Search

Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top, facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents. Annotated structural atlas of cytokines and cytokine receptors featuring hotspots in a unified format, help to understand the mechanisms of cytokine-mediated signal transduction pathways and formulate therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. Methods: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. Results: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT,)and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. Conclusion: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease. Topical medicines are the preferred treatment for mild to moderate psoriasis, but the effect of excipients used in semi‐solid preparations on psoriasis‐like skin inflammation is not fully understood. In the present study, we investigated the effect of stearyl alcohol, a commonly used excipient, on imiquimod (IMQ)‐induced psoriasis‐like skin inflammation in mice. Psoriasis‐like skin inflammation was induced by topical IMQ treatment on the back of mice. Skin lesion severity was evaluated by using psoriasis area and severity index (PASI) scores. The skin sections were stained by haematoxylin–eosin and immunohistochemistry. Stearyl alcohol (20% in vaseline) treatment significantly reduced the IMQ‐induced increase of PASI scores and epidermal thickness in mice. IMQ treatment increased the number of Ki67‐ and proliferating cell nuclear antigen (PCNA)‐positive cells in the skin, and the increases were inhibited by stearyl alcohol (20% in vaseline) treatment. Stearyl alcohol treatment (1%, 5%, 10% in vaseline) dose‐dependently ameliorated IMQ‐induced increase of PASI scores and epidermal thickness in mice. Hexadecanol (20% in vaseline), stearic acid (20% in vaseline) and vaseline treatment had no significant effect on IMQ‐induced psoriasis‐like skin inflammation in mice. In conclusion, stearyl alcohol has the effect of improving IMQ‐induced psoriasis‐like skin inflammation in mice. [ABSTRACT FROM AUTHOR]

Viruses are one of the leading causes of human disease, and many highly pathogenic viruses still have no specific treatment drugs. Therefore, producing new antiviral drugs is an urgent matter. In our study, we first found that the natural wasp venom peptide Protopolybia-MP III had a significant inhibitory effect on herpes simplex virus type 1 (HSV-1) replication in vitro by using quantitative real-time PCR (qPCR), Western blotting, and plaque-forming assays. Immunofluorescence analysis showed Protopolybia-MP III could enter cells, and it inhibited multiple stages of the HSV-1 life cycle, including the attachment, entry/fusion, and post-entry stages. Furthermore, ultracentrifugation and electron microscopy detected that Protopolybia-MP III significantly suppressed HSV-1 virion infectivity at different temperatures by destroying the integrity of the HSV-1 virion. Finally, by comparing the antiviral activity of Protopolybia-MP III and its mutants, a series of peptides with better anti-HSV-1 activity were identified. Overall, this work found the function and mechanism of the antiviral wasp venom peptide Protopolybia-MP III and its derivatives against HSV-1 and laid the foundation for the research and development of wasp venom-derived antiviral candidate peptide drugs. [ABSTRACT FROM AUTHOR]

Oncolytic viruses (OVs) are appealing anti-tumor agents. But it is limited in its effectiveness. In this study, we used combination therapy with immune checkpoint inhibitor to enhance the antitumor efficacy of OVs. Using reverse genetics technology, we rescued an oncolytic influenza virus with the name delNS1-GM-CSF from the virus. After identifying the hemagglutination and 50% tissue culture infectivedose (TCID50) of delNS1-GM-CSF, it was purified, and the viral morphology was observed under electron microscopy. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was used to identify the level of GM-CSF expression in delNS1-GM-CSF, and the GM-CSF expression level was determined after infection with delNS1-GM-CSF by enzyme linked immunosorbent assay (ELISA). To study the tumor-killing effect of delNS1-GM-CSF, we utilized the hepatocellular carcinoma (HCC) tumor-bearing mouse model. To examine signaling pathways, we performed transcriptome sequencing on mouse tumor tissue and applied western blotting to confirm the results. Changes in T-cell infiltration in HCC tumors following treatment were analyzed using flow cytometry and immunohistochemistry. DelNS1-GM-CSF can target and kill HCCs without damaging normal hepatocytes. DelNS1-GM-CSF combined with programmed cell death 1 blockade therapy enhanced anti-tumor effects and significantly improved mouse survival. Further, we found that combination therapy had an antitumor impact via the janus kinase-signal transducer and activator of transcription (JAK2-STAT3) pathway as well as activated CD4+ and CD8+T cells. Interestingly, combined therapy also showed promising efficacy in distant tumors. DelNS1-GM-CSF is well targeted. Mechanistic investigation revealed that it functions through the JAK2-STAT3 pathway. Combination immunotherapies expected to be a novel strategy for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Water can significantly enhance the thermal spontaneous combustion and explosion hazard of alpha-aluminum hydride (α-AlH 3). Thermal analysis suggested that, as the water content increased from 10% to 40%, the total reaction heat was increased by 68.3%. α-AlH 3 with different water contents (10%–40%) underwent hydrolysis reaction and oxidation reaction with the activation energy of 57.9–68.7 kJ/mol and 88.3–107.6 kJ/mol, respectively. As the heating rate increased from 0.2 to 2 °C/min, the onset temperature, the peak temperature, and the maximum heat flow of the exothermic reaction were increased. As the storage temperature increased from 45 to 65 °C, the time to maximum reaction rate decreased from 5.16 to 0.84 h. Combining the results of SEM, XRD, XPS and thermal analysis, the reaction mechanism of α-AlH 3 and water under isothermal and non-isothermal conditions was revealed. • The effect of water content on the thermal stability of α-AlH 3 is analyzed. • Isothermal and non-isothermal stability of α-AlH 3 and water are studied. • The reaction mechanism of α-AlH 3 and water is revealed. [ABSTRACT FROM AUTHOR]

