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Public health emergency, such as COVID-19 pandemic, generally has severe impacts on mental health in public. One of the often-neglected negative consequences is that the control and prevention measures of COVID-19 in the post-epidemic can pose psychological threats to public mental health. This study aimed to seek the factors and mechanisms to alleviate this mental health threat based on a sample of university students in China. Accordingly, this study proposed an environmental-individual interaction model examining the multiple mediating effects of self-esteem and resilience in the association between social support and anxiety among university students during COVID-19 control phase. A questionnaire containing multiple scales were administered on the sample of 2734 Chinese university students. Results indicated that social support negatively predicted anxiety through the serial mediating effects of self-esteem and resilience sequentially. Our results highlight the impact of social support and the internal factors on relieving anxiety among university students in COVID-19 control phase. Findings suggest that effective psychological intervention tools should be designed and offered to college students to reduce anxiety distress and improve mental health in the post-epidemic era or the similar situations in the future.

Attention is influenced by information about relationships between ourselves and the objects around us. Self-related objects can either facilitate or disrupt task performance, creating a challenge for identifying the precise nature of the influence of self-relatedness on attention. To address this challenge, we measured different components of attention (alertness and orienting) in the presence of self-related objects using a revised attention network task (ANT). In a self-association task, participants first learned colour-person associations and then carried out a colour-person matching task. This was followed by the ANT, in which these coloured boxes associated with self or friend were displayed as peripheral cues; participants had to judge the direction of an arrow flanked by congruent (low-conflict) or incongruent (high-conflict) distractors presented within one coloured box. The results showed faster and more accurate responses to targets appearing within the self-colour than friend-colour cues in the association task. In the ANT, the analysis of alertness revealed that self-related cues facilitated task performance compared with friend-related cues. The analysis of orienting demonstrated that relative to friend cues, self-cues hampered task performance in invalid trials. Critically, the effects of self-cues on both orienting and alertness were observed only in high conflict situations. These results indicated that self-related objects are powerful cues that enhance attention intensity, which either facilitates task performance when the upcoming target falls within their location or disrupts performance when the target falls outside their location. The data suggest that attentional functions can be tuned by self-saliency in high-demand contexts.

Glucocorticoid receptor modulators (GRM) are the first-line treatment for many immune diseases, but unwanted side effects restrict chronic dosing. However, targeted delivery of a GRM payload via an immunology antibody-drug conjugate (iADC) may deliver significant efficacy at doses that do not lead to unwanted side effects. We initiated our α-TNF-GRM ADC project focusing on identifying the optimal payload and a linker that afforded stable attachment to both the payload and antibody, resulting in the identification of the synthetically accessible maleimide-Gly-Ala-Ala linker. DAR 4 purified ADCs were shown to be more efficacious in a mouse contact hypersensitivity model than the parent α-TNF antibody. Analysis of P1NP and corticosterone biomarkers showed there was a sufficient therapeutic window between efficacy and unwanted effects. In a chronic mouse arthritis model, α-TNF-GRM ADCs were more efficacious than both the parent α-TNF mAb and an isotype control bearing the same GRM payload.

We investigated whether sadness empathy influences prosocial lying. The 139 participants were randomly assigned based on gender to 2 groups according to the event that they read about—sadness empathy priming or neutral—and they then completed a deception game and 2 empathy scales. The results showed that participants' prosocial lying frequency was higher in the sadness empathy-priming condition than the neutral event condition. The perspective-taking component of trait empathy moderated the event's main effect; however, there were no significant gender differences in prosocial lying frequency, and both men and women who experienced another's sadness told prosocial lies to show benevolence. The facilitating effect emerged only in those who had a greater ability to take another person's perspective. The findings indicate that people with sadness empathy, especially those with a strong perspective-taking ability, express their kindness by means of prosocial lying when they communicate with a sad person.

Sounds deviating from an otherwise repetitive background in some task-irrelevant respect (deviant sounds among standard sounds) capture attention in an obligatory fashion and result in behavioral distraction in an ongoing task. Traditionally, such distraction has been considered as the ineluctable consequence of the deviant sound’s low probability of occurrence relative to that of the standard. Recent evidence from a cross-modal oddball task challenged this idea by showing that deviant sounds only yield distraction in a visual task when auditory distractors (standards and deviants) announce with certainty the imminent presentation of a target stimulus (event information), regardless of whether they predict the target’s temporal onset (temporal information). The present study sought to test for the first time whether this finding may be generalized to a purely auditory oddball task in which distractor and target information form part of the same perceptual stimulus. Participants were asked to judge whether a sound starting from a central location moved left or right while ignoring rare and unpredictable changes in the sound’s identity. By manipulating the temporal and probabilistic relationship between sound onset and movement onset, we disentangled the roles of event and temporal information and found that, as in the auditory-visual oddball task, deviance distraction is mediated by the extent to which distractor information harbingers the presentation of the target information (event information). This finding suggests that the provision of event information by auditory distractors is a fundamental prerequisite of behavioral deviance distraction.

We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC50 values as low as 19 nM and moderate selectivity against a kinase panel. Compounds 15, 31a, and 31b inhibit TNFα production in peripheral human monocytes.

A novel series of aminotriazole-based P2X(7) antagonists was synthesized, and their structure-activity relationships (SAR) were investigated for activity at both human and rat P2X(7) receptors. Most compounds showed greater potency at the human receptor although several analogs were discovered with potent activity (pIC(50) > or = 7.5) at both human and rat P2X(7).

We have identified the pyrazolo[3,4-d]pyrimidine A-420983 (compound 7) as a potent inhibitor of lck. A-420983 exhibits oral efficacy in animal models of delayed-type hypersensitivity and organ transplant rejection.

