Validation of the personal suicide stigma questionnaire among adolescents with suicide attempts in mainland China.

Objectives: The study aimed to translate and culturally adapt the personal suicide stigma questionnaire (PSSQ) into simplified Chinese and evaluate its psychometric properties among adolescents who have attempted suicide in mainland China. Methods: Following Brislin's translation model and using purposive sampling, we surveyed 440 adolescents who had attempted suicide at Hangzhou Seventh People's Hospital in Zhejiang Province, China. Content validity was determined by a panel of experts, and the construct validity of the scale was assessed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity, and discriminant validity. Reliability analysis was evaluated using Cronbach's α coefficient, test-retest reliability, and half-split reliability. Results: The Chinese version of the PSSQ consists of three dimensions and 14 items. After two rounds of expert consultation, the item-content validity index for all items exceeded 0.70, and the scale-content validity index exceeded 0.90. EFA extracted three factors and retained all 14 items. The CFA indicators demonstrated a good fit. The Cronbach's α coefficient of the scale was 0.880, the half-split reliability was 0.681, and the test-retest reliability was 0.862. It is evident that the PSSQ and its subscales demonstrate stable structural validity and good internal consistency in measuring self-stigma among individuals with suicidal tendencies, indicating that the PSSQ is a reliable tool for assessing the degree of personal stigma in Chinese adolescents who have attempted suicide. Conclusion: This study ensured the linguistic and cultural appropriateness of the Chinese version of the PSSQ through cross-cultural adaptation and validation of its reliability and validity, thereby enhancing the accuracy and reliability of assessing personal stigma among Chinese adolescents who have attempted suicide. The validation of the Chinese version of the scale not only enriches the research tools available for studying personal stigma related to suicide in mainland China, but also provides a reliable quantitative tool for future research on the psychological states of individuals who have attempted suicide, the impact of stigma, and the effectiveness of interventions.

Identification of neurological complications in childhood influenza: a random forest model.

BACKGROUND: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1-2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). OBJECTIVE: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. METHODS: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. RESULTS: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. CONCLUSION: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.

Idebenone Exerts anti-Triple Negative Breast Cancer Effects via Dual Signaling Pathways of GADD45 and AMPK.

Idebenone, a mitochondrial regulator, has exhibited anti-cancer activity in neurogenic and prostate tumor cells; however, its efficacy and specific targets in the treatment of triple-negative breast cancer (TNBC) remain unclear. This study aims to evaluate the potential of Idebenone as a therapeutic agent for TNBC. TNBC cell lines and Xenograft mouse models were used to assess the effect of Idebenone on TNBC both in vitro and in vivo. To investigate the underlying mechanism of Idebenone's effect on TNBC, cell viability assay, transwell invasion assay, cell cycle analysis, apoptosis assay, mitochondrial membrane potential assay, immunofluorescence staining, and transcriptome sequencing were utilized. The results showed that Idebenone impeded the proliferation, colony formation, migration, and invasion of TNBC cells, suppressed apoptosis, and halted the cell cycle in the G2/M phase. The inhibitory effect of Idebenone on TNBC was associated with the GADD45/CyclinB/CDK1 signaling pathway. By disrupting the mitochondrial membrane potential (MMP) and promoting mitophagy, Idebenone promoted cell autophagy through the AMPK/mTOR pathway, thus further suppressing the proliferation of TNBC cells. Furthermore, we found that Idebenone inhibited the development of TNBC in vivo. In conclusion, Idebenone may be a promising therapeutic option for TNBC as it is capable of inducing autophagy and apoptosis.

Clinical characteristics and follow-up of children with norovirus-associated benign convulsions with mild gastroenteritis.

OBJECTIVE: Explore the clinical characteristics and prognosis of children with norovirus (NoV)-associated benign convulsions with mild gastroenteritis (CwG). METHODS: We retrospectively analyzed the Clinical and laboratory data of children with NoV-associated CwG admitted to the emergency department of Guangzhou Children's Hospital between January 2019 and January 2020. And patients were followed up for 23-36 months. RESULTS: There are 49 cases met the CwG criteria. Vomiting was the first symptom in 31 (63.3%) patients, and vomiting could be the main or the only gastrointestinal symptom. The mean frequency of seizures was 3.8 ± 2.4 episodes. Most patients (95.9%) experienced seizures that lasted for less than 5 min. Of the 43 (87.8%) cases followed up from 23 to 36 months, only one experienced recurrent convulsions (after rotavirus infection). SIGNIFICANCE: NoV-associated CwG patients were prone to experiencing more convulsions. However, because most NoV-associated CwG patients had good prognosis, long-term use of anticonvulsants are unnecessary.

