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Abstract Background To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia. Methods In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses. Results Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P

Chlamydia are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate intracellular replication, these bacteria must engage in host-pathogen interactions to obtain nutrients and membranes required for the growth of the inclusion, thereby sustaining prolonged bacterial colonization. Autophagy is a highly conserved process that delivers cytoplasmic substrates to the lysosome for degradation. Pathogens have developed strategies to manipulate and/or exploit autophagy to promote their replication and persistence. This review delineates recent advances in elucidating the interplay between Chlamydia trachomatis infection and autophagy in recent years, emphasizing the intricate strategies employed by both the Chlamydia pathogens and host cells. Gaining a deeper understanding of these interactions could unveil novel strategies for the prevention and treatment of Chlamydia infection.

ABSTRACTCoxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.

Common airborne allergens (pollen, animal dander and those from fungi and insects) are the main triggers of type I allergic disorder in the respiratory system and are associated with allergic rhinitis, allergic asthma, as well as immunoglobulin E (IgE)-mediated allergic bronchopulmonary aspergillosis. These allergens promote IgE crosslinking, vasodilation, infiltration of inflammatory cells, mucosal barrier dysfunction, extracellular matrix deposition and smooth muscle spasm, which collectively cause remodelling of the airways. Fungus and insect (house dust mite and cockroaches) indoor allergens are particularly rich in proteases. Indeed, more than 40 different types of aeroallergen proteases, which have both IgE-neutralising and tissue-destructive activities, have been documented in the Allergen Nomenclature database. Of all the inhaled protease allergens, 85% are classed as serine protease activities and include trypsin-like, chymotrypsin-like and collagenolytic serine proteases. In this article, we review and compare the allergenicity and proteolytic effect of allergen serine proteases as listed in the Allergen Nomenclature and MEROPS databases and highlight their contribution to allergic sensitisation, disruption of the epithelial barrier and activation of innate immunity in allergic airways disease. The utility of small-molecule inhibitors of allergen serine proteases as a potential treatment strategy for allergic airways disease will also be discussed.

ABSTRACTRickettsia rickettsii (R. rickettsii), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among Rickettsia spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of R. rickettsii remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with R. rickettsii. We found that the expression of TRIM56 was upregulated in the R. rickettsii-infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while R. rickettsii replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-β. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against R. rickettsii in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of R. rickettsii by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF.IMPORTANCEGiven that Rickettsia rickettsii (R. rickettsii) is the most pathogenic member within the Rickettsia genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on R. rickettsii infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in R. rickettsii-infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-β production. Notably, the mutation of the TRIM56’s E3 ligase catalytic site did not impede R. rickettsii replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against R. rickettsii through the modulation of the cGAS-STING signaling pathway.

Abstract Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory modalities, enabling crossmodal memory coding concurrent with modality-dependent coding. In middle age, however, crossmodal coding remarkably diminishes while modality-dependent coding persists, and both types of coding decay in advanced age. Resting-state functional connectivity, especially among memory-coding neurons, decreases already in middle age, suggesting deteriorated recurrent circuits for memory maintenance. Optogenetic inactivation reveals that the middle-aged mPFC exhibits heightened vulnerability to perturbations. These findings elucidate functional alterations of the prefrontal circuit that unfold in middle age and deteriorate further as a hallmark of cognitive aging.

