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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC 50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8–10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.

Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socioeconomic implications. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiation through the osteogenic pathway during fracture healing has attracted much attention. : The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossification (IO) . The potential functions and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. : In this study, using the tibial monocortical defect model, we observed delayed IO in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiation of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarization by enhancing mitochondrial oxidative phosphorylation. : Our findings revealed a previously unrecognized function of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.

This study examined adolescent basketball participation through the lens of Self-Determination Theory (SDT), focusing on the roles of passion (harmonious and obsessive) and affect (positive and negative), with gender and age as moderators. We collected data from 400 Chinese adolescents from south of China using convenience sampling ( M age = 15.20, SD = 1.99). Participants completed the Passion Scale and Positive and Negative Affect Schedule Scale (PANAS). Basketball participation was operationalized as self-reported engagement in basketball over the past seven days. Hypothesized pathways were tested using structural equation modeling (SEM) in Mplus, which included test of measurement invariance and moderation. Results revealed that harmonious passion positively predicted basketball engagement (β = .280, 95% CI [.127,.432], p = .003) though enhanced positive affect. Specifically, harmonious passion was positively associated with positive affect (β = .495, 95% CI [.356,.635], p < .001), which, in turn, predicted basketball engagement (β = .253, 95% CI [.132,.373], p = .001). In contrast, obsessive passion was linked to negative affect (β = .196, 95% CI [.083,.310], p = .004) but showed no direct effect on basketball participation. While no significant gender differences were observed, age differences emerged. Specifically, the pathways from both harmonious and obsessive passion to basketball engagement were stronger among junior high school students compared to their senior high school counterparts. This study revealed that harmonious passion and positive affect play pivotal roles in sustaining adolescent basketball participation, whereas obsessive passion’s negative emotional consequences may undermine engagement. The findings underscore the importance of interventions designed to promote harmonious passion and positive affect, particularly for senior high students facing academic pressures. Given the cross-sectional design and sampling from southern China, the generalizability of our findings to other cultural contexts or regions of China should be interpreted with caution. Additionally, due to the less-than-ideal model fit in multi-group analyses examining gender as a moderator, results concerning gender differences require the same cautious approach.

Acorus tatarinowii Schott (A. tatarinowii) is a natural medicinal plant. It plays an indispensable role in the treatment of diseases by the empirical medicine system and has achieved remarkable curative effects. A. tatarinowii is often used to treat various diseases, such as depression, epilepsy, fever, dizziness, heartache, stomachache, etc. More than 160 compounds of different structural types have been identified in A. tatarinowii, including phenylpropanoids, terpenoids, lignans, flavonoids, alkaloids, amides, and organic acids. These bioactive ingredients make A. tatarinowii remarkable for its pharmacological effects, including antidepressant, antiepileptic, anticonvulsant, antianxiety, neuroprotective, antifatigue, and antifungal effects, improving Alzheimer’s disease, and so on. It is noteworthy that A. tatarinowii has been widely used in the treatment of brain diseases and nervous system diseases and has achieved satisfactory therapeutic effects. This review focused on the research publications of A. tatarinowii and aimed to summarize the advances in the botany, traditional uses, phytochemistry, and pharmacology, which will provide a reference for further studies and applications of A. tatarinowii.

Background Prediction of the functional outcome for patients with convulsive status epilepticus (CSE) has been a challenge. The aim of this study was to characterize the prognostic factors and functional outcomes of patients after CSE in order to develop a practicable scoring system for outcome prediction. Methods We performed a retrospective explorative analysis on consecutive patients diagnosed with CSE between March, 2008 and November, 2014 in a tertiary academic medical center in northwest China. The modified Rankin Scale (mRS) was used to measure the functional outcome at three months post discharge. Results A total of 132 CSE patients was included, with a median age of 25.5 years and 60.6 % were male. Three months post discharge, an unfavorable outcome with mRS of 3–6 was seen in 62 (47.0 %) patients, 25 (18.9 %) of whom died. Logistic regression analysis revealed that encephalitis ( p  = 0.029), nonconvulsive SE ( p  = 0.018), diazepam resistance ( p  = 0.005), image abnormalities (unilateral lesions, p  = 0.027; bilateral lesions or diffuse cerebral edema, p  < 0.001) and tracheal intubation ( p  = 0.032) were significant independent predictors for unfavorable outcomes. Based on the coefficients in the model, these predictors were assigned a value of 1 point each, with the exception of the image, creating a 6-point scoring system, which we refer to as END-IT, for the outcome prediction of CSE. The area under the receiver operating characteristic curve for the END-IT score was 0.833 and using a cut-off point of 3 produced the highest sum sensitivity (83.9 %) and specificity (68.6 %). Compared with status epilepticus severity score (STESS) and Epidemiology-based Mortality score in SE (EMSE), END-IT score showed better discriminative power and predictive accuracy for the outcome prediction. Conclusions We developed an END-IT score with a strong discriminative power for predicting the functional outcome of CSE patients. External prospective validation in different cohorts is needed for END-IT score.