SARS-CoV-2 NSP13 interacts with host IRF3, blocking antiviral immune responses.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to human health since late 2019. Notably, the progression of the disease is associated with impaired antiviral interferon (IFN) responses. Although multiple viral proteins were identified as potential IFN antagonists, the underlying molecular mechanisms remain to be fully elucidated. In this study, we firstly demonstrate that SARS-CoV-2 NSP13 protein robustly antagonizes IFN response induced by the constitutively active form of transcription factor IRF3 (IRF3/5D). This induction of IFN response by IRF3/5D is independent of the upstream kinase, TBK1, a previously reported NSP13 target, thus indicating that NSP13 can act at the level of IRF3 to antagonize IFN production. Consistently, NSP13 exhibits a specific, TBK1-independent interaction with IRF3, which, moreover, is much stronger than that of NSP13 with TBK1. Furthermore, the NSP13-IRF3 interaction was shown to occur between the NSP13 1B domain and IRF3 IRF association domain (IAD). In agreement with the strong targeting of IRF3 by NSP13, we then found that NSP13 blocks IRF3-directed signal transduction and antiviral gene expression, counteracting IRF3-driven anti-SARS-CoV-2 activity. These data suggest that IRF3 is likely to be a major target of NSP13 in antagonizing antiviral IFN responses and provide new insights into the SARS-CoV-2-host interactions that lead to viral immune evasion.

Effects of Mud Content on the Setting Time and Mechanical Properties of Alkali-Activated Slag Mortar.

High mud content in the sand has a negative impact on cement mortar but there is little research on Alkali-activated slag (AAS) mortar. In order to explore the impacts of mud content in the sand on the performance of AAS mortar, this paper used sand that contains silt, clay, and a mixture of silt and clay; tested the setting time of AAS with different mud contents of 0%, 2%, 4%, 6%, 8%, and 10%; and measured the unconfined compressive strength and beam flexural strength of 3 d, 7 d, and 28 d AAS mortar specimens. The microstructure of AAS mortar with different kinds of mud was observed by scanning electron microscope (SEM), the elemental composition of the hydration product was tested by energy dispersive spectroscopy (EDS), and the AAS interaction mechanism with different kinds of mud was analyzed. The main conclusions are: the higher the mud content in the sand, the shorter the initial setting time and the longer the final setting time of AAS, mainly because the mud in the sand affects the hydration process; mud content above 4% causes a rapid decrease in the compressive and flexural strengths of AAS mortar, mainly because the mud affects the hydration process and hinders the bonding of the hydration product with the sand. When there is no mud in the sand, the main hydration product of AAS is dense calcium-alumina-silicate-hydrate (C-A-S-H) gel. When the sand contains silt, the hydration product of AAS is loose C-A-S-H gel. When the sand contains clay, the hydration products of AAS contain C-A-S-H gel and a small amount of sodium-aluminum-silicate-hydrate (N-A-S-H), and needle-like crystals. Loose gel and crystals have a negative effect on the AAS mortar strength.

Effects of Borax, Sucrose, and Citric Acid on the Setting Time and Mechanical Properties of Alkali-Activated Slag.

The setting time of alkali-activated slag (AAS) binders is extremely short, while traditional retarders of Portland cement may be invalid for AAS. To find an effective retarder with a less negative impact on strength, borax (B), sucrose (S), and citric acid (CA) were selected as potential retarders. The setting time of AAS with different admixtures dosages of 0%, 2%, 4%, 6%, and 8%, and the unconfined compressive strength and beam flexural strength of 3 d, 7 d, and 28 d AAS mortar specimens were tested. The microstructure of AAS with different additives was observed by scanning using an electron microscope (SEM), and the hydration products were analyzed by energy dispersive spectroscopy (EDS), X-ray diffraction analysis (XRD), and thermogravimetric analysis (DT-TGA) to explain the retarding mechanism of AAS with different additives. The results showed that the incorporation of borax and citric acid could effectively prolong the setting time of AAS more than that of sucrose, and the retarding effect is more and more obvious with the increase in borax and citric acid dosages. However, sucrose and citric acid negatively influence AAS's unconfined compressive strength and flexural stress. The negative effect becomes more evident with the increase in sucrose and citric acid dosages. Borax is the most suitable retarder for AAS among the three selected additives. SEM-EDS analysis showed that the incorporation of borax does three things: produces gels, covers the surface of the slag, and slows down the hydration reaction rate.

