The qualitative analysis of characteristic of callers to a psychological hotline at the early stage of COVID-19 in China.

BACKGROUND: As the outbreak of COVID-19, traditional face-to-face psychological intervention are difficult to achieve, so hotline becomes available and recommended strategies. The callers' characteristic could help us to study their experiences of emotional distress, as well as the reasons for calling during the pandemic, which can be used to inform future service design and delivery. METHODS: The information of 1558 callers called our hospital' s hotline for help from February 3, 2020, to March 16, 2020 were collected in the form of Tick-box and Free text, and the inductive content analysis was undertaken focusing on the reasons for caller engagement. RESULTS: It was indicated that more than half of the callers are female (59.7%), mostly between the age of 18-59 (76.5%). The average age was 37.13 ± 13.76 years old. The average duration of a call to the hotline was 10.03 ± 9.84 min. The most frequent description emotional state were anxious (45.1%) and calm (30.3%), with the sub-sequence of scared (18.2%), sad (11.9%), and angry (6.9%). All callers displayed a wide range of reasons for calling, with needing support around their emotion (64.6%), seeking practical help (44.0%), and sleep problems (20.3%) constituting the majority of calls. Among the subthemes, 314 callers thought the epidemic has made them upset, 198 asked questions about the epidemic, and 119 reported their life routines were disrupted. The prevalence of key reasons does not appear to differ over time. Through their feedback, 79.1% agreed that they felt emotionally better after calling, and 95.0% agreed that hotline had helped them. CONCLUSIONS: During the epidemic, the most concern of the public is still related to epidemics and its adverse effects. Fortunately, the hotline can be an active and effective rescue measure after an emergency happened.

Design, synthesis, and biological activity evaluation of a series of pleuromutilin derivatives with novel C14 side chains.

In this work, according to the 'me-too me-better' design strategy, a peculiar side chain different from lefamulin at C14 position of pleuromutilin was introduced. A series of novel thioether pleuromutilin derivatives containing cyclohexane in the C14 chain was synthesized by ten-step synthesis reaction. All derivatives were characterized by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometer (HRMS). Furthermore, majority of derivatives displayed moderate antibacterial activity in vitro. However, the compound 2C and 2J exhibited comparable or superior antibacterial activity to lefamulin. The summarized structure-activity relationship not only made the variety of pleuromutilin derivatives more diverse, but also provided new ideas for its design and development.

Design, synthesis and biological evaluation of novel HIV-1 protease inhibitors with pentacyclic triterpenoids as P2-ligands.

The design, synthesis and SAR study of a new series of HIV-1 protease inhibitors with pentacyclic triterpenoids as P2 ligands and phenylsulfonamide as P2' ligands were discussed. These compounds exhibited micromolar inhibitory potency, among which compound T1c displayed HIV-1 protease inhibition with IC50 values of 0.12 µM, which was 67 times the inhibitory activity of its raw material Ursolic acid (8.0 µM).

Antibacterial Activity and Structure-Activity Relationship of a Series of Newly Synthesized Pleuromutilin Derivatives.

A series of novel thioether or sulfoxide-type pleuromutilin derivatives containing heteroaromatic substituents at the end of C14 side chain were designed and synthesized. All of the derivatives were evaluated for their in vitro antibacterial activity. Some of them showed good to excellent antibacterial activity comparable to retapamulin and azamulin in most of the tested Gram-positive pathogens. In this work, a five-membered heterocyclic moiety, a pyrimidine-heterocyclic moiety, or a benzoheterocyclic moiety was introduced in the C14 side chain to increase the structural diversity of the pleuromutilin derivatives. The antibacterial results reveal that the thioether-containing pleuromutilin derivatives exert a more potency activity than the sulfoxide-type derivatives against Gram-positive pathogens. The structure-activity relationship summarized in this work may provide with some interesting clues as to which functionalities are beneficial for high antimicrobial activity of the pleuromutilin derivatives.

Emotion-dependent language featuring depression.

