Robust Federated Learning: Maximum Correntropy Aggregation Against Byzantine Attacks.

As an emerging decentralized machine learning technique, federated learning organizes collaborative training and preserves the privacy and security of participants. However, untrustworthy devices, typically Byzantine attackers, pose a significant challenge to federated learning since they can upload malicious parameters to corrupt the global model. To defend against such attacks, we propose a novel robust aggregation method-maximum correntropy aggregation (MCA), which applies the maximum correntropy criterion (MCC) to derive a central value from parameters. Different from the previous use of MCC for denoising, we utilize it as a similarity metric to measure parameter distribution and aggregate a robust center. Correntropy in MCC, with all even-order moments of the parameter, contains high-order statistical properties, which allows for a comprehensive capture of parameter characteristics, thus helping to prevent interference from attackers. Meanwhile, correntropy extracts information from the parameters themselves, without requiring the proportion of malicious attackers. Through the fixed-point iteration, we solve the optimization objective, demonstrating the linear convergence of the iteration formula. Theoretical analysis reveals the robustness aggregation property of MCA and the error bound between MCA and the global optimal solution, with linear convergence to the optimal solution neighborhood. By performing independent identically distribution (IID) and non-IID experiments on three different datasets, we show that MCA exhibits significant robustness under mainstream attacks, whereas other methods cannot withstand all of them.

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1.

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

Establishment of a human organoid-based evaluation system for assessing interspecies infection risk of animal-borne coronaviruses.

The COVID-19 pandemic presents a major threat to global public health. Several lines of evidence have shown that the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), along with two other highly pathogenic coronaviruses, SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV) originated from bats. To prevent and control future coronavirus outbreaks, it is necessary to investigate the interspecies infection and pathogenicity risks of animal-related coronaviruses. Currently used infection models, including in vitro cell lines and in vivo animal models, fail to fully mimic the primary infection in human tissues. Here, we employed organoid technology as a promising new model for studying emerging pathogens and their pathogenic mechanisms. We investigated the key host-virus interaction patterns of five human coronaviruses (SARS-CoV-2 original strain, Omicron BA.1, MERS-CoV, HCoV-229E, and HCoV-OC43) in different human respiratory organoids. Five indicators, including cell tropism, invasion preference, replication activity, host response and virus-induced cell death, were developed to establish a comprehensive evaluation system to predict coronavirus interspecies infection and pathogenicity risks. Using this system, we further examined the pathogenicity and interspecies infection risks of three SARS-related coronaviruses (SARSr-CoV), including WIV1 and rRsSHC014S from bats, and MpCoV-GX from pangolins. Moreover, we found that cannabidiol, a non-psychoactive plant extract, exhibits significant inhibitory effects on various coronaviruses in human lung organoid. Cannabidiol significantly enhanced interferon-stimulated gene expression but reduced levels of inflammatory cytokines. In summary, our study established a reliable comprehensive evaluation system to analyse infection and pathogenicity patterns of zoonotic coronaviruses, which could aid in prevention and control of potentially emerging coronavirus diseases.

Cooperative Time-Varying Formation Fuzzy Tracking Control of Multiple Heterogeneous Uncertain Marine Surface Vehicles With Actuator Failures.

This article addresses the cooperative time-varying formation fuzzy tracking control problem for a cluster of heterogeneous multiple marine surface vehicles subject to unknown nonlinearity and actuator failures. The proposed cooperative control scheme consists of two parts: 1) a distributed time-varying formation observer and 2) a decentralized adaptive fuzzy tracking controller. The distributed observer is designed to obtain a predefined time-varying formation pattern under a directed communication topology. Subsequently, based on the states of the distributed observer, a decentralized fuzzy tracking control law is developed using fuzzy-logic systems and the adaptive approach. Lyapunov functions are constructed to guarantee that the controlled marine vehicles attain the desired time-varying formation with asymptotical stability of tracking errors. Finally, simulation results are presented to validate the efficacy of the proposed control methodology.

Semantic Consistency Reasoning for 3-D Object Detection in Point Clouds.