Hydrochloric acid (HCl solution) can reduce the thermal stability of alpha-aluminum hydride (α-AlH 3). Thermal analysis suggested that, as the acid content of α-AlH 3 -HCl solution mixtures increased from 0% to 40.4%, the overall reaction heat (ΔH) was increased by 142.3%. The activation energy (E a) of the reaction between α-AlH 3 and the acid was 50.7–58.8 kJ/mol, and that of the oxidation reaction was 98.7–141.8 kJ/mol. The initiation of the reaction between α-AlH 3 and acid required low energy. As the heating rate increased, the onset temperature and the maximum heat flow of the exothermic reactions increased. At constant temperature, the reaction rate increased rapidly and then decreased slowly. As the constant temperature increased from 70 to 85 °C, the time to reach the maximum reaction rate was reduced by 89.9%. Combining with the SEM, XRD, and XPS analysis, the reaction mechanism of α-AlH 3 and hydrochloric acid was revealed in depth. [Display omitted] • The effect of acid content on the thermal stability of α-AlH 3 is analyzed. • Isothermal and non-isothermal stability of α-AlH 3 -HCl(aq) mixtures is studied. • The reaction mechanism of α-AlH 3 and acid is revealed. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the characteristics of dysphagia in stroke patients with different lesion sites and explore the factors that impact the duration of nasogastric tube after post‐stroke dysphagia (PSD). Methods: Patients with PSD were screened for analysis. Stroke types and lesion sites were confirmed using MRI or CT scans. Included patients were categorized into two groups: supratentorial stroke group (including lobar and deep intracerebral stroke subgroups) and infratentorial stroke group (including brainstem and cerebellar stroke subgroups). Fiberoptic endoscopic evaluation of swallowing (FEES), Penetration‐aspiration scale (PAS), Yale pharyngeal residue (PR) severity rating scale, Functional oral intake scale (FOIS), Murray secretion severity rating scale (MSS), laryngopharyngeal sensation, and vocal fold mobility were investigated to assess the swallowing function. Results: A total of 94 patients were included in the final analysis. Significant differences were found in PR scores (p <.001), PAS scores (p <.05), MSS scores (p <.05), and vocal fold mobility (p <.001) between infratentorial and supratentorial stroke groups. Moreover, lobar stroke showed significantly higher PR scores compared to the deep intracerebral stroke group (p <.05). Kaplan–Meier survival analysis indicated significant differences in the duration of nasogastric tube placement among the following groups: infratentorial versus supratentorial stroke, PAS ≤ 5 versus PAS > 5, PR ≥ 3 versus PR < 3, and normal vocal fold mobility versus vocal fold motion impairment group (p <.05). Conclusions: The infratentorial stroke may lead to worse swallowing function as compared to a supratentorial stroke. Additionally, patients with infratentorial stroke, PAS > 5, PR ≥ 3, or vocal fold motion impairment may contribute to a longer duration of nasogastric tube placement. [ABSTRACT FROM AUTHOR]

We report two atomically precise alloy nanoclusters of Ag4Rh2(C≡CArF)8(PPh3)2 and Au4Rh2(C≡CArF)8(PPh3)2 (Ar = 3,5-(CF3)2C6H3, abbreviated as Ag4Rh2 and Au4Rh2, respectively) co-protected by alkynyl and phosphine ligands. Both clusters have identical octahedral metal core configurations and can be termed superatoms with two free electrons. However, they possess different optical features, manifested by totally different absorbance peaks, and drastically different emission peaks, and also, Ag4Rh2 has a much higher fluorescence quantum yield (18.43%) than Au4Rh2 (4.98%). Moreover, Au4Rh2 exhibited markedly superior catalytic performance in the electrochemical hydrogen evolution reaction (HER), manifested by a much lower overpotential at 10 mA cm−2 and better stability. Density functional theory (DFT) calculations revealed that the free energy change of Au4Rh2 for the adsorption of two H* (0.64 eV) is lower than that of Ag4Rh2 for the adsorption of one H* (−0.90 eV) after stripping a single alkynyl ligand from the cluster. In contrast, Ag4Rh2 demonstrated much stronger catalytic capability for catalyzing 4-nitrophenol reduction. The present study provides an exquisite example to understand the structure–property relationship of atomically precise alloy nanoclusters, and emphasizes the importance of fine-tuning of the physicochemical properties and catalytic performance of the metal nanoclusters through modulating the metal core and beyond. [ABSTRACT FROM AUTHOR]

Portulaca oleracea (PO) is a commonly known medicinal crop that is an important ingredient for traditional Chinese medicine (TCM) due to its use as a vegetable in the diet. PO has been recorded to be frequently adulterated by other related species in the market of herbal plants, distorting the PO plant identity. Thus, identification of the botanical origin of PO is a crucial step before pharmaceutical or functional food application. In this research, a quick assay named "loop-mediated isothermal amplification (LAMP)" was built for the specific and sensitive authentication of PO DNA. On the basis of the divergences in the internal transcribed spacer 2 (ITS2) sequence between PO and its adulterant species, the LAMP primers were designed and verified their specificity, sensitivity, and application for the PO DNA authentication. The detection limit of the LAMP assay for PO DNA identification specifically was 100 fg under isothermal conditions at 63 °C for 30 min. In addition, different heat-processed PO samples can be applied for use in PO authentication in the LAMP assay. These samples of PO were more susceptible to the effect of steaming in authentication by PCR than boiling and drying treatment. Furthermore, commercial PO samples pursued from herbal markets were used to display their applicability of the developed LAMP analysis for PO postharvest authentication, and the investigation found that approximately 68.4% of PO specimens in the marketplace of herbal remedies were adulterated. In summary, the specific, sensitive, and rapid LAMP assay for PO authentication was first successfully developed herein, and its practical application for the inspection of adulteration in PO samples from the herbal market was shown. This LAMP assay created in this study will be useful to authenticate the botanical origin of PO and its commercial products. [ABSTRACT FROM AUTHOR]

Bimetallic Palladium‐based catalysts as an alternative of Pt‐free electrocatalysts play a vital role in electrocatalysis. The doping of transition metal (M) into the ultrathin Pd nanosheets is new promising strategy to regulate the reactivity and durability of surface Pd sites. In this work, an in‐depth investigation of the origin oxygen reduction reaction (ORR) activity and stability over 2D ultrathin PdM bimetallenes is presented. The M doping can greatly modify the reactivity of the Pd site by changing the local Fermi softness (SF(r)). All PdM bimetallenes follow the dissociative 4e− pathway, and a thorough screening identified several promising alternatives (PdTa, PdHf, PdZr, and PdNb) with much lower ORR overpotential than the pure Pd(111) metallene. The Pd–O bond length and the Fermi softness of surface Pd atoms are effective descriptors of the adsorption of O* key intermediates. The hetero‐metal induced ligand effect plays the key role for the activity improvement, which modifies the electronic properties and surface reactivity of Pd by the Pd−M orbital hybridization and result in the decline of bonding filling between Pd 3dz2 and O* 2p orbital. The computational insight provides useful guideline for future experimental realizations of bimetallic Pd‐based nanoalloys in ORR and other electrocatalytic reactions. [ABSTRACT FROM AUTHOR]