BACKGROUND AND OBJECTIVES: Understanding language features of depression contributes to the detection of the disorder. Considering that depression is characterized by dysfunctions in emotion and individuals with depression often show emotion-dependent cognition, the present study investigated the speech features and word use of emotion-dependent narrations in patients with depression. METHODS: Forty depression patients and forty controls were required to narrate self-relevant memories under five basic human emotions (i.e., sad, angry, fearful, neutral, and happy). Recorded speech and transcribed texts were analyzed. RESULTS: Patients with depression, as compared to non-depressed individuals, talked slower and less. They also performed differently in using negative emotion, work, family, sex, biology, health, and assent words regardless of emotion manipulation. Moreover, the use of words such as first person singular pronoun, past tense, causation, achievement, family, death, psychology, impersonal pronoun, quantifier and preposition words displayed emotion-dependent differences between groups. With the involvement of emotion, linguistic indicators associated with depressive symptoms were identified and explained 71.6% variances of depression severity. LIMITATIONS: Word use was analyzed based on the dictionary which does not cover all the words spoken in the memory task, resulting in text data loss. Besides, a relatively small number of depression patients were included in the present study and therefore the results need confirmation in future research using big emotion-dependent data of speech and texts. CONCLUSIONS: Our findings suggest that consideration of different emotional contexts is an effective means to improve the accuracy of depression detection via the analysis of word use and speech features.

The effects of family environment cognition and its difference perceived by adolescents and their parents on the treatment effect of non-suicidal self-injury behaviors in adolescents: a 1-year prospective cohort study.

Introduction: Family environment is the primary environment for adolescent growth and development, which is believed to have an important impact on the occurrence of non-suicidal self-injury (NSSI) behavior in adolescents. This study aimed to explore the effects of family environment cognition and cognitive differences perceived by adolescents and their parents on the treatment effects of NSSI in adolescents and to provide more potential perspectives for NSSI treatment. Methods: A one-year prospective longitudinal sub-cohort investigation was carried out among 199 adolescents engaged in NSSI and one of their important guardians from the Longitudinal Psychosomatic Disease Study (LoPDS). The NSSI behaviors of adolescents were evaluated at 3 months, 6 months and 1 year after enrollment. The family environment scale (FES) and NSSI Behavior Questionnaire were used as assessment tools for family environment and adolescents NSSI behaviors. Multiple linear regression was used to investigate the role of family environment perception difference in the treatment effect of adolescent NSSI. Results: After one year of follow-up, the perceived self-injury impulse score in recent 2 weeks, self-injury impulse frequency in recent 2 weeks, total number of self-injury in recent 2 weeks decreased significantly. The higher the adolescent family cohesion (Beta: 1.130, 95% CI: 0.886,1.373; p=0.032), parental family expressiveness (Beta: 0.818, 95% CI: 0.375,1.260; p=0.037) and parental family active-recreational orientation score (Beta: 0.609, 95% CI: 0.236,0.981; p=0.048), the better the treatment effect. However, higher adolescent family conflict (Beta: -0.838, 95% CI: -1.377,-0.298; p=0.024) were associated with lower treatment outcomes. The greater the cognitive difference between parents and adolescents in family cohesion (Beta: -1.307, 95% CI: -2.074,-0.539; p=0.014) and family conflict(Beta: -0.665, 95% CI: -0.919,-0.410; p=0.037), the worse the therapeutic effect of NSSI might be. Discussion: There were certain differences in the cognition of family relationships between parents and adolescents, and subjective family relationship cognition and cognitive differences had a significant effect on the treatment effect of NSSI in adolescents. Helping them identify the cause of cognitive differences and conducting systematic family therapy from the points of difference may be another perspective to improve the treatment effect of NSSI in adolescents.

Mental health status of healthcare workers assisted in Hubei during the initial outbreak of COVID-19 and their influencing factors: a prospective cohort study.