Point cloud-based 3-D object detection is a significant and critical issue in numerous applications. While most existing methods attempt to capitalize on the geometric characteristics of point clouds, they neglect the internal semantic properties of point and the consistency between the semantic and geometric clues. We introduce a semantic consistency (SC) mechanism for 3-D object detection in this article, by reasoning about the semantic relations between 3-D object boxes and its internal points. This mechanism is based on a natural principle: the semantic category of a 3-D bounding box should be consistent with the categories of all points within the box. Driven by the SC mechanism, we propose a novel SC network (SCNet) to detect 3-D objects from point clouds. Specifically, the SCNet is composed of a feature extraction module, a detection decision module, and a semantic segmentation module. In inference, the feature extraction and the detection decision modules are used to detect 3-D objects. In training, the semantic segmentation module is jointly trained with the other two modules to produce more robust and applicable model parameters. The performance is greatly boosted through reasoning about the relations between the output 3-D object boxes and segmented points. The proposed SC mechanism is model-agnostic and can be integrated into other base 3-D object detection models. We test the proposed model on three challenging indoor and outdoor benchmark datasets: ScanNetV2, SUN RGB-D, and KITTI. Furthermore, to validate the universality of the SC mechanism, we implement it in three different 3-D object detectors. The experiments show that the performance is impressively improved and the extensive ablation studies also demonstrate the effectiveness of the proposed model.

JNMR: Joint Non-Linear Motion Regression for Video Frame Interpolation.

Video frame interpolation (VFI) aims to generate predictive frames by motion-warping from bidirectional references. Most examples of VFI utilize spatiotemporal semantic information to realize motion estimation and interpolation. However, due to variable acceleration, irregular movement trajectories, and camera movement in real-world cases, they can not be sufficient to deal with non-linear middle frame estimation. In this paper, we present a reformulation of the VFI as a joint non-linear motion regression (JNMR) strategy to model the complicated inter-frame motions. Specifically, the motion trajectory between the target frame and multiple reference frames is regressed by a temporal concatenation of multi-stage quadratic models. Then, a comprehensive joint distribution is constructed to connect all temporal motions. Moreover, to reserve more contextual details for joint regression, the feature learning network is devised to explore clarified feature expressions with dense skip-connection. Later, a coarse-to-fine synthesis enhancement module is utilized to learn visual dynamics at different resolutions with multi-scale textures. The experimental VFI results show the effectiveness and significant improvement of joint motion regression over the state-of-the-art methods. The code is available at https://github.com/ruhig6/JNMR.

N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry.

IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

Identification of TMEM53 as a novel SADS-CoV restriction factor that targets viral RNA-dependent RNA polymerase.

ABSTRACTZoonotic transmission of coronaviruses (CoVs) poses a serious public health threat. Swine acute diarrhea syndrome coronavirus (SADS-CoV), originating from a bat HKU2-related CoV, causes devastating swine diseases and poses a high risk of spillover to humans. Currently, licensed therapeutics that can prevent potential human outbreaks are unavailable. Identifying the cellular proteins that restrict viral infection is imperative for developing effective interventions and therapeutics. We utilized a large-scale human cDNA screening and identified transmembrane protein 53 (TMEM53) as a novel cell-intrinsic SADS-CoV restriction factor. The inhibitory effect of TMEM53 on SADS-CoV infection was found to be independent of canonical type I interferon responses. Instead, TMEM53 interacts with non-structural protein 12 (NSP12) and disrupts viral RNA-dependent RNA polymerase (RdRp) complex assembly by interrupting NSP8-NSP12 interaction, thus suppressing viral RdRp activity and RNA synthesis. Deleting the transmembrane domain of TMEM53 resulted in the abrogation of TMEM53-NSP12 interaction and TMEM53 antiviral activity. Importantly, TMEM53 exhibited broad antiviral activity against multiple HKU2-related CoVs. Our findings reveal a novel role of TMEM53 in SADS-CoV restriction and pave the way to host-directed therapeutics against HKU2-related CoV infection.

Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

The JASMONATE ZIM-domain-OPEN STOMATA1 cascade integrates jasmonic acid and abscisic acid signaling to regulate drought tolerance by mediating stomatal closure in poplar.

Drought, which directly affects the yield of crops and trees, is a natural stress with a profound impact on the economy. Improving water use efficiency (WUE) and drought tolerance are relatively effective strategies to alleviate drought stress. OPEN STOMATA1 (OST1), at the core of abscisic acid (ABA) signaling, can improve WUE by regulating stomatal closure and photosynthesis. Methyl jasmonate (MeJA) and ABA crosstalk is considered to be involved in the response to drought stress, but the detailed molecular mechanism is insufficiently known. Here, Populus euphratica, which naturally grows in arid and semiarid regions, was selected as the species for studying MeJA and ABA crosstalk under drought. A yeast two-hybrid assay was performed using PeOST1 as bait and a nucleus-localized factor, JASMONATE ZIM-domain protein 2 (PeJAZ2), was found to participate in MeJA signaling by interacting with PeOST1. Overexpression of PeJAZ2 in poplar notably increased water deficit tolerance and WUE in both severe and mild drought stress by regulating ABA signaling rather than ABA synthesis. Furthermore, a PeJAZ2 overexpression line was shown to have greater ABA-induced stomatal closure and hydrogen peroxide (H2O2) production. Collectively, this evidence establishes a mechanism in which PeJAZ2 acts as a positive regulator in response to drought stress via ABA-induced stomatal closure caused by H2O2 production. Our study presents a new insight into the crosstalk of ABA and jasmonic acid signaling in regulating WUE and drought stress, providing a basis of the drought tolerance mechanism of P. euphratica.

Study on Residual Stress and Optimization of Welding Parameters in Linear Friction Welding of TC17 Titanium Alloy.

Linear friction welding (LFW) is a kind of advanced manufacturing technology and used mainly in the manufacturing of aircraft engine bladed disks (blisks) currently. However, the residual stress evolution of TC17 titanium alloy during LFW is complex and its distribution is difficult to characterize. In this study, the residual stress of welding was studied using numerical simulation and experimental methods. The results showed that the maximum temperature on the welded surface was up to 1000 °C and the cooling rates in the lengthwise, widthwise, and normal direction with the same distance from the center of the weld were 456 °C/s, 448 °C/s, and 232 °C/s, respectively. The lengthwise stress on the welding surface was the largest, followed by the widthwise stress and normal stress. Among the three factors affecting welding stress, the upsetting force played a leading role, followed by the vibration amplitude and frequency of the welded parts. By optimizing the process parameters: upsetting force 18.2 kN, vibration amplitude 2.5 mm, vibration frequency 40 Hz, a 30% decrease of the maximum residual stress could be achieved compared to that without optimization. The residual stress before and after welding parameter optimization was measured by the contour method, and the measured results were in good agreement with the simulation results, which verified the effectiveness of parameter optimization on residual stress controlling.

A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern.

The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broad-spectrum protection against the initial infection and thereby curb the transmission potential. Here, we designed a chimeric triple-RBD immunogen, 3Ro-NC, harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold. 3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern. Notably, intranasal immunization with 3Ro-NC plus the mucosal adjuvant KFD (3Ro-NC + KFDi.n) elicits coordinated mucosal IgA and higher neutralizing antibody specificity (closer antigenic distance) against the Omicron variant. In Omicron-challenged human ACE2 transgenic mice, 3Ro-NC + KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung (85.7-fold) and the nasal turbinate (13.6-fold). Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies. Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection, pathology and transmission potential.