Pathogens co-evolved with ticks to facilitate blood collection and pathogen transmission. Although tick saliva was recently found to be rich in bioactive peptides, it is still elusive which saliva peptide promotes virus transmission and which pathways are invovled. Here, we used a saliva peptide HIDfsin2 and a severe fever with thrombocytopenia syndrome virus (SFTSV) both carried by the tick Haemaphysalis longicornis to elucidate the relationship between tick saliva components and tick-borne viruses. HIDfsin2 was found to promote the replication of SFTSV in a dose-dependent manner in vitro. HIDfsin2 was further revealed to MKK3/6-dependently magnify the activation of p38 MAPK. The overexpression, knockdown and phosphorylation site mutation of p38α indicated that p38 MAPK activation facilitated SFTSV infection in A549 cells. Moreover, the blockade of p38 MAPK activation significantly suppressed SFTSV replication. Differently, HIDfsin2 or pharmacological inhibition of p38 MAPK activation had no effect on a mosquito-borne Zika virus (ZIKV). All these results showed that HIDfsin2 specifically promoted SFTSV replication through the MKK3/6-dependent enhancement of p38 MAPK activation. Our study provides a new perspective on the transmission of tick-borne viruses under natural conditions, and supports that the blockade of p38 MAPK activation can be a promising strategy against the mortal tick-borne virus SFTSV. [ABSTRACT FROM AUTHOR]

To prevent the spread of the COVID-19 epidemic on campus, universities in outbreak areas in China can implement closed-loop management. Objects: This study aimed to explore the relationship between mindfulness and mental health of college students under closed-loop management. Measures: 11,939 college students from a university in Changsha, China participated in the online survey during the closed-loop management period. The Chinese version of Perceived Stress Scale, the Emotion Regulation Questionnaire-Cognitive Reappraisal, the Mindful Attention Awareness Scale, the 7-item General Anxiety Disorder questionnaire, and the 9-item Patient Health Questionnaire were administered to the college students. Results: We found that mindfulness was negative association with mental health during the closed-loop management period. Perceived stress mediated the relationship between mindfulness and mental health. Cognitive reappraisal moderated the relationship between mindfulness and perceived stress. Specifically, when the level of mindfulness is the same, individuals with more cognitive reappraisal tend to experience a less perceived stress. Conclusion: The results of this study are of great significance to improve the mental health of college students during closed-loop management period. • Research conducted during closed-loop management period in universities • A large sample of 11,542 college students • Anxiety and depression levels were higher during the closed-loop management period. • The mediating role of perceived stress between mindfulness and mental health • The moderating role of cognitive reappraisal between mindfulness and perceived stress [ABSTRACT FROM AUTHOR]

Topological Data Analysis (TDA) is an approach to analyzing the shape of data using techniques from algebraic topology. The staple of TDA is Persistent Homology (PH). Recent years have seen a trend of combining PH and Graph Neural Networks (GNNs) in an end-to-end manner to capture topological features from graph data. Though effective, these methods are limited by the shortcomings of PH: incomplete topological information and irregular output format. Extended Persistent Homology (EPH), as a variant of PH, addresses these problems elegantly. In this paper, we propose a plug-in topological layer for GNNs, termed Topological Representation with Extended Persistent Homology (TREPH). Taking advantage of the uniformity of EPH, a novel aggregation mechanism is designed to collate topological features of different dimensions to the local positions determining their living processes. The proposed layer is provably differentiable and more expressive than PH-based representations, which in turn is strictly stronger than message-passing GNNs in expressive power. Experiments on real-world graph classification tasks demonstrate the competitiveness of TREPH compared with the state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper, we investigated the early-castrated Holstein cattle liver transcriptome and metabolome and conducted a comprehensive analysis of two omics associated with the IMF deposition using transcriptomics and untargeted metabolomics under different treatments: non−castrated and slaughtered at 16 months of age (GL16), castrated at birth and slaughtered at 16 months of age (YL16), and slaughtered at 26 months of age (YL26).The results demonstrated that implementation of early castration modified the hepatic metabolites and the related biological pathways by regulating the relevant gene expression, which could represent a better rearing method for the production of high-marbled and healthier beef products. The intramuscular fat (IMF), or so-called marbling, is known as potential determinant of the high quality beef in China, Korea, and Japan. Of the methods that affect IMF content in cattle, castration is markedly regarded as an effective and economical way to improve the deposition of IMF but with little attention to its multi-omics in early-castrated cattle. The aim of this study was to investigate the liver transcriptome and metabolome of early-castrated Holstein cattle and conduct a comprehensive analysis of two omics associated with the IMF deposition using transcriptomics and untargeted metabolomics under different treatments: non−castrated and slaughtered at 16 months of age (GL16), castrated at birth and slaughtered at 16 months of age (YL16), and castrated at birth and slaughtered at 26 months of age (YL26). The untargeted metabolome was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The transcriptome of the hepatic genes was analyzed to identify marbling-related genes. Using untargeted metabolomics, the main altered metabolic pathways in the liver of cattle, including those for lipid and amino acid metabolism, were detected in the YL16 group relative to the GL16 and YL26 groups. Significant increases in the presence of betaine, alanine, and glycerol 3-phosphate were observed in the YL16 group (p < 0.05), which might have contributed to the improved beef-marbling production. Compared to the GL16 and YL26 groups, significant increases in the presence of glutathione, acetylcarnitine, and riboflavin but decreases in diethanolamine and 2-hydroxyglutarate were identified in YL16 group (p < 0.05), which might have been beneficial to the beef's enhanced functional quality. The gene expressions of GLI1 and NUF2 were downregulated and that of CYP3A4 was upregulated in the YL16 group; these results were strongly correlated with the alanine, betaine, and leucine, respectively, in the liver of the cattle. In conclusion, implementation of early castration modified the hepatic metabolites and the related biological pathways by regulating the relevant gene expressions, which could represent a better rearing method for production of high marbled and healthier beef products. [ABSTRACT FROM AUTHOR]