A series of para-substituted 3-phenyl pyrazolopyrimidines was synthesized and evaluated as inhibitors of lck. The nature of the substitution affected enzyme selectivity and potency for lck, src, kdr, and tie-2. The para-phenoxyphenyl analogue 2 is an orally active lck inhibitor with a bioavailability of 69% and exhibits an extended duration of action in animal models of T cell inhibition.

A nucleophilic synthon, (S)-(+)-4-(2-oxazolidonyl)-methyltriphenylphosphinyl iodide 6, available from l-serine in five steps (overall yield of 52%), reacts with aldehydes to produce alkenes in good to excellent yields (74−89%) and, in some cases, provides excellent stereocontrol of the new double bond. The geometry of the newly formed double bond is influenced by the nature of the aldehyde and reaction conditions. The trends in olefin configuration are discussed. Application of this methodology allows for easy preparation of molecules containing double bonds allylic to nitrogen, including oxazolidinones and β,γ-unsaturated amino alcohols. Several of the unsaturated oxazolidinones are converted to β,γ-unsaturated amino alcohols in high yields (75 to 90%).

Sounds deviating from an otherwise repetitive background in some task-irrelevant respect (deviant sounds among standard sounds) capture attention in an obligatory fashion and result in behavioral distraction in an ongoing task. Traditionally, such distraction has been considered as the ineluctable consequence of the deviant sound's low probability of occurrence relative to that of the standard. Recent evidence from a cross-modal oddball task challenged this idea by showing that deviant sounds only yield distraction in a visual task when auditory distractors (standards and deviants) announce with certainty the imminent presentation of a target stimulus (event information), regardless of whether they predict the target's temporal onset (temporal information). The present study sought to test for the first time whether this finding may be generalized to a purely auditory oddball task in which distractor and target information form part of the same perceptual stimulus. Participants were asked to judge whether a sound starting from a central location moved left or right while ignoring rare and unpredictable changes in the sound's identity. By manipulating the temporal and probabilistic relationship between sound onset and movement onset, we disentangled the roles of event and temporal information and found that, as in the auditory-visual oddball task, deviance distraction is mediated by the extent to which distractor information harbingers the presentation of the target information (event information). This finding suggests that the provision of event information by auditory distractors is a fundamental prerequisite of behavioral deviance distraction.

A nucleophilic synthon, (S)-(+)-4-(2-oxazolidonyl)-methyltriphenylphosphinyl iodide 6, available from l-serine in five steps (overall yield of 52%), reacts with aldehydes to produce alkenes in good to excellent yields (74−89%) and, in some cases, provides excellent stereocontrol of the new double bond. The geometry of the newly formed double bond is influenced by the nature of the aldehyde and reaction conditions. The trends in olefin configuration are discussed. Application of this methodology allows for easy preparation of molecules containing double bonds allylic to nitrogen, including oxazolidinones and β,γ-unsaturated amino alcohols. Several of the unsaturated oxazolidinones are converted to β,γ-unsaturated amino alcohols in high yields (75 to 90%).

A series of para-substituted 3-phenyl pyrazolopyrimidines was synthesized and evaluated as inhibitors of lck. The nature of the substitution affected enzyme selectivity and potency for lck, src, kdr, and tie-2. The para-phenoxyphenyl analogue 2 is an orally active lck inhibitor with a bioavailability of 69% and exhibits an extended duration of action in animal models of T cell inhibition.

Chiral allyl amines with the carboncarbon double bond at an internal position undergo regio- and stereocontrolled hydroborations to provide 1,2-amino alcohols in good yields. The precursor olefins are readily available from a nucleophilic alaninol synthon prepared from serine.

MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site. Use of these tools in the optimization of a potent and selective inhibitor lead series is described in the accompanying Letter.

Asparagine (Asn) deamidation is a major source of antibody instability and micro heterogeneity. For this reason, it is critical to accurately characterize both the levels and the sites of Asn deamidation in therapeutic antibodies. Asn deamidation is normally quantified by analyzing antibodies at the peptide level by liquid chromatography-mass spectrometry. This requires denaturation, reduction, alkylation, and enzyme digestion of the antibody prior to analysis. These steps in sample preparation may directly contribute to the total levels of Asn deamidation detected. Therefore, to obtain accurate levels and sites of Asn deamidation, it is important to determine if any deamidation occurred during the sample preparation steps. However, this could be challenging because deamidation that occurred prior to and during sample preparation resulted in peptides with the same retention times and the same molecular weight increase of 1 Da. Sample preparation was carried out in (18)O-water in the current study to differentiate between the two events of Asn deamidation. Using this method, deamidation that occurred during sample preparation resulted in a molecular weight increase of 3 Da instead of 1 Da. This molecular weight difference was readily detected by inspection of the isotopic peak cluster of the peptides containing the deamidation products, isoAsp and Asp residues. It enabled discrimination of deamidation that was due to analytical artifacts and thus determination of the level of deamidation that was present in the samples.

A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 microM) in this latter assay and demonstrates moderate clearance in-vivo.

We describe the identification, SAR, and in vivo pharmacology of a new series of Src-family selective Lck inhibitors. These thienopyridines were designed based on a desire to access the unique residues in the extended hinge region of Lck.

We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.

Optically pure β-aminopiperidines can be prepared in high yields though a thermolytic annulation sequence involving ring opening of an oxazolidinone

Optically pure β-aminopiperidines can be prepared in high yields though a thermolytic annulation sequence involving ring opening of an oxazolidinone

This paper proved that high Tc Ba-T-Cu-O compound have “hole” conductivity property like P-type semiconductor by hot probe measuring. We suposed that high Tc Ba-Y-Cu-O compound is “hole pair” conductivity in superconductivity state.