The weight-adjusted waist index (WWI) has emerged as a reliable indicator of abdominal obesity. α-Klotho, a transmembrane protein, functions as a suppressor of aging. However, the relationship between these two factors remains underexplored. This study aims to investigate the association between WWI and serum α-Klotho levels in middle-aged and elderly Americans, with a focus on exploring the potential mediating role of the systemic immune inflammation index (SII). A cross-sectional study was conducted using data from 6997 middle-aged and elderly Americans participating in the National Health and Nutrition Examination Surveys (NHANES) between 2011 and 2016. Multiple linear regression analysis was employed to assess the relationship between WWI and serum α-Klotho concentrations. Additionally, mediation analysis was performed to investigate the mediating effect of SII on the relationships. Our analysis revealed a significant negative correlation between WWI and serum α-Klotho levels in the survey-weighted multiple linear regression models (adjusted percent change: -7.79; 95% CI: -10.15, -5.37). Mediation analysis demonstrated that the association between WWI and α-Klotho levels was partially mediated by SII (adjusted percent change: -0.88; 95% CI: -1.24, -0.45), with the proportion of mediation amounting to 11.6%. Further age-stratified results showed that the mediating role of SII was more pronounced among individuals aged ≥ 60 years, exhibiting a mediating effect of 26.3%, in contrast to 4.2% for those < 60 years. The findings suggest that WWI is inversely associated with serum α-Klotho concentrations and that this association is partially mediated by SII, especially in older people.

For the past twenty years, chemokines have emerged as a family of critical mediators of cell migration during immune surveillance, development, inflammation and cancer progression. Chemokines bind to seven transmembrane G protein-coupled receptors (GPCRs) that are expressed by a wide variety of cell types and cause conformational changes in trimeric G proteins that trigger the intracellular signaling pathways necessary for cell movement and activation. Although chemokines have evolved to benefit the host, inappropriate regulation or utilization of these small proteins may contribute to or even cause diseases. Therefore, understanding the role of chemokines and their GPCRs in the complex physiological and diseased microenvironment is important for the identification of novel therapeutic targets. This review introduces the functional array and signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as their roles in homeostasis, inflammation, immune responses and cancer.

A bstract This study explores a minimal renormalizable dark matter (DM) model, incorporating a sub-GeV Majorana DM and a singlet scalar particle ϕ . Using scalar and pseudo-scalar interactions (couplings c s and c p ), we investigate implications for DM detection, considering s -wave, p -wave, and combined ( s + p wave) contributions in DM annihilation cross-section, as well as loop-correction contributions to DM-nucleon elastic scattering. Identifying a broad parameter space (10 MeV < m χ ≲ m ϕ ) within the 2 σ allowed region, we explore scenarios (| c s | ≫ | c p |, | c s | ≪ | c p |, and | c s | ≈ | c p |). We find that (i) a non-zero pseudo-scalar coupling alleviates direct detection constraints as a comparison with the previous pure scalar coupling case; (ii) CMB observations set stringent limits on pseudo-scalar interaction dominant cases, making s -wave annihilation viable only for m χ > 1 GeV; (iii) the preferred ϕ -resonance region can be tested in the future indirect detection experiments, such as e-ASTROGAM.

Alkali metals (lithium, sodium, and potassium) are promising as anodes in emerging rechargeable batteries, ascribed to their high capacity or abundance. Two commonly experienced issues, however, have hindered them from commercialization: the dendritic growth of alkali metals during plating and the formation of solid electrolyte interphase due to contact with liquid electrolytes. Many technical strategies have been developed for addressing these two issues in the past decades. Among them, atomic and molecular layer deposition (ALD and MLD) have been drawing more and more efforts, owing to a series of their unique capabilities. ALD and MLD enable a variety of inorganic, organic, and even inorganic-organic hybrid materials, featuring accurate nanoscale controllability, low process temperature, and extremely uniform and conformal coverage. Consequently, ALD and MLD have paved a novel route for tackling the issues of alkali metal anodes. In this review, we have made a thorough survey on surface coatings via ALD and MLD, and comparatively analyzed their effects on improving the safety and stability of alkali metal anodes. We expect that this article will help boost more efforts in exploring advanced surface coatings via ALD and MLD to successfully mitigate the issues of alkali metal anodes.

Empty large volume parenteral (LVP) bottle has irregular shape and narrow opening, and its detection accuracy of the foreign substances at the bottom is higher than that of ordinary packaging bottles. The current traditional detection method for the bottom of LVP bottles is to directly use manual visual inspection, which involves high labor intensity and is prone to visual fatigue and quality fluctuations, resulting in limited applicability for the detection of the bottom of LVP bottles. A geometric constraint-based detection model (GCBDM) has been proposed, which combines the imaging model and the shape characteristics of the bottle to construct a constraint model of the imaging parameters, according to the detection accuracy and the field of view. Then, the imaging model is designed and optimized for the detection. Further, the generalized GCBDM has been adopted to different bottle bottom detection scenarios, such as cough syrup and capsule medicine bottles by changing the target parameters of the model. The GCBDM, on the one hand, can avoid the information at the bottom being blocked by the narrow opening in the imaging optical path. On the other hand, by calculating the maximum position deviation between the center of visual inspection and the center of the bottom, it can provide the basis for the accuracy design of the transmission mechanism in the inspection, thus further ensuring the stability of the detection.