Conventional terahertz (THz) waveform or spectral diagnostics mainly employ the electro-optic-based techniques or the multi-shot Michelson interferometer. Simultaneously, single-shot, ultrabroadband THz spectral measurements remain challenging. In this paper, a novel probe-free scheme based on the non-collinear autocorrelation technique is proposed to characterize the ultrabroadband THz spectrum at a single-shot mode. The non-collinear autocorrelator is a modified beam-division interferometer, in which the two beams are recombined non-collinearly onto a camera. The temporal or spectral resolution and range depend on the noncollinear configuration and camera parameters. This simple approach has been applied experimentally to characterize the ultrashort THz pulse generated from ultraintense laser–solid interactions, demonstrating the capability of single-shot ultrabroadband measurements without an auxiliary ultrafast laser probe. The proposed non-collinear autocorrelator here would be much useful for characterization and applications of low-repetition-rate intense THz sources and could also be extended to other frequency bands. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy of biofeedback and electrical stimulation-assisted pelvic floor muscle training (PFMT) between women with mild and moderate to severe stress urinary incontinence (SUI). Methods: This retrospective cohort study was conducted at a single center from 2014 to 2021. We included 57 patients with urodynamically proven SUI who underwent a biofeedback and electrical stimulation-assisted PFMT. They were categorized into mild and moderate to severe SUI. One-hour pad test from 2 to 10 g was defined as mild SUI, and ≥11 g was defined as moderate to severe SUI. Results: Fifty-seven patients were reviewed during the study period. Incontinence-related symptoms of distress, including the UDI-6, ISI, and VAS, all significantly improved in the mild SUI group (p = 0.001, p = 0.001 and p = 0.010, respectively), while only UDI-6 and VAS statistically improved in the moderate to severe SUI group (p = 0.027 and p = 0.010, respectively). There was significant improvement in IIQ-7 in the mild SUI group during serial treatments, but only in Session 6 in the moderate to severe SUI group. After 18 sessions of treatment, the UDI-6, ISI, and IIQ-7 scores showed significantly greater improvements in the mild SUI group compared to the moderate to severe SUI group (p = 0.003, p = 0.025, and p = 0.002, respectively). Conclusions: Although biofeedback and electrical stimulation-assisted PFMT is an effective treatment option for SUI, it is more beneficial for patients with mild SUI and a 1-h pad weight ≤ 10 g urine leak. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Prurigo nodularis is frequently difficult to manage with conventional therapy. Given the pathogenesis and refractory nature, we demonstrate a case in which inhibition of JAK–STAT signaling may significantly improve prurigo nodularis. Based on the results, we would like to draw a conclusion that abrocitinib as an inhibitor of Jak is a promising choice for the treatment of prurigo nodularis. [ABSTRACT FROM AUTHOR]

Background: The study examined the role of campus stressors and psychological pain on non-suicidal self-injury (NSSI) and suicide attempt (SA).Methods: Specific patterns of co-occurring psychological pain, campus stressors, and self-harm behaviors were identified by latent profile analysis, and their odds ratios (ORs) on NSSI and SA were analyzed in cross-sectional study and 2-year follow-up study. Structural Equation Model was used to explore indirect effect of campus stressors on SA and NSSI via different components of psychological pain.Results: Three classes were identified as low-risk class (68.58%) with low endorsements on the three measures, moderate-risk class (26.52%) with the elevated academic stressors, high levels of painful feelings, and high probabilities on NSSI; and high-risk class (4.90%) with the elevated combined stressors, high levels of pain avoidance, and high probabilities on SA. Compared to the moderate-risk class, adolescents in the high-risk class had a 4.97 OR of reporting NSSI, 17.98 OR of reporting SA. Pain avoidance class at baseline reported a higher probability in SA class (OR = 224.00) in a 2-year study.Conclusions: Painful feelings might be shared psychosocial correlates for NSSI and SA. However, pain avoidance may play a role in distinguishing SA from NSSI, which shed light on the intervention of adolescents who engage in self-harm behaviors. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the prevalence of metabolic disorders in patients with primary aldosteronism (PA) and target organ damage (TOD) in different subtypes of patients with PA with or without metabolic syndrome (MS). Patients with PA were screened out from those with secondary hypertension and then subtyped via adrenal venous sampling (AVS). Baseline clinical characteristics (blood pressure, blood glucose, abdominal circumference, and lipid profile) were collected for the diagnosis of MS. Organ damage was evaluated according to cardiac and carotid ultrasound and urine microalbumin measurements. In all 261 patients with PA, 113 patients had concomitant MS and experienced more severe cardiac hypertrophy and increased intima-media thickness (IMT). The incidence of MS and diabetes mellitus (DM) had no statistic difference between the two groups, moreover, the rates of TOD were not different except microalbuminuria. However, metabolic disorders caused more remarkable TOD in PA patients with unilateral hypersecretion. It showed that cardiac hypertrophy was associated with obesity while microalbuminuria was related to plasma aldosterone concentration (PAC) in PA patients. In this retrospective study, our findings suggest that the effect of metabolic disorders on organ damage is more remarkable in patients with unilateral PA. [ABSTRACT FROM AUTHOR]

The intrinsic assumption of radiogenic isotope tracing is that isotope systems maintain equilibrium between melt and source. However, this assumption is not naturally correct, particularly for S-type granites, which are formed by partial melting of metasedimentary rocks. The S-type metagranites from the North Qinling Terrane show various degrees of Hf Nd isotope decoupling and discrepancies between whole-rock and zircon Hf isotopes. Zircon U Pb dating yields emplacement ages from 946 to 890 Ma. Their high δ18O values, (87Sr/86Sr) i ratios, and negative ε Nd (t) values overlapped with metasedimentary rocks in the Qinling Group imply that they are derived from partial melting of the Qinling Group. The low Rb/Ba, Rb/Sr, Al 2 O 3 /TiO 2 , and high CaO/Na 2 O ratios indicate that their sources are metagraywackes. The negative correlation between decoupling degrees of Hf Nd isotopes and Zr concentrations suggests that the incomplete dissolution of zircon during partial melting results in the decoupling. The discrepancy between whole-rock and zircon Hf isotopes can be attributed to the combined effect of incomplete dissolution of zircons and the release of various Hf isotope compositions from partly dissolved inherited zircons to local melts. The compiled literature data suggest that whole-rock Hf Nd isotope decoupling of most metagraywacke-derived S-type granites is caused by incomplete melting of zircons, whereas those of metapelite-derived S-type granites may be controlled by both incomplete melting of zircons and source inheritance. • Incomplete melting of zircon causes Hf Nd isotope decoupling of S-type granites. • Partly dissolution of inherited zircon leads to whole-rock and zircon Hf difference. • Disequilibrium melting causes Hf Nd decoupling of all metagreywacke-derived granites. • Disequilibrium melting and sediment sorting both work for metapelite-derived granites. [ABSTRACT FROM AUTHOR]