OBJECTIVES: The COVID-19 outbreak beginning in late 2019 has resulted in negative emotions among the public. However, many healthcare workers risked their lives by voluntarily travelling to the worst-hit area, Hubei Province, to support antipandemic work. This study explored the mental health changes in these healthcare workers and tried to discover the influencing factors. DESIGN: A longitudinal online survey was begun on 8 February 2020, using the snowball sampling method, and this first phase ended on 22 February 2020 (T1). The follow-up survey was conducted from 8 February to 22 February 2021 (T2). SETTING: Healthcare workers from outside of the Hubei area who went to the province to provide medical assistance. PARTICIPANTS: 963 healthcare workers who completed both surveys. MEASURES: Self-Rating Scale of Sleep (SRSS), Generalised Anxiety Scale (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9). RESULTS: There were no significant differences in the SRSS scores or in the GAD-7 scores between T1 and T2 (t=0.994, 0.288; p>0.05). However, the PHQ-9 score at T2 was significantly higher than the score at T1 (t=-10.812, p<0.001). Through multiple linear regression analysis, we found that the following traits could predict higher GAD-7 and PHQ-9 scores at T2: male sex, single marital status, occupation of nurse, lower professional technical titles, healthcare workers having a history of psychosis, treating seriously ill patients, having relatively poor self-perceived health, caring for patients who died and having family members who had been infected with COVID-19. CONCLUSIONS: The results indicate that the depression levels of these special healthcare workers increased in the long term, and the initial demographics and experiences related to the pandemic played an important role in predicting their long-term poor mental health. In the future, more appropriate psychological decompression training should be provided for these special healthcare workers.

Altered centromedial amygdala functional connectivity in adults is associated with childhood emotional abuse and predicts levels of depression and anxiety.

BACKGROUND: Childhood maltreatment is significantly associated with greater occurrence of mental disorders in adulthood such as depression and anxiety. As a key node of the limbic system, the amygdala is engaged in emotional processing and regulation and is dysfunctional in many psychiatric disorders. The present study aimed at exploring the association between childhood maltreatment and amygdala-based functional networks and their potential contributions to depression and anxiety. METHODS: Totally 90 Chinese healthy volunteers participated in a resting-state fMRI experiment. Levels of childhood maltreatment experience were assessed using the Childhood Trauma Questionnaire (CTQ-SF) as well as levels of depression and anxiety. Associations between CTQ-SF scores and bilateral amygdala gray matter volume and resting-state functional connectivity (RSFC) of the amygdala and selected regions of interest were analyzed using multiple regression analyses with sex and age as covariates. A subsequent moderation analysis was performed to identify whether associations were predictive of depression and anxiety levels. RESULTS: Childhood maltreatment was significantly negatively associated with RSFC between left amygdala and anterior insula. Further sub-region analyses revealed that this negative association only occurred for the left centromedial amygdala subregion, which subsequently moderated the relationship between levels of childhood emotional abuse and depression / anxiety. LIMITATIONS: No psychiatric patients were involved and specific neural associations with different childhood maltreatment subtypes need to be examined in future studies. CONCLUSION: The present findings provide evidence for altered RSFC of centromedial amygdala and the anterior insula associated with childhood maltreatment and which moderate levels of depression and anxiety in adulthood.

Disorder-specific impaired neurocognitive function in major depression and generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are both highly prevalent and comorbid psychiatric disorders. Neurocognitive dysfunction has been commonly found in MDD, but the findings in GAD are inconsistent. Few studies have directly compared cognitive performance between GAD and MDD. Therefore, the present study aimed to reveal the similar and distinct cognitive impairments between both disorders. METHODS: Three non-overlapping and non-comorbid groups were enrolled in the current study including patients with GAD (n = 37), MDD (n = 107) and healthy controls (n = 74). Levels of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD) respectively. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to compare the cognitive performance, including sustained attention, visual memory, executive functions and learning. RESULTS: Both MDD and GAD groups demonstrated common significant deficits in sustained attention, visual memory, working memory and learning when compared to healthy controls. Despite the similarities, the MDD group had significantly greater impairment in learning, particularly generalization, while the GAD group demonstrated more pronounced deficits in visual memory. LIMITATIONS: Patients involved were medicated and the sample size for GAD was relatively small. CONCLUSIONS: The significant differences in visual memory and learning between MDD and GAD groups might be indicators to distinguishing both disorders. These results confirm that cognitive function is of great importance as a future target for treatment in order to improve wellbeing, quality of life and functionality in both GAD and MDD.