Abstract Background Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. Methods We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. Discussion The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. Trial registration This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Coxiella burnetii is an obligate intracellular bacterium that causes Q fever, a zoonotic disease typically manifests as a severe flu-illness. After invading into the host cells, C. burnetii delivers effectors to regulate the vesicle trafficking and fusion events to form a large and mature Coxiella-containing vacuole (CCV), providing sufficient space and nutrition for its intracellular growth and proliferation. Lysosomal trafficking regulator (LYST) is a member of the Beige and Chediak-Higashi syndrome (BEACH) family, which regulates the transport of vesicles to lysosomes and regulates TLR signaling pathway, but the effect of LYST on C. burnetii infection is unclear. In this study, a series of experiments has been conducted to investigate the influence of LYST on intracellular growth of C. burnetii. Our results showed that lyst transcription was up-regulated in the host cells after C. burnetii infection, but there is no significant change in lyst expression level after infection with the Dot/Icm type IV secretion system (T4SS) mutant strain, while CCVs expansion and significantly increasing load of C. burnetii appeared in the host cells with a silenced lyst gene, suggesting LYST inhibits the intracellular proliferation of C. burnetii by reducing CCVs size. Then, the size of CCVs and the load of C. burnetii in the HeLa cells pretreated with E-64d were significantly decreased. In addition, the level of iNOS was decreased significantly in LYST knockout THP-1 cells, which was conducive to the intracellular replication of C. burnetii. This data is consistent with the phenotype of L-NMMA-treated THP-1 cells infected with C. burnetii. Our results revealed that the upregulation of lyst transcription after infection is due to effector secretion of C. burnetii and LYST inhibit the intracellular replication of C. burnetii by reducing the size of CCVs and inducing nos2 expression.

Abstract Listeria monocytogenes (Lm) is a facultative, intracellular Gram-positive pathogenic bacterium that causes sepsis, a condition characterized by persistent excessive inflammation and organ dysfunction. However, the pathogenesis of Lm-induced sepsis is unknown. In this research, we discovered that TRIM32 is required for innate immune regulation during Lm infection. Trim32 deficiency remarkably reduced bacteremia and proinflammatory cytokine secretion in mice with severe Lm infection, preventing sepsis. Trim32 −/− mice had a lower bacterial burden after Lm infection and survived significantly longer than wild-type (WT) mice, as well as lower serum levels of inflammatory cytokines TNF-α, IL-6, IL-18, IL-12p70, IFN-β, and IFN-γ at 1 day post infection (dpi) compared to WT mice. On the other hand, the chemokines CXCL1, CCL2, CCL7, and CCL5 were enhanced at 3 dpi in Trim32 −/− mice than WT mice, reflecting increased recruitment of neutrophils and macrophages. Furthermore, Trim32 −/− mice had higher levels of macrophage-associated iNOS to kill Lm. Collectively, our findings suggest that TRIM32 reduces innate immune cells recruitment and Lm killing capabilities via iNOS production. Graphical Abstract

Abstract Background Depressive symptoms are highly prevalent among people living with HIV (PLWH). We leveraged Latent Profile Analysis (LPA) to identify profiles of depressive symptoms among PLWHs. We also investigated differences in psychological factors of interest, demographic characteristics, and HIV-related factors across patients’ profiles. Methods A cross-sectional study was conducted at one hospital and two designated prison facilities in Hunan province, China. A total sample of 533 PLWHs (320 recruited from the hospital, 213 recruited from prisons) completed the survey. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Family function, resilience, childhood trauma, demographic characteristics, and HIV-related factors were also evaluated. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for depressive symptoms; 2) identify demographic characteristics, and HIV-related, and psychological factors predicting PLWHs’ likelihood to express a specific profile. Results We identified three distinct profiles of depressive symptoms among PLWHs: severe symptoms (11.8%), moderate symptoms (40.5%), and low/no symptoms (47.7%). Moderate/ severe family dysfunction, low resilience, experiencing emotional abuse and neglect were more likely to fall in the “severe symptoms” rather than the “low/no symptoms” profile. In addition, severe family dysfunction, low resilience, and experiencing emotional neglect indicated a higher likelihood of being classified in the “moderate symptoms” profile, compared to the “low/no symptoms” profile. Conclusion Identifying profiles of depressive symptoms among PLWHs using the PHQ-9 items allows for understanding of the distinct paths of development of depressive symptoms and for developing tailored prevention and intervention programs for PLWHs.