The influence of initial curing temperature on the stability of calcium silicate hydrates (C-S-H) produced by alite hydration in the temperature range of 110 °C–240 °C was investigated. Test results showed that, alite pastes directly cured under high temperatures yielded dramatically faster crystallization of C-S-H compared to those precured at a low temperature of 80 °C before the high temperature curing. The direct high-temperature curing also resulted in simplified crystalline phase evolution with only α-C 2 SH produced below 200 °C. Detailed analyses employing XRD, TGA and MAS-NMR techniques revealed that the crystallization of C-S-H is accompanied by the increases of its Ca/Si and H 2 O/Si ratios as well as the reduction in the number of bridging tetrahedra in silicate chains. The decreased stability of C-S-H formed at direct high-temperature curing was probably induced by the generation of α-C 2 SH nuclei during the initial stages of alite hydration, enabling selective control of C-S-H crystallization. [ABSTRACT FROM AUTHOR]

We report the synthesis, structure, and electrochemical hydrogen evolution reaction (HER) performance of two alkynyl and halogen coprotected AuAg alloy nanoclusters, namely Au24Ag20(tBuPh-C≡C)24Cl2 (NC 1 for short) and Au22Ag22(tBuC≡C)16Br3.28Cl2.72 (NC 2 for short). Single crystal X-ray structural analysis revealed that the two nanoclusters possess a rather similar core@shell@shell keplerate metal core configuration to M12@M20@M12 with the main difference in the outermost shell (Au12vs. Au10Ag2). Interestingly, such a subtle difference in the two-metal-atoms results in different optical absorbance features and drastically different HER performances. Both NCs have excellent long-term stability for the HER, but NC 1 possesses superior activity to NC 2, and density functional theory calculations disclosed that the binding energy of hydrogen to form the key *H intermediate for NC 1 is much lower and hence it adopts a more energetically feasible HER pathway. [ABSTRACT FROM AUTHOR]

The Tibetan Plateau (TP) vortex (TPV), one of the crucial weather systems triggering rainfall, plays a key role in modulating precipitation over TP and downstream regions. The role of atmospheric heat source in TPV development is explored by a case study in June 2016, using high-resolution ERA5 reanalysis, black-body temperature (TBB) obtained from the Fengyun-2E (FY-2E) satellite, and precipitation amount from the Tropical Rainfall Measurement Mission (TRMM). The evolutions of TPV can be split into three stages, i.e., generation, development, and pre-moving-off stage. The intensity of TPV increases with fluctuations, with weaker and shallower TPV in the generation stage, strongest in the development stage and deepest in the pre-moving-off stage. Importantly, the genesis of TPV is related to the surface warming center driven by surface sensible heating while its development is primarily dependent on the latent heat of condensation. The main contributor of the latent heat of condensation is further analyzed as a vertical transport of the water vapor that promotes TPV development. [ABSTRACT FROM AUTHOR]

Introduction/Aims: In this study we aimed to determine the frequency of acetylcholine receptor (AChR) binding antibody positivity via neuroautoimmunity panel testing, and describe its occurrence in a group of nonmyasthenic disorders. Methods: This is a retrospective analysis of patients who underwent neuroautoimmunity antibody panel testing from 2010 to 2018 at the Cleveland Clinic. Results: A total of 10 855 patients received neuroautoimmunity antibody panel testing, and 224 (2.1%) patients were positive for AChR binding antibody. Fifty‐eight patients with a known myasthenia gravis (MG) diagnosis and 11 patients with incomplete follow‐up were excluded. Among the remaining 155 patients, 30 had newly diagnosed MG and 125 were nonmyasthenic. In 35 patients, MG was within the initial differential diagnosis based on the clinical presentation. In contrast to nonmyasthenic patients, myasthenic patients were more likely to have an initial clinical presentation raising suspicion for MG (73.3% vs 10.4%, P <.001), higher mean AChR binding antibody titer (8.2 ± 15.6 vs 0.4 ± 1.6 nmol/L, P =.011), and higher frequency of abnormal AChR modulating antibody (89.3% vs 23.9%, P <.001). A combination of AChR binding antibody of >0.5 nmol/L and modulating antibody of over 20% in patients with clinical suspicion of MG is virtually diagnostic of MG. A total of 31 (24.8%) nonmyasthenic patients carried coexisting autoimmune conditions. Discussion: Elevated titers of AChR binding antibody can sometimes be found in nonmyasthenic patients. Combined analysis of clinical presentation, AChR binding antibody titer, and AChR‐modulating antibody results can be helpful in confirming an MG diagnosis. See Editorial on pages 489–491 in this issue [ABSTRACT FROM AUTHOR]