Longitudinal study of mental health changes in residents affected by an initial outbreak of COVID-19 in China.

Introduction: The COVID-19 pandemic is ongoing, and the world continues to work to defeat it. We designed this study to understand the longitudinal change in the mental health of residents who experienced the initial disease outbreak in China and to explore the long-term influencing factors. Methods: The Perceived Stress Scale (PSS), Generalized Anxiety Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were administered to the same sample four times: during the initial outbreak (T1), 1 month later (T2), 18 months later (T3), and 26 months later (T4). Results: A total of 397 participants completed all of the follow ups. The mean PSS scores among the four time points showed significant differences (F = 183.98, P < 0.001), with the highest score at T1 (15.35 ± 7.14), a sharp decline at T2 (11.27 ± 6.27), an obvious rebound at T3 (15.17 ± 7.46), and finally a slight decrease at T4 (14.41 ± 7.99). Among the four mean GAD-7 scores, significant differences were also found (F = 242.0, P < 0.001), with the trend that from T1 (7.42 ± 6.03) to T2 (7.35 ± 5.88), the scores remained steady, while they showed an apparent decline at T3 (5.00 ± 5.30) and no obvious change at T4 (4.91 ± 4.81). There were no significant differences among the mean PHQ-9 scores (F = 1.256, P < 0.284). The long-term influencing factors differed for stress, anxiety and depression, but all three were influenced by a history of psychosis at T4, quarantine status and whether the participants' family members were infected during the initial outbreak. Discussion: The survey revealed that repeated outbreaks in other areas also had an impact on those who experienced the initial outbreak, with a return of stress, a decline in anxiety, and no change in depression, which provides direction for interventions in the future.

Psychosocial Factors Associated With Increased Adolescent Non-suicidal Self-Injury During the COVID-19 Pandemic.

Non-suicidal self-injury (NSSI) in adolescents hospitalized with psychiatric disorders continues to increase after the outbreak of COVID-19. This study aimed to explore the relationship between the pandemic and NSSI among adolescents and whether the composition of psychosocial factors related to NSSI has changed during the pandemic. Through the retrospective analysis of medical records retrieved from the electronic system of the psychiatric hospital located in Chengdu from January 2016 to March 2021, 609 medical records of adolescents were obtained. The main potential psychosocial factors were determined by deductive content analysis. Among the 609 adolescents, 420 subjects had engaged in NSSI, while 189 did not. We found that the percentage of adolescents who had engaged in NSSI in 2016 was only 29.2%, reaching 34.5% in 2017, 45.7% in 2018, 61.3% in 2019, 92.5% in 2020, and 95.9% in 2021. In the binary logistic regression model, female sex (OR = 0.073, 95% CI: 0.028-0.186), older age (OR = 1.234, 95% CI: 1.030-1.478), having a single parent (OR = 7.865, 95% CI: 3.997-15.476), having experienced trauma (OR = 2.192, 95% CI: 1.032-4.654), having experienced social isolation from peers (OR = 8.139, 95% CI: 4.037-16.408), having experienced body-focused bullying (OR = 3.078, 95% CI: 1.295-7.318), overuse of a mobile phone in the parents' opinions (OR = 4.354, 95% CI: 1.380-13.738), having attempted suicide (OR = 9.120, 95% CI: 4.492-18.512), and during the pandemic (time point is January 30, 2020) (OR = 5.399, 95% CI: 1.679-17.357) were the factors that were significantly associated with NSSI. When comparing the differences in psychosocial factors between the pre-pandemic and the during-pandemic groups, the results showed that the family constitution, parent-child relationships, mobile phone overuse, and stressful learning were important factors. Tailored interventions geared towards changed psychosocial factors should be formulated.