Abstract Background: The association between childhood trauma (CT) and psychotic-like experiences (PLEs) is well-established. Many previous studies have recognized wisdom as a protective factor for mental health, but its role in the relation between CT and PLEs remains unknown. We aimed to investigate the mediating effect of wisdom in the above association among Chinese college students. Methods: We conducted a nationwide survey covering 9 colleges across China and recruited a total of 5873 students using online questionnaires between September 14 and October 18, 2021. Convenience sampling was adopted. We employed the San Diego Wisdom Scale (SD-WISE), the Childhood Trauma Questionnaire (CTQ-28), and the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-15) to measure the wisdom, CT and PLEs, respectively. Descriptive, correlation, and mediation analysis were utilized. Results: The positive correlation between CT and PLEs was well-replicated among college students (Pearson’s r = 0.30, p

Abstract Background Coxiella burnetii (Cb) is the causative agent of the zoonotic disease Q fever which is distributed worldwide. Molecular typing of Cb strains is essential to find out the infectious source and prevent Q fever outbreaks, but there has been a lack of typing data for Cb strains in China. The aim of this study was to investigate the genotypes of Cb strains in wild rats in Yunnan Province, China. Results Eighty-six wild rats (Rattus flavipectus) were collected in Yunnan Province and 8 of the 86 liver samples from the wild rats were positive in Cb-specific quantitative PCR (qPCR). The Cb strains from the 8 rats were then typed into 3 genotypes using 10-spacer multispacer sequence typing (MST), and 2 of the 3 genotypes were recognized as novel ones. Moreover, the Cb strains in the wild rats were all identified as genotype 1 using 6-loci multilocus variable number of tandem repeat analysis (MLVA). Conclusions This is the first report of genotypic diversity of Cb strains from wild rats in China. Further studies are needed to explore the presence of more genotypes and to associate the genotypes circulating in the wildlife-livestock interaction with those causing human disease to further expand on the epidemiological aspects of the pathogen.

Abstract Background Recent genetic evidence implicates glutamatergic-receptor variations in schizophrenia. Glutamatergic excess during early life in people with schizophrenia may cause excitotoxicity and produce structural deficits in the brain. Cortical thickness and gyrification are reduced in schizophrenia, but only a subgroup of patients exhibits such structural deficits. We delineate the structural variations among unaffected siblings and patients with schizophrenia and study the role of key glutamate-receptor polymorphisms on these variations. Methods Gaussian Mixture Model clustering was applied to the cortical thickness and gyrification data of 114 patients, 112 healthy controls, and 42 unaffected siblings to identify subgroups. The distribution of glutamate-receptor (GRM3, GRIN2A, and GRIA1) and voltage-gated calcium channel (CACNA1C) variations across the MRI-based subgroups was studied. The comparisons in clinical symptoms and cognition between patient subgroups were conducted. Results We observed a “hypogyric,” “impoverished-thickness,” and “supra-normal” subgroups of patients, with higher negative symptom burden and poorer verbal fluency in the hypogyric subgroup and notable functional deterioration in the impoverished-thickness subgroup. Compared to healthy subjects, the hypogyric subgroup had significant GRIN2A and GRM3 variations, the impoverished-thickness subgroup had CACNA1C variations while the supra-normal group had no differences. Conclusions Disrupted gyrification and thickness can be traced to the glutamatergic receptor and voltage-gated calcium channel dysfunction respectively in schizophrenia. This raises the question of whether MRI-based multimetric subtyping may be relevant for clinical trials of agents affecting the glutamatergic system.