Sodium zirconium cyclosilicate (SZC) is an effective potassium binder for patients with hyperkalemia. This single‐center, open‐label, phase I study (NCT03283267) characterized the pharmacodynamics and safety of SZC in Chinese individuals. Twenty‐two healthy Chinese adults (mean age, 33.5 years) randomized 1:1 received daily oral SZC 5 or 10 g for 4 days, following 4 days on a low‐sodium, high‐potassium diet (continued throughout the study). End points were mean change from baseline in 24‐hour urinary potassium (primary) and sodium excretion, and serum potassium concentration. Urinary potassium excretion significantly decreased with SZC 5 g (mean change [mmol], –13.0; P <.001) and 10 g (–15.4; P <.001). Although urinary sodium excretion decreased significantly with SZC 5 g (–11.5; P =.030), there was no significant change with SZC 10 g (–5.1; P =.299). Serum potassium concentrations decreased significantly with SZC 5 g (–0.14; P =.031) and 10 g (–0.20; P =.002). All treatment‐emergent adverse events were mild, and none were considered causally related to SZC. Over 4 days, the pharmacodynamics and safety of SZC were consistent in healthy Chinese adults with global studies and patients of Japanese ethnicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Suppressing eEF2K in hepatocellular carcinoma led to increased NK cell infiltration and activity. • Inhibition of eEF2K expression in hepatocellular carcinoma cells activated the cGAS–STING pathway. • Blocking eEF2K enhanced viability and reduced apoptosis in NK cells. • eEF2K, a potential therapeutic target for HCC, showed correlations with immune regulatory factors. Liver cancer, particularly hepatocellular carcinoma (HCC), is characterized by a high mortality rate, attributed primarily to the establishment of an immunosuppressive microenvironment. Within this context, we aimed to elucidate the pivotal role of eukaryotic elongation factor 2 kinase (eEF2K) in orchestrating the infiltration and activation of natural killer (NK) cells within the HCC tumor microenvironment. By shedding light on the immunomodulatory mechanisms at play, our findings should clarify HCC pathogenesis and help identify potential therapeutic intervention venues. We performed a comprehensive bioinformatics analysis to determine the functions of eEF2K in the context of HCC. We initially used paired tumor and adjacent normal tissue samples from patients with HCC to measure eEF2K expression and its correlation with prognosis. Subsequently, we enrolled a cohort of patients with HCC undergoing immunotherapy to examine the ability of eEF2K to predict treatment efficacy. To delve deeper into the mechanistic aspects, we established an eEF2K-knockout cell line using CRISPR/Cas9 gene editing. This step was crucial for verifying activation of the cGAS–STING pathway and the subsequent secretion of cytokines. To further elucidate the role of eEF2K in NK cell function, we applied siRNA-based techniques to effectively suppress eEF2K expression in vitro. For in vivo validation, we developed a tumor-bearing mouse model that enabled us to compare the infiltration and activation of NK cells within the tumor microenvironment following various treatment strategies. We detected elevated eEF2K expression within HCC tissues, and this was correlated with an unfavorable prognosis (30.84 vs. 20.99 months, P = 0.033). In addition, co-culturing eEF2K-knockout HepG2 cells with dendritic cells led to activation of the cGAS–STING pathway and a subsequent increase in the secretion of IL-2 and CXCL9. Moreover, inhibiting eEF2K resulted in notable NK cell proliferation along with apoptosis reduction. Remarkably, after combining NH125 and PD-1 treatments, we found a significant increase in NK cell infiltration within HCC tumors in our murine model. Our flow cytometry analysis revealed reduced NKG2A expression and elevated NKG2D expression and secretion of granzyme B, TNF-α, and IFN-γ in NK cells. Immunohistochemical examination confirmed no evidence of damage to vital organs in the mice treated with the combination therapy. Additionally, we noted higher levels of glutathione peroxidase and lipid peroxidation in the peripheral blood serum of the treated mice. Targeted eEF2K blockade may result in cGAS–STING pathway activation, leading to enhanced infiltration and activity of NK cells within HCC tumors. The synergistic effect achieved by combining an eEF2K inhibitor with PD-1 antibody therapy represents a novel and promising approach for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Purpose: Given the popularity of empowerment practices among scholars and practitioners, this research examines whether a manager's differentiated empowering leadership negatively affects team members' helping behaviors and, if so, how. Methods: The authors conducted one multi-source and time-lagged survey (with 44 managers and 212 team members) and two scenario-based experiments (with 120 participants in Study 2 and 121 participants in Study 3) to test the research model. Results: Team managers' differentiated empowering leadership decreases team members' helping behaviors. In particular, for team members who receive less empowerment, differentiated empowering leadership may decrease their helping behaviors by eliciting their envy. For team members who receive more empowerment, differentiated empowering leadership may decrease their helping behaviors by inducing their contempt. Conclusion: This research introduces the concept of differentiated empowering leadership in response to calls to investigate the dark side of empowering leadership. It reveals that unequal distribution of authority among team members by managers can undermine employee relations and elicit negative emotions of envy and contempt, thereby decreasing employees' helping behaviors. [ABSTRACT FROM AUTHOR]

Interferon (IFN) and nucleoside (nucleotide) analogs (NAs) are two effective antiviral drugs for chronic hepatitis B (CHB). More and more evidence shows that the combination of the two drugs can better inhibit viral replication and even achieve clinical cure. IFN intermittent therapy is also considered to be an important measure to resolve IFN fatigue when hepatitis B surface antigen (HBsAg) decline appears stagnated during IFN-based antiviral therapy. A 36-year-old male NA-experienced patient with hepatitis B e antigen (HBeAg)-positive CHB was admitted to our hospital. After a poor response to tenofovir disoproxil fumarate (TDF) monotherapy for 1 year, the patient was treated with pegylated interferon alfa-2a combination therapy and finally achieved HBsAg clearance. During the treatment and follow-up, HBsAg, HBeAg, hepatitis B virus (HBV) DNA, and serum alanine aminotransferase, etc. were monitored every 3 months. Between weeks 58 and 71 of combination therapy, IFN was discontinued because of a slow decline in HBsAg, and TDF alone was used for maintenance therapy. Complete virological response, HBeAg and HBsAg seroconversion were observed at weeks 44, 96, and 122, respectively. After 24 weeks of consolidation therapy, HBsAg, HBeAg, and HBV DNA were consistently negative, and hepatitis B surface antibody was 729.30 mIU/mL at week 146 of the combination therapy, then we stopped drugs. Following up after 28 weeks of cessation therapy, the patient still remained clinically cured. [ABSTRACT FROM AUTHOR]

We report the fabrication of homoleptic alkynyl‐protected Ag15(C≡C‐tBu)12+ (abbreviated as Ag15) nanocluster and its electrocatalytic properties toward CO2 reduction reaction. Crystal structure analysis reveals that Ag15 possesses a body‐centered‐cubic (BCC) structure with an Ag@Ag8@Ag6 metal core configuration. Interestingly, we found that Ag15 can adsorb CO2 in the air and spontaneously self‐assembled into one‐dimensional linear material during the crystal growth process. Furthermore, Ag15 can convert CO2 into CO with a faradaic efficiency of ca. 95.0 % at −0.6 V and a maximal turnover frequency of 6.37 s−1 at −1.1 V along with excellent long‐term stability. Finally, density functional theory (DFT) calculations disclosed that Ag15(C≡C‐tBu)11+ with one alkynyl ligand stripping off from the intact cluster can expose the uncoordinated Ag atom as the catalytically active site for CO formation. [ABSTRACT FROM AUTHOR]

We report the fabrication of homoleptic alkynyl‐protected Ag15(C≡C‐tBu)12+ (abbreviated as Ag15) nanocluster and its electrocatalytic properties toward CO2 reduction reaction. Crystal structure analysis reveals that Ag15 possesses a body‐centered‐cubic (BCC) structure with an Ag@Ag8@Ag6 metal core configuration. Interestingly, we found that Ag15 can adsorb CO2 in the air and spontaneously self‐assembled into one‐dimensional linear material during the crystal growth process. Furthermore, Ag15 can convert CO2 into CO with a faradaic efficiency of ca. 95.0 % at −0.6 V and a maximal turnover frequency of 6.37 s−1 at −1.1 V along with excellent long‐term stability. Finally, density functional theory (DFT) calculations disclosed that Ag15(C≡C‐tBu)11+ with one alkynyl ligand stripping off from the intact cluster can expose the uncoordinated Ag atom as the catalytically active site for CO formation. [ABSTRACT FROM AUTHOR]

