our results indicate that there are no significant differences among the three regimens in terms of antiviral effectiveness in patients with mild to moderate COVID-19. Furthermore, the combination of RBV and LPV/r is associated with a significant increase in gastrointestinal adverse events, suggesting that RBV and LPV/r should not be co-administered to COVID-19 patients simultaneously. Clinical Trial Registration: www.ClinicalTrials.gov, ID: ChiCTR2000029387. Registered on January 28, 2019.

Updating old memories with new, more current information is critical for human survival, yet the neural mechanisms for memory updating in general and the effect of retrieval practice in particular are poorly understood. Using a three-day A-B/A-C memory updating paradigm, we found that compared to restudy, retrieval practice could strengthen new A-C memories and reduce old A-B memory intrusion, but did not suppress A-B memories. Neural activation pattern analysis revealed that compared to restudy, retrieval practice led to stronger target representation in the medial prefrontal cortex (MPFC) during the final test. Critically, it was only under the retrieval practice condition that the MPFC showed strong and comparable competitor evidence for both correct and incorrect trials during final test, and that the MPFC target representation during updating was predictive of subsequent memory. These results suggest that retrieval practice is able to facilitate memory updating by strongly engaging MPFC mechanisms in memory integration, differentiation and consolidation.

Although human memories seem unique to each individual, they are shared to a great extent across individuals. Previous studies have examined, separately, subject-specific and cross-subject shared representations during memory encoding and retrieval, but how shared memories are formed from individually encoded representations is not clearly understood. Using a unique fMRI design involving memory encoding and retrieval, and representational similarity analysis to link representations from different individuals, brain regions, and processing stages, the current study revealed that distributed brain regions showed both subject-specific and shared neural representations during both memory encoding and retrieval. Furthermore, different brain regions showed stage-specific representational strength, with the visual cortex showing greater unique and shared representations during encoding, whereas the left angular gyrus showing greater unique and shared representations during retrieval. The neural representations during encoding were transformed during retrieval, as shown by smaller cross-subject encoding-retrieval similarity (ERS) than cross-subject similarity either during encoding or during retrieval. This cross-subject and cross-stage similarity was found both within and across regions, with strong pattern similarity between the encoded representation in VVC and the retrieved representation in the angular gyrus. Simulation analysis further suggested that these patterns could be achieved by incorporating stage-specific representational strength, and cross-region reinstatement from encoding to retrieval, but not by a common transformation from encoding to retrieval across subjects. Together, our results shed light on how memory representations are encoded and transformed to maintain individual characteristics and at the same time to create shared representations to facilitate interpersonal communication.

Background Executive function (EF) is vital to human beings. It has been linked to many genes and family environmental factors in separate studies, but few studies have examined the potential interactions between gene(s) and environmental factor(s). The current study explored the whole genome to identify SNPs, genes, and pathways that interacted with parental warmth (PW) on EF. Results Nine EF tasks were used to measure its three components (common EF, updating, shifting) based on the model proposed by Miyake et al. (2000). We found that rs111605473, LAMP5, SLC4A7, and LRRK1 interacted significantly with PW to affect the updating component of EF, and the GSE43955 pathway interacted significantly with PW to affect the common EF component. Conclusions The current study is the first to identify genes that interacted with PW to affect EF. Further studies are needed to reveal the underlying mechanism.

Previous neuroimaging studies have suggested similar neural activations for word reading in native and second languages. However, such similarities were qualitatively determined (i.e., overlapping activation based on traditional univariate activation analysis). In this study, using representational similarity analysis and an artificial language training paradigm, we quantitatively computed cross-language neural pattern similarity to examine the modulatory effect of proficiency in the new language. Twenty-four native Chinese speakers were trained to learn 30 words in a logographic artificial language for 12 days and scanned while performing a semantic decision task after 4-day training and after 12-day training. Results showed that higher proficiency in the new language was associated with higher cross-language pattern similarity in select regions of the reading network.

Fundamental theories of human cognition have long posited that the short‐term maintenance of actions is supported by one of the “core knowledge” systems of human visual cognition, yet its neural substrates are still not well understood. In particular, it is unclear whether the visual short‐term memory (VSTM) of actions has distinct neural substrates or, as proposed by the spatio‐object architecture of VSTM, shares them with VSTM of objects and spatial locations. In two experiments, we tested these two competing hypotheses by directly contrasting the neural substrates for VSTM of actions with those for objects and locations. Our results showed that the bilateral middle temporal cortex (MT) was specifically involved in VSTM of actions because its activation and its functional connectivity with the frontal–parietal network (FPN) were only modulated by the memory load of actions, but not by that of objects/agents or locations. Moreover, the brain regions involved in the maintenance of spatial location information (i.e., superior parietal lobule, SPL) was also recruited during the maintenance of actions, consistent with the temporal–spatial nature of actions. Meanwhile, the frontoparietal network (FPN) was commonly involved in all types of VSTM and showed flexible functional connectivity with the domain‐specific regions, depending on the current working memory tasks. Together, our results provide clear evidence for a distinct neural system for maintaining actions in VSTM, which supports the core knowledge system theory and the domain‐specific and domain‐general architectures of VSTM.

A fundamental question of human episodic memory concerns the cognitive and neural representations and processes that give rise to the neural signals of memory. By integrating behavioral tests, formal computational models, and neural measures of brain activity patterns, recent studies suggest that memory signals not only depend on the neural processes and representations during encoding and retrieval, but also on the interaction between encoding and retrieval (e.g., transfer-appropriate processing), as well as on the interaction between the tested events and all other events in the episodic memory space (e.g., global matching). In addition, memory signals are also influenced by the compatibility of the event with the existing long-term knowledge (e.g., schema matching). These studies highlight the interactive nature of human episodic memory.

The study of genetic influences on brain connectivity, known as connectome genetics, is an exciting new direction of research in imaging genetics. We here review recent results and current statistical methods in this area, and discuss some of the persistent challenges and possible directions for future work.

The insula plays an important role in response inhibition. Most relevant here, it has been proposed that the dorsal anterior insular cortex (dAIC) plays a central role in a salience network that is responsible for switching between the default mode network and the executive control network. However, the insula’s role in sexually motivated response inhibition has not yet been studied. In the present study, eighty-five 18-30 year-old sexually active men who have sex with men (MSM) performed an erotic Go/NoGo task while in an MRI scanner. Participants’ real-world sexual risk-taking (frequency of condomless anal intercourse over the past 90 days) was then correlated with their neural activity during the task. We found greater activity in bilateral anterior insular cortex (both dorsal and ventral) on contrasts with stronger motivational information (attractive naked male pictures versus pictures of clothed, middle-aged females) and on contrasts requiring greater response inhibition (NoGo versus Go). We also found that activity in the right dAIC was negatively correlated with participants’ real-world sexual risk-taking. Our results confirmed the involvement of the insular cortex in motivated response inhibition. Especially, the decreased right dAIC activity may reduce the likelihood that the executive control network will come online when individuals are faced with situations requiring inhibitory control and thus lead them to make more risky choices.