Abstract Background Medication adherence is a common issue influenced by various factors among patients with severe mental disorders worldwide. However, most literature to date has been primarily quantitative and has focused on medication adherence issue from the perspective of patients or their caregivers. Moreover, research focused on medication adherence issue in China is scarce. Present study aims to explore the influential factors of medication adherence among patients with severe mental disorders form the perspective of mental health professionals in Hunan Province, China. Methods A qualitative study was performed in Hunan Province, China with 31 mental health professionals recruited from October to November 2017. And semi-structured interviews or focus group interviews were conducted along with audio recordings of all interviews. Interview transcripts were then coded and analyzed in Nvivo software with standard qualitative approaches. Results Three major themes influencing medication adherence among patients with severe mental disorders were identified as: (1) attitudes towards mental disorder/treatment; (2) inadequate aftercare; (3) resource shortages. Conclusions This qualitative study identified the factors influencing medication adherence among patients with severe mental disorders in China. As a locally driven research study, it provides practical advice on medication adherence promotion for mental health workers and suggests culturally tailored models that improve the management of patients with severe mental disorders in order to reduce economic burden on individual and societal level.

Abstract Background People living with HIV (PLWH) carry a high risk for mental health problems, which has been extensively reported in the literature. However, an understanding of mental health characteristics in different subgroups of PLWH is still limited. In the present study, we conducted a cross-sectional survey to explore mental health characteristics and their associations with childhood trauma in two major subgroups of PLWH in China. Methods A total of 533 PLWH (213 prisoners in the prison system, and 320 outpatients) were assessed using the 8-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-P8), Generalized Anxiety Disorder scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Childhood Trauma Questionnaire (CTQ). Results From the total sample, 22.0% PLWH frequently experienced psychotic-like experiences (PLEs), 21.8% had clinically significant anxiety syndrome, 34.0% had clinically significant depressive syndrome, and 63.6% experienced at least one type of traumatic exposure during their childhood, with physical neglect being the most common. Compared to outpatients with HIV, prisoners living with HIV reported more severe mental health problems and a higher frequency of childhood trauma, with childhood trauma in turn predicting higher risk for mental health problems. Similarly, among outpatients living with HIV, both childhood emotional and sexual abuse had predictive effects on all the three mental health problems. Conclusions The study suggests that PLWH have higher risk of anxiety, depression and PLEs, and childhood trauma could serve as predicting factors for such risks. In addition, childhood trauma may play distinct roles in predicting the risk for the mental health problems, depending on different subgroup of PLWH.

Self-face recognition is a vital aspect of self-referential processing, which is closely related to affective states. However, neuroimaging research on self-face recognition in adults with major depressive disorder is lacking. This study aims to investigate the alteration of brain activation during self-face recognition in adults with first-episode major depressive disorder (FEMDD) via functional magnetic resonance imaging (fMRI); FEMDD (n = 59) and healthy controls (HC, n = 36) who performed a self-face-recognition task during the fMRI scan. The differences in brain activation signal values between the two groups were analyzed, and Pearson correlation analysis was used to evaluate the relationship between the brain activation of significant group differences and the severity of depressive symptoms and negative self-evaluation; FEMDD showed significantly decreased brain activation in the bilateral occipital cortex, bilateral fusiform gyrus, right inferior frontal gyrus, and right insula during the task compared with HC. No significant correlation was detected between brain activation with significant group differences and the severity of depression and negative self-evaluation in FEMDD or HC. The results suggest the involvement of the malfunctioning visual cortex, prefrontal cortex, and insula in the pathophysiology of self-face recognition in FEMDD, which may provide a novel therapeutic target for adults with FEMDD.

Rickettsia is a genus of nonmotile, Gram-negative, non-spore-forming, highly pleomorphic bacteria that cause severe epidemic rickettsioses. The spotted fever group and typhi group are major members of the genus Rickettsia. Rickettsial species from the two groups subvert diverse host cellular processes, including membrane dynamics, actin cytoskeleton dynamics, phosphoinositide metabolism, intracellular trafficking, and immune defense, to promote their host colonization and intercellular transmission through secreted effectors (virulence factors). However, lineage-specific rickettsiae have exploited divergent strategies to accomplish such challenging tasks and these elaborated strategies focus on distinct host cell processes. In the present review, we summarized current understandings of how different rickettsial species employ their effectors’ arsenal to affect host cellular processes in order to promote their own replication or to avoid destruction.