The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C−p−NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher‐energy emission peak of Cu4 gradually disappeared, leaving the lower‐energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle‐dispersive synchrotron X‐ray diffraction results revealed that the reduced inter‐cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C−H⋅⋅⋅N and N−H⋅⋅⋅N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands′ vibration, resulting in the vanishing of the higher‐energy peak. In situ high‐pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4. [ABSTRACT FROM AUTHOR]

The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C−p−NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher‐energy emission peak of Cu4 gradually disappeared, leaving the lower‐energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle‐dispersive synchrotron X‐ray diffraction results revealed that the reduced inter‐cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C−H⋅⋅⋅N and N−H⋅⋅⋅N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands′ vibration, resulting in the vanishing of the higher‐energy peak. In situ high‐pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4. [ABSTRACT FROM AUTHOR]

Progress in the discovery of potent antibodies for therapeutic and research purposes has been accelerated by mining the antibody repertoire of plasma cells and plasmablasts. Magnetic activated cell sorting (MACS) is a well recognized method for cell sorting, however, secreted IgGs rapidly diffuse away from cells, therefore requiring specialized technique to compartmentalize individual cells and capture their secretions for MACS isolation. To this end, a scalable method to prepare hydrogel‐based microcontainers for single cell culture and subsequent sorting based on their secreted IgG products at high‐throughput level are described. In situ crosslinkable microgels featuring tunable viscosity are fabricated to act as soft compartments that accommodate delicate primary cells and capture secreted proteins, while providing solid supports after solgel transition to enable immune recognition with chemically functionalized magnetic nanorods in aqueous medium for MACS separation. Splenocytes are sorted based on antigen‐specific IgG production from mice immunized with an antibiotic target ceftriaxone sodium, enriching a population of 220 000 000 to 800 000 prevalence following sorting. This enrichment ratio is substantially higher than conventional fluorescence activated cell sorting (FACS) methods, likely due to the multivalency of the antigen‐conjugated magnetic nanorods. [ABSTRACT FROM AUTHOR]

Metal nanoclusters, also known as ultra-small metal nanoparticles, occupy the gap between discrete atoms and plasmonic nanomaterials, and are an emerging class of atomically precise nanomaterials. Metal nanoclusters protected by different types of ligands, such as thiolates, alkynyls, hydrides, and N-heterocyclic carbenes, have been synthesized in recent years. Moreover, recent experiment and theoretical studies also indicated that the metal nanoclusters show great promise in many electrocatalytic reactions, such as hydrogen evolution, oxygen reduction, and CO2 reduction. The atomically precise nature of their structures enables the elucidation of structure-property relationships and the reaction mechanisms, which is essential if nanoclusters with enhanced performances are to be rationally designed. Particularly, the ligands play an important role in affecting the interface bonding, stability and electrocatalytic activity/selectivity. In this review, we mainly focus on the ligand effect on the interface structure of metal nanoclusters and then discuss the recent advances in electrocatalytic applications. Furthermore, we point out our perspectives on future efforts in this field. [ABSTRACT FROM AUTHOR]

Background: Primary aldosteronism (PA) is highly prevalent in hypertensive population. Adrenal vein sampling (AVS) is the only procedure to assess adrenal aldosterone hypersecretion in PA. PA patients without aldosterone-producing adenomas (APA) frequently have unilateral aldosterone hypersecretion (UAH). These patients could bear inappropriate adrenalectomy without AVS. This study aims to identify which clinical characteristics should be recommended to perform AVS in these PA patients. Methods: This study was performed from January 2018 to July 2019 at a center for hypertension and metabolic diseases. Adrenal computed tomography (CT) scan, biochemical evaluation, and AVS were performed. Results: Total 141 patients were included in this study. Aldosterone to renin ratio (ARR) after confirmatory test is highly associated with adrenal laterality. The specificity of ARR > 10 (ng/dL)/(mU/L) after confirmatory test is 100%. After confirmatory test, patients with ARR > 10 (ng/dL)/(mU/L) had higher plasma aldosterone concentration and incidences of ischemic heart diseases and renal damage(p < 0.05). Conclusions: After confirmatory tests, ARR > 10 (ng/dL)/(mU/L) indicates adrenal laterality, with increasingly cardiorenal damage in PA patients without APA. Thus, AVS should be recommended in these patients before surgery. Trial registration: NCT03398785, Date of Registration: December 24, 2017. [ABSTRACT FROM AUTHOR]

The low immunogenicity, insufficient infiltration of T lymphocytes, and dismal response to immune checkpoint blockade therapy pose major difficulties in immunotherapy of pancreatic cancer. Photoimmunotherapy by photodynamic therapy (PDT) can induce an antitumor immune response by triggering immunogenic cell death in the tumor cells. Notwithstanding, PDT‐driven oxygen consumption and microvascular damage can further aggravate hypoxia to exaggerates glycolysis, leading to lactate accumulation and immunosuppressive tumor microenvironment. Herein, a supramolecular prodrug nanoplatform codelivering a photosensitizer and a prodrug of bromodomain‐containing protein 4 inhibitor (BRD4i) JQ1 for combinatory photoimmunotherapy of pancreatic cancer are demonstrated. The nanoparticles are fabricated by host–guest complexation between cyclodextrin‐grafted hyaluronic acid (HA‐CD) and adamantine‐conjugated heterodimers of pyropheophorbide a (PPa) and JQ1, respectively. HA can achieve active tumor targeting by recognizing highly expressed CD44 on the surface of pancreatic tumors. PPa‐mediated PDT can enhance the immunogenicity of the tumor cells and promote intratumoral infiltration of the cytotoxic T lymphocytes. Meanwhile, JQ1 combats PDT‐mediated immune evasion through inhibiting expression of c‐Myc and PD‐L1, which are key regulators of tumor glycolysis and immune evasion. Collectively, this study presents a novel strategy to enhance photoimmunotherapy of the pancreatic cancer by provoking T cells activation and overcoming adaptive immune resistance. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infections in infants and children. Currently, no approved HMPV vaccine is available. We developed a novel recombinant influenza virus, which carried partial HMPV F protein (HMPV-F) epitopes, utilizing reverse genetics. The novel single-stranded RNA virus, termed rFLU-HMPV/F-NA, was synthesized in the neuraminidase (NA) fragment of influenza virus A/PuertoRico/8/34 (PR8). The morphological characteristics of rFLU-HMPV/F-NA were consistent with the wild-type flu virus. The virus could passage in specific pathogen-free (SPF) chicken embryos for at least five consecutive generations with haemagglutinin (HA) titres of 28–9 or 8–9LogTCID50/mL. BALB/c mice were intranasally immunized at 21-day intervals with 104 TCID50 (low-dose group) or 106 TCID50 (high-dose group) rFLU-HMPV/F-NA, and PBS or PR8 vaccine was used for the control group. rFLU-HMPV/F-NA induced robust humoral, mucosal, and cellular immune responses in vivo in a dose-dependent manner. More importantly, wt clinical HMPV isolate challenge studies showed that rFLU-HMPV/F-NA provided significant immune protection against HMPV infection compared to the PBS or PR8 vaccine control group, as shown by improved histopathological changes and reduced viral titres in the lungs of immunized mice post-challenge. These findings demonstrate that rFLU-HMPV/F-NA has potential as a promising HMPV candidate vaccine and warrants further investigation into its control of HMPV infection. [ABSTRACT FROM AUTHOR]