SFTS bunyavirus NSs protein sequestrates mTOR into inclusion bodies and deregulates mTOR-ULK1 signaling, provoking pro-viral autophagy.

Autophagy is emerging as a critical player in host defense against diverse infections, in addition to its conserved function to maintain cellular homeostasis. Strikingly, some pathogens have evolved strategies to evade, subvert or exploit different steps of the autophagy pathway for their lifecycles. Here, we present a new viral mechanism of manipulating autophagy for its own benefit with severe fever with thrombocytopenia syndrome bunyavirus (SFTSV, an emerging high-pathogenic virus) as a model. SFTSV infection triggers autophagy, leading to complete autophagic flux. Mechanistically, we show that the nonstructural protein of SFTSV (NSs) interacts with mTOR, the pivotal regulator of autophagy, by targeting its kinase domain and captures mTOR into viral inclusion bodies (IBs) induced by NSs itself. Furthermore, NSsimpairs mTOR-mediated phosphorylation of unc-51-like kinase 1 (ULK1) at Ser757, disrupting the inhibitory effect of mTOR on ULK1 activity and thus contributing to autophagy induction. Pharmacologic treatment and Beclin-1 knockout experimental results establish that, in turn, autophagy enhances SFTSV infection and propagation. Moreover, the minigenome reporter system reveals that SFTSV ribonucleoprotein (the transcription and replication machinery) activity can be bolstered by autophagy. Additionally, we found that the NSs proteins of SFTSV-related bunyaviruses have a conserved function of targeting mTOR. Taken together, we unravel a viral strategy of inducing pro-viral autophagy by interacting with mTOR, sequestering mTOR into IBs and hence provoking the downstream ULK1 pathway, which presents a new paradigm for viral manipulation of autophagy and may help inform future development of specific antiviral therapies against SFTSV and related pathogens.

Clinical evaluation of acute necrotizing encephalopathy in children.

Objective: Acute necrotizing encephalopathy (ANE) is a rare but severe encephalopathy and is associated with a high morbidity and mortality. We aimed to analyze and compare the clinical features and predictive indicators of pediatric ANE. Materials and methods: This retrospective study included children with ANE diagnosed at Guangzhou Women and Children's Medical Center between November 2018 and January 2020. Pediatric patients' information, including clinical characteristics, laboratory tests, neuroelectrophysiology and brain magnetic resonance imaging (MRI) findings, MRI score, brainstem auditory evoked potential (BAEP) grades, ANE severity scores (ANE-SS), and modified Rankin scale (mRS), were collected. Results: Twelve ANE patients were included. Among them, one patient (8.3%) died from brainstem dysfunction, one (8.3%) recovered and 10 (83.3%) experienced neurological sequelae. All patients had an initial viral infection and neurological symptoms such as acute disturbance of consciousness (ADOC) or seizure, and the interval from onset of the disease to neurological manifestations was 3 (1.25-3) days. MRI score-I ranged from 1 to 3 (1.8 ± 0.7), MRI score-II ranged from 1 to 4 (2.5 ± 1.1). ANE-SS varied from 1 to 6 (3.9 ± 1.3). The scores of mRS were from 0 to 6 (2.9 ± 1.7). Higher MRI score were associated with worse outcomes, while the BAEP grade and ANE-SS score were not significantly associated with mRS. Conclusion: ANE is a severe encephalopathy syndrome with rapid progression, resulting in serious neurological sequelae. Compared with BAEP grade and ANE-SS, brain MRI shows more comprehensive advantages in predicting the prognosis of ANE patients. More in-depth research and better indicators are still needed to support the evaluation and treatment of ANE.