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91-120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.

Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves’ ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

Chlamydia psittaci is the causative agent of psittacosis, a worldwide zoonotic disease. A rapid, specific, and sensitive diagnostic assay would be benefit for C. psittaci infection control. In this study, an assay combining recombinase-aided amplification and a lateral flow strip (RAA-LF) for the detection of active C. psittaci infection was developed. The RAA-LF assay targeted the CPSIT_RS02830 gene of C. psittaci and could be accomplished in 15 min at a single temperature (39°C). The analytical sensitivity of the assay was as low as 1 × 100 copies/μl and no cross-reaction with some other intracellular pathogens was observed. Moreover, all feces samples from mice infected with C. psittaci at day-1 post-infection were positive in the RAA-LF assay. In conclusion, the RAA-LF assay provides a convenient, rapid, specific and sensitive method for detection of active C. psittaci infection and it is also suitable for C. psittaci detection in field.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has caused a significant impact on the physical and mental health of healthcare workers. This study assessed the psychological status of healthcare workers who were exposed to different risk-levels in China and explored the factors that affected their mental health.MethodsDemographic, occupational characteristics, and mental health measurements were collected from 810 workers in 41 hospitals in China, through online questionnaires from February 11 to March 3, 2020. The degree of symptoms for fatigue, anxiety, and insomnia were assessed using the Chinese versions of the Fatigue Severity Scale, 7-item Generalized Anxiety Disorder Scale, and Insomnia Severity Index, respectively. Binary logistic regression analysis was performed to identify factors associated with mental health symptoms.ResultsAll 810 participants completed the relevant questionnaires without missing data. The prevalence of fatigue, anxiety, and insomnia symptoms was 74.3, 73.7, and 61.7%, respectively. Nurses, women, and workers exposed to high-risk areas were more likely to report mental health problems (P < 0.05). After controlling for confounders, exposure to high-risk areas was independently associated with increased symptoms of fatigue, anxiety, and insomnia (fatigue among high-risk areas: OR, 3.87; 95% CI, 2.26–6.61; P < 0.001; anxiety among high-risk areas: OR, 2.66; 95% CI, 1.58–4.51; P < 0.001; insomnia among high-risk areas: OR, 2.83; 95% CI, 1.68–4.79, P < 0.001).ConclusionThe study demonstrated significant differences in psychological symptoms among healthcare workers exposed to different levels of risk, and those in high-risk areas were more vulnerable to experiencing mental health symptoms. These findings emphasize the importance of giving due attention to healthcare workers, especially women, nurses, and those working in high-risk settings during the COVID-19 pandemic.

It is crucial to accurately identify precious tree pests in a real, complex natural environment in order to monitor the growth of precious trees and provide growers with the information they need to make effective decisions. However, pest identification in real complex natural environments is confronted with several obstacles, including a lack of contrast between the pests and the background, the overlapping and occlusion of leaves, numerous variations in pest size and complexity, and a great deal of image noise. The purpose of the study was to construct a segmentation method for identifying precious tree pests in a complex natural environment. The backbone of an existing Mask region-based convolutional neural network was replaced with a Swin Transformer to improve its feature extraction capability. The experimental findings demonstrated that the suggested method successfully segmented pests in a variety of situations, including shaded, overlapped, and foliage- and branch-obscured pests. The proposed method outperformed the two competing methods, indicating that it is capable of accurately segmenting pests in a complex natural environment and provides a solution for achieving accurate segmentation of precious tree pests and long-term automatic growth monitoring.