Structure-function analysis of Escherichia coli MnmG (GidA), a highly conserved tRNA-modifying enzyme.

The MnmE-MnmG complex is involved in tRNA modification. We have determined the crystal structure of Escherichia coli MnmG at 2.4-A resolution, mutated highly conserved residues with putative roles in flavin adenine dinucleotide (FAD) or tRNA binding and MnmE interaction, and analyzed the effects of these mutations in vivo and in vitro. Limited trypsinolysis of MnmG suggests significant conformational changes upon FAD binding.

The structure of the exopolyphosphatase (PPX) from Escherichia coli O157:H7 suggests a binding mode for long polyphosphate chains.

Polyphosphate (polyP) is a linear polymer consisting of tens to hundreds of phosphate molecules joined together by high-energy anhydride bonds. These polymers are found in virtually all prokaryotic and eukaryotic cells and perform many functions; prominent among them are the responses to many stresses. Polyphosphate is synthesized by polyP kinase (PPK), using the terminal phosphate of ATP as the substrate, and degraded to inorganic phosphate by both endo- and exopolyphosphatases. Here we report the crystal structure and analysis of the polyphosphate phosphatase PPX from Escherichia coli O157:H7 refined at 2.2 Angstroms resolution. PPX is made of four domains. Domains I and II display structural similarity with one another and share the ribonuclease-H-like fold. Domain III bears structural similarity to the N-terminal, HD domain of SpoT. Domain IV, the smallest domain, has structural counterparts in cold-shock associated RNA-binding proteins but is of unknown function in PPX. The putative PPX active site is located at the interface between domains I and II. In the crystal structure of PPX these two domains are close together and represent the "closed" state. Comparison with the crystal structure of PPX/GPPA from Aquifex aeolicus reveals close structural similarity between domains I and II of the two enzymes, with the PPX/GPPA representing an "open" state. A striking feature of the dimer is a deep S-shaped canyon extending along the dimer interface and lined with positively charged residues. The active site region opens to this canyon. We postulate that this is a likely site of polyP binding.

The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot.

In Escherichia coli, RlmB catalyzes the methylation of guanosine 2251, a modification conserved in the peptidyltransferase domain of 23S rRNA. The crystal structure of this 2'O-methyltransferase has been determined at 2.5 A resolution. RlmB consists of an N-terminal domain connected by a flexible extended linker to a catalytic C-terminal domain and forms a dimer in solution. The C-terminal domain displays a divergent methyltransferase fold with a unique knotted region, and lacks the classic AdoMet binding site features. The N-terminal domain is similar to ribosomal proteins L7 and L30, suggesting a role in 23S rRNA recognition. The conserved residues in this novel family of 2'O-methyltransferases cluster in the knotted region, suggesting the location of the catalytic and AdoMet binding sites.

Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution.

Chondroitin Sulfate ABC lyase I from Proteus vulgaris is an endolytic, broad-specificity glycosaminoglycan lyase, which degrades chondroitin, chondroitin-4-sulfate, dermatan sulfate, chondroitin-6-sulfate, and hyaluronan by beta-elimination of 1,4-hexosaminidic bond to unsaturated disaccharides and tetrasaccharides. Its structure revealed three domains. The N-terminal domain has a fold similar to that of carbohydrate-binding domains of xylanases and some lectins, the middle and C-terminal domains are similar to the structures of the two-domain chondroitin lyase AC and bacterial hyaluronidases. Although the middle domain shows a very low level of sequence identity with the catalytic domains of chondroitinase AC and hyaluronidase, the residues implicated in catalysis of the latter enzymes are present in chondroitinase ABC I. The substrate-binding site in chondroitinase ABC I is in a wide-open cleft, consistent with the endolytic action pattern of this enzyme. The tryptophan residues crucial for substrate binding in chondroitinase AC and hyaluronidases are lacking in chondroitinase ABC I. The structure of chondroitinase ABC I provides a framework for probing specific functions of active-site residues for understanding the remarkably broad specificity of this enzyme and perhaps engineering a desired specificity. The electron density map showed clearly that the deposited DNA sequence for residues 495-530 of chondroitin ABC lyase I, the segment containing two putative active-site residues, contains a frame-shift error resulting in an incorrectly translated amino acid sequence.