Lethal Swine Acute Diarrhea Syndrome Coronavirus Infection in Suckling Mice.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently emerging bat-borne coronavirus responsible for high mortality rates in piglets. In vitro studies have indicated that SADS-CoV has a wide tissue tropism in different hosts, including humans. However, whether this virus potentially threatens other animals remains unclear. Here, we report the experimental infection of wild-type BALB/c and C57BL/6J suckling mice with SADS-CoV. We found that mice less than 7 days old are susceptible to the virus, which caused notable multitissue infections and damage. The mortality rate was the highest in 2-day-old mice and decreased in older mice. Moreover, a preliminary neuroinflammatory response was observed in 7-day-old SADS-CoV-infected mice. Thus, our results indicate that SADS-CoV has potential pathogenicity in young hosts. IMPORTANCE SADS-CoV, which likely has originated from bat coronaviruses, is highly pathogenic to piglets and poses a threat to the swine industry. Little is known about its potential to disseminate to other animals. No efficient treatment is available, and the quarantine strategy is the only preventive measure. In this study, we demonstrated that SADS-CoV can efficiently replicate in suckling mice younger than 7 days. In contrast to infected piglets, in which intestinal tropism is shown, SADS-CoV caused infection and damage in all murine tissues evaluated in this study. In addition, neuroinflammatory responses were detected in some of the infected mice. Our work provides a preliminary cost-effective model for the screening of antiviral drugs against SADS-CoV infection.

The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.

USP18 contributes to the proliferation and migration of ovarian cancer cells by regulating the AKT/mTOR signaling pathway.

Ubiquitin-specific peptidase (USP)18 is elevated in tumor tissues and is associated with tumor malignancy. USP18 functions as an oncogene in different cancers. However, the role of USP18 in ovarian cancer was poorly understood. TCGA database showed that USP18 was elevated in ovarian cancer tissues. Additionally, USP18 mRNA and protein expression was also up-regulated in tumor tissues. The functional assays were then designed via siRNA-mediated knockdown of USP18. The results showed that knockdown of USP18 reduced cell viability and ovarian cancer proliferation. Furthermore, cell apoptosis was promoted by USP18 silencing, and interference of USP18 suppressed cell migration and invasion. The expression of phosphorylated AKT (p-AKT) and p-mTOR protein was decreased in ovarian cancer cells by USP18 knockdown. Inhibition of AKT attenuated the decrease in cell apoptosis induced by USP18 overexpression and increased cell viability and migration. In conclusion, USP18 promoted the proliferation and migration of ovarian cancer cells by activating AKT/mTOR signaling.

Predictive role of blood eosinophils in adult varicella patients.

The study aimed to explore the relationship between eosinophils and the prognosis of varicella in adults. We retrospectively reviewed the medical records of patients who were hospitalised in The Fifth People's Hospital of Suzhou with a diagnosis of adult varicella during the period between 1 January 2012 and 31 December 2020. Of the 359 patients, 228 (63.51%) had eosinopenia. The proportion of patients with mild type disease was significantly lower in the eosinopenia group than that in the non-eosinopenia group (50.44% vs. 65.65%, P = 0.006). The proportion of the patients with common type disease was significantly higher in the eosinopenia group than that in the non-eosinopenia group (39.47% vs. 28.24%, P = 0.039). The proportion of the patients with severe type disease was higher in the eosinopenia group, although the difference did not reach statistical significance (10.09% vs. 6.11%, P = 0.243). The rates of high fever (47.81% vs. 32.82%, P = 0.008; relative risk (RR) 1.296, 95% confidence interval (CI) 1.091-1.540), headache (43.42% vs. 22.14%, P < 0.001; RR 1.415, 95% CI 1.233-1.623), anorexia (53.51% vs. 35.88%, P = 0.001; RR 1.367, 95% CI 1.129-1.655) and complications (82.89% vs. 64.12%, P < 0.001; RR 2.106, 95% CI 1.460-3.038) were also significantly higher in the eosinopenia group. Among the complications, the liver injury and skin infection were more serious in the eosinopenia group. The disease course was significantly longer in the eosinopenia group than that in the non-eosinopenia group (9.43 ± 1.89 days vs. 8.73 ± 1.25 days, P < 0.001). The improvement rate of liver injury in the recovery period was lower in the eosinopenia group than that in the non-eosinopenia group (35.38% vs. 50%, P = 0.012). The study found that adult varicella patients with eosinopenia had a more serious condition, a higher morbidity of complications and a slower recovery. Blood eosinophils can be used as a new predictor of the severity of adult varicella.