Rhipicephalus microplus, a vector that can transmit many pathogens to humans and domestic animals, is widely distributed in Yunnan province, China. However, few reports on the prevalence of tick-borne pathogens (TBPs) in Rh. microplus in Yunnan are available. The aim of this study was to detect TBPs in Rh. microplus in Yunnan and to analyze the phylogenetic characterization of TBPs detected in these ticks. The adult Rh. microplus (n = 516) feeding on cattle were collected. The pooled DNA samples of these ticks were evaluated using metagenomic next-generation sequencing (mNGS) and then TBPs in individual ticks were identified using genus- or group-specific nested polymerase chain reaction (PCR) combined with DNA sequencing assay. As a result, Candidatus Rickettsia jingxinensis (24.61%, 127/516), Anaplasma marginale (13.18%, 68/516), Coxiella burnetii (3.10%, 16/516), and Coxiella-like endosymbiont (CLE) (8.33%, 43/516) were detected. The dual coinfection with Ca. R. jingxinensis and A. marginale and the triple coinfection with Ca. R. jingxinensis, A. marginale, and CLE were most frequent and detected in 3.68% (19/516) and 3.10% (16/516) of these ticks, respectively. The results provide insight into the diversity of TBPs and their coinfections in Rh. microplus in Yunnan province of China, reporting for the first time that C. burnetii had been found in Rh. microplus in China. Multilocus variable number tandem repeat analysis with 6 loci (MLVA-6) discriminated the C. burnetii detected in Rh. microplus in Yunnan into MLVA genotype 1, which is closely related to previously described genotypes found primarily in tick and human samples from different regions of the globe, indicating a potential public health threat posed by C. burnetii in Rh. microplus in Yunnan.

Previous studies have demonstrated that the suicidality in patients with major depressive disorder (MDD) is related to abnormal brain functional connectivity (FC) patterns. However, little is known about its relationship with dynamic functional connectivity (dFC) based on the assumption that brain FCs fluctuate over time. Temporal stabilities of dFCs within the whole brain and nine key networks were compared between 52 MDD patients and 21 age, sex-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging and temporal correlation coefficients. The alterations in MDD were further correlated with the scores of suicidality item in the Hamilton Rating Scale for Depression (HAMD). Compared with HCs, the MDD patients showed a decreased temporal stability of dFC as indicated by a significantly decreased temporal correlation coefficient at the global level, as well as within the default mode network (DMN) and subcortical network. In addition, temporal correlation coefficients of the DMN were found to be significantly negatively correlated with the HAMD suicidality item scores in MDD patients. These results suggest that MDD may be characterized by excessive temporal fluctuations of dFCs within the DMN and subcortical network, and that decreased stability of DMN connectivity may be particularly associated with the suicidality in MDD.

Hyalomma marginatum is an important arthropod vector in the transmission of various zoonoses. The aim of this study was to identify the tick-borne pathogens (TBPs) maintained in Hy. marginatum in Tibet and to estimate the risk of human tick-borne diseases. Adult Hy. marginatum ticks (n = 14) feeding on yaks were collected. The individual DNA samples of these ticks were sequenced with metagenomic next-generation sequencing to survey the presence of TBPs. TBPs in individual ticks were identified with nested polymerase chain reaction (PCR) combined with DNA sequencing. The presence of Rickettsia , Anaplasma , and Ehrlichia in individual ticks was indicated by the taxonomic profiles at the genus level, but only Rickettsia aeschlimannii (100%, 13/13) was further detected in the ticks by nested PCR. This study provides information on the microbial communities of Hy. marginatum in Tibet, China, and provides the first report of R. aeschlimannii found in Hy. marginatum in Tibet. The results of this study indicated that yaks in Tibet are exposed to R. aeschlimannii .