High-resolution crystal structure of Arthrobacter aurescens chondroitin AC lyase: an enzyme-substrate complex defines the catalytic mechanism.

Chondroitin lyases (EC 4.2.2.4 and EC 4.2.2.5) are glycosaminoglycan-degrading enzymes that act as eliminases. Chondroitin lyase AC from Arthrobacter aurescens (ArthroAC) is known to act on chondroitin 4-sulfate and chondroitin 6-sulfate but not on dermatan sulfate. Like other chondroitin AC lyases, it is capable of cleaving hyaluronan. We have determined the three-dimensional crystal structure of ArthroAC in its native form as well as in complex with its substrates (chondroitin 4-sulfate tetrasaccharide, CS(tetra) and hyaluronan tetrasaccharide) at resolution varying from 1.25 A to 1.9A. The primary sequence of ArthroAC has not been previously determined but it was possible to determine the amino acid sequence of this enzyme from the high-resolution electron density maps and to confirm it by mass spectrometry. The enzyme-substrate complexes were obtained by soaking the substrate into the crystals for varying lengths of time (30 seconds to ten hours) and flash-cooling the crystals. The electron density map for crystals soaked in the substrate for as short as 30 seconds showed the substrate clearly and indicated that the ring of central glucuronic acid assumes a distorted boat conformation. This structure strongly supports the lytic mechanism where Tyr242 acts as a general base that abstracts the proton from the C5 position of glucuronic acid while Asn183 and His233 neutralize the charge on the glucuronate acidic group. Comparison of this structure with that of chondroitinase AC from Flavobacterium heparinum (FlavoAC) provides an explanation for the exolytic and endolytic mode of action of ArthroAC and FlavoAC, respectively.

Crystal structure of a dodecameric FMN-dependent UbiX-like decarboxylase (Pad1) from Escherichia coli O157: H7.

The crystal structure of the flavoprotein Pad1 from Escherichia coli O157:H7 complexed with the cofactor FMN has been determined by the multiple anomalous diffraction method and refined at 2.0 A resolution. This protein is a paralog of UbiX (3-octaprenyl-4-hydroxybenzoate carboxylyase, 51% sequence identity) that catalyzes the third step in ubiquinone biosynthesis and to Saccharomyces cerevisiae Pad1 (54% identity), an enzyme that confers resistance to the antimicrobial compounds phenylacrylic acids through decarboxylation of these compounds. Each Pad1 monomer consists of a typical Rossmann fold containing a non-covalently bound molecule of FMN. The fold of Pad1 is similar to MrsD, an enzyme associated with lantibiotic synthesis; EpiD, a peptidyl-cysteine decarboxylase; and AtHAL3a, the enzyme, which decarboxylates 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine during coenzyme A biosynthesis, all with a similar location of the FMN binding site at the interface between two monomers, yet each having little sequence similarity to one another. All of these proteins associate into oligomers, with a trimer forming the common structural unit in each case. In MrsD and EpiD, which belong to the homo-dodecameric flavin-containing cysteine decarboxylase (HFCD) family, these trimers associate further into dodecamers. Pad1 also forms dodecamers, although the association of the trimers is completely different, resulting in exposure of a different side of the trimer unit to the solvent. This exposure affects the location of the substrate binding site and, specifically, its access to the FMN cofactor. Therefore, Pad1 forms a separate family, distinguishable from the HFCD family.