Passive acoustic sensor-based soundscape analysis has become an increasingly important ecological method for evaluation of ecosystem conditions using acoustic indices. Understanding the soundscape composition and correlations between acoustic indices and species richness of birds, the most important sound source in the ecosystem, are of great importance for measuring biodiversity and the level of anthropogenic disturbance. In this study, based on yearlong sound data obtained from five acoustic sensors deployed in Dalongtan, Shennongjia National Park, we analyzed the soundscape composition by comparing the distributions of the soundscape power in different frequency ranges, and examined the correlations between acoustic indices and bird species richness by means of the Spearman rank correlation coefficient method. The diurnal dynamic characteristics of acoustic indices in different seasons were also described. Results showed that the majority of sounds were in the frequency of 2–8 kHz, in which over 50% sounds were in 2–6 kHz, commonly considered the bioacoustic frequency range. The Acoustics Complexity Index, Bioacoustic Index, and Normalized Difference Soundscape Index were significantly correlated with bird species richness, suggesting that these indices can be used for evaluation of bird species richness; Apparent diurnal dynamic patterns of bird acoustic activities were observed in spring, summer, and autumn; however, the intensity and duration of bird acoustic activities in summer is larger/longer than in spring and autumn.

BackgroundThe efficacy or tolerability of paliperidone extended release (ER) in the treatment of methamphetamine (METH)-associated psychosis (MAP) is unknown. This study was designed to assess the tolerability and efficacy of paliperidone ER and risperidone for the treatment of MAP in China.MethodsThis 25-day randomized clinical trial involved 120 patients with acute MAP symptoms who were randomized to receive either paliperidone ER or risperidone from baseline to day 25 of an inpatient hospital stay. The primary outcome was changes in the severity of psychosis, which were assessed using the Positive and Negative Syndrome Scale (PANSS) total score changes from baseline to endpoint.ResultsOverall, 84% of the patients completed the entire study protocol. The PANSS total score, the Clinical Global Impressions-Severity of Illness scale (CGI-S) score, and a METH craving score assessed by a visual analog scale (VAS) showed statistically significant improvements from baseline for the patients in both groups (p < 0.01). The Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS) scores increased from baseline during treatment in both groups (p < 0.01); there were statistically significant differences between the treatment groups in the SAS scores (p < 0.01). Measures of hypermyotonia, salivation, and dizziness were significantly higher in the risperidone-treated patients than in the paliperidone ER-treated patients (all p < 0.05).ConclusionPaliperidone ER and risperidone had similar efficacy and were generally tolerable in the treatment of MAP; however, paliperidone ER had a more favorable adverse event profile than risperidone, particularly regarding extrapyramidal and prolactin-increasing effects.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01822730. Full date of first registration:03/28/2013.

Background: Aberrant functional and structural connectivity across multiple brain networks have been reported in bipolar disorder (BD). However, most previous studies consider the functional and structural alterations in isolation regardless of their possible integrative relationship. The present study aimed to identify the brain connectivity alterations in BD by capturing the latent nexus in multimodal neuroimaging data.Methods: Structural and resting-state images were acquired from 83 patients with BD and 94 healthy controls (HCs). Combined with univariate methods conducted to detect the dysconnectivity in BD, we also employed a semi-multimodal fusion framework fully utilizing the interrelationship between the two modalities to distinguish patients from HCs. Moreover, one-way analysis of variance was adopted to explore whether the detected dysconnectivity has differences across stages of patients with BD.Results: The semi-multimodal fusion framework distinguished patients from HCs with 81.47% accuracy, 85.42% specificity, and 74.75% sensitivity. The connection between the anterior cingulate cortex (ACC) and superior medial prefrontal cortex (sMPFC) contributed the most to BD diagnosis. Consistently, the univariate method also identified that this ACC–sMPFC functional connection significantly decreased in BD patients compared to HCs, and the significant order of the dysconnectivity is: depressive episode < HCs and remission episode < HCs.Conclusions: Our findings, by adopting univariate and multivariate analysis methods, shed light on the decoupling within the anterior midline brain in the pathophysiology of BD, and this decoupling may serve as a trait marker for this disease.

Epithelial barrier dysfunction, characteristic of allergic airway disease may be, at least in part, due to the action of allergen-associated protease activities. Cockroach allergy is a major global health issue, with cockroaches containing considerable serine trypsin-like protease (TLP) activity. The present study sought to evaluate two novel protease inhibitors (PE-BBI and pLR-HL), recently isolated from amphibian skin secretions, for their potential to neutralise cockroach TLP activity and to determine any protective effect on cockroach-induced airway epithelial barrier disruption. Inhibitor potencies against the cockroach-associated activities were determined using a fluorogenic peptide substrate-based activity assay. 16HBE14o- cells (16HBE; a bronchial epithelial cell line) were treated with cockroach extract (CRE) in the presence or absence of the compounds in order to assess cell viability (RealTime Glo luminescent assay) and epithelial barrier disruption (transepithelial resistance and paracellular dextran flux). PE-BBI potently and selectively inhibited CRE TLP activity (pIC50 -8), but not host (16HBE) cell surface activity, which conferred protection of 16HBE cells from CRE-induced cell damage and barrier disruption. Novel protease inhibitor strategies such as PE-BBI may be useful for the treatment of allergic airway disease caused by cockroach proteases.

Objective: The study was aimed to investigate the possible associations among suicidal ideation, brain white matter (WM) integrity and cognitive deficit in first-episode schizophrenia (FES) using diffusion tensor imaging.Methods: The sample contained 18 FES patients with suicidal ideation (SI+), 45 FES patients without suicidal ideation (SI–) and 44 healthy controls. The Calgary Depression Scale for Schizophrenia was used to measure the suicidal ideation and depression symptoms. The whole brain WM integrity and three domains of cognitive function: working memory, verbal comprehension as well as processing speed were compared between the three groups.Results: Compared with SI–, SI+ showed preserved WM integrity as indicated by significantly higher factional anisotropy (FA) or lower mean diffusivity (MD) in multiple WM tracts, and higher FA coupled with lower MD in bilateral posterior corona radiata. Compared with SI−, SI+ were more depressed and had less cognitive deficit in working memory and verbal comprehension. The fiber tracts in bilateral posterior corona radiata connect to the precuneus as shown by probabilistic tractography, and their WM integrity disruptions were found to be positively associated with the cognitive deficits in the FES patients.Discussion: Preserved WM integrity may be a risk factor for suicidal ideation in FES patients. One possible explanation is that it contributes to preserved cognitive function, especially in working memory and verbal comprehension, which may be associated with greater insight and could lead to increased depression and suicidal ideation. The posterior corona radiata and the precuneus may be linked to the related biological processes.

Background: Localized abnormalities in the synchrony of spontaneous neuronal activity, measured with regional homogeneity (ReHo), has been consistently reported in patients with schizophrenia (SCZ) and their unaffected siblings. To date, little is known about the genetic influences affecting the spontaneous neuronal activity in SCZ. DISC1, a strong susceptible gene for SCZ, has been implicated in neuronal excitability and synaptic function possibly associated with regional spontaneous neuronal activity. This study aimed to examine the effects of DISC1 variations on the regional spontaneous neuronal activity in SCZ.Methods: Resting-state fMRI data were obtained from 28 SCZ patients and 21 healthy controls (HC) for ReHo analysis. Six single nucleotide polymorphisms (SNPs) of DISC1 gene were genotyped using the PCR and direct sequencing.Results: Significant diagnosis × genotype interactions were noted for three SNPs (rs821616, rs821617, and rs2738880). For rs821617, the interactions were localized to the precuneus, basal ganglia and pre-/post-central regions. Significant interactive effects were identified at the temporal and post-central gyri for rs821616 (Ser704Cys) and the inferior temporal gyrus for rs2738880. Furthermore, post-hoc analysis revealed that the DISC1 variations on these SNPs exerted different influences on ReHo between SCZ patients and HC.Conclusion: To our knowledge this is the first study to unpick the influence of DISC1 variations on spontaneous neuronal activity in SCZ; Given the emerging evidence that ReHo is a stable inheritable phenotype for schizophrenia, our findings suggest the DISC1 variations are possibly an inheritable source for the altered ReHo in this disorder.