Simple Summary: In current pig farming, pigs are susceptible to stress-induced adverse emotions. Emotional contagion may propagate these emotions within a herd, potentially affecting overall welfare. Typically, treatments of individual pigs should be conducted separately from the group. Thus, after separation from treatment on an individual pig, the behavioral responses and heart rate changes of the companion pig were recorded to determine if the sensory avoidance was effective. It was found that peers were still affected by the treated pigs after sensory avoidance. Separation from treatment does not eliminate the effects of the treated pig on companion pigs, which can still be affected in post-treatment contact. In the pig farming industry, it is recommended to avoid groups when treating individuals to reduce adverse reactions in the group. However, can this eliminate the adverse effects effectively? Piglets were assigned to the Rewarding Group (RG), the Punishing Group (PG), and the Paired Control Group (PCG). There were six replicates in each group, with two paired piglets per replicate. One piglet of the RG and PG was randomly selected as the Treated pig (TP), treated with food rewards or electric shock, and the other as the Naive pig (NP). The NPs in the RG and PG were unaware of the treatment process, and piglets in the PCG were not treated. The behavior and heart rate changes of all piglets were recorded. Compared to the RG, the NPs in the PG showed longer proximity but less contact behavior, and the TPs in the PG showed more freezing behavior. The percentage change in heart rate of the NPs was synchronized with the TPs. This shows that after sensory avoidance, the untreated pigs could also feel the emotions of their peers and their emotional state was affected by their peers, and the negative emotions in the pigs lasted longer than the positive emotions. The avoidance process does not prevent the transfer of negative emotions to peers via emotional contagion from the stimulated pig. [ABSTRACT FROM AUTHOR]

Atomically precise metal nanoclusters (NCs) have emerged as a promising frontier in the field of electrochemical CO2 reduction reactions (CO2RR) because of their distinctive catalytic properties. Although numerous metal NCs are developed for CO2RR, their use in practical applications has suffered from their low‐yield synthesis and insufficient catalytic activity. In this study, the large‐scale synthesis and electrocatalytic performance of ClAg14(C≡CtBu)12+ NCs, which exhibit remarkable efficiency in catalyzing CO2‐to‐CO electroreduction with a CO selectivity of over 99% are reported. The underlying mechanisms behind this extraordinary CO2RR activity of ClAg14(C≡CtBu)12+ NCs are investigated by a combination of electrokinetic and theoretical studies. These analyses reveal that different active sites, generated through electrochemical activation, have unique adsorption properties for the reaction intermediates, leading to enhanced CO2RR and suppressed hydrogen production. Furthermore, industrially relevant CO2‐to‐CO electroreduction using ClAg14(C≡CtBu)12+ NCs in a zero‐gap CO2 electrolyzer, achieving high energy efficiency of 51% and catalyst activity of over 1400 A g−1 at a current density of 400 mA cm−2 is demonstrated. [ABSTRACT FROM AUTHOR]

2D metal‐organic frameworks (MOFs) have attracted broad research interest in recent years owing to their unique dimension‐related properties for widespread applications in catalysis, energy storage, conductivity, and optoelectronic devices. In this review, first the strategies for the rational design and precise construction of 2D MOFs are introduced. Then, the synthesis of 2D MOFs and their nanosheets by using top‐down and bottom‐up methods are summarized. Subsequently, the recent advances in optical/photonic applications of these 2D MOFs are highlighted, with special focus on lighting and display devices, nonlinear optics, as well as the luminescent sensing and biomedicine applications. Finally, the future potentials and challenges for the construction of 2D MOFs for optical materials are outlooked. [ABSTRACT FROM AUTHOR]

Silicon is widely studied as a high-capacity lithium-ion battery anode. However, the pulverization of silicon caused by a large volume expansion during lithiation impedes it from being used as a next generation anode for lithium-ion batteries. To overcome this drawback, we synthesized ultrathin silicon nanowires. These nanowires are 1D silicon nanostructures fabricated by a new bi-metal-assisted chemical etching process. We compared the lithium-ion battery properties of silicon nanowires with different average diameters of 100 nm, 30 nm and 10 nm and found that the 30 nm ultrathin silicon nanowire anode has the most stable properties for use in lithium-ion batteries. The above anode demonstrates a discharge capacity of 1066.0 mAh/g at a current density of 300 mA/g when based on the mass of active materials; furthermore, the ultrathin silicon nanowire with average diameter of 30 nm anode retains 87.5% of its capacity after the 50th cycle, which is the best among the three silicon nanowire anodes. The 30 nm ultrathin silicon nanowire anode has a more proper average diameter and more efficient content of SiOx. The above prevents the 30 nm ultrathin silicon nanowires from pulverization and broken during cycling, and helps the 30 nm ultrathin silicon nanowires anode to have a stable SEI layer, which contributes to its high stability. Silicon nanowires (SiNWs) with average diameters of 10 nm, 30 nm and 100 nm were produced through bi-metal-assisted chemical etching method and metal-assisted chemical etching method. The 30 nm SiNWs anode showed a more stable LIB property than the 10 nm and 100 nm SiNWs anodes. [ABSTRACT FROM AUTHOR]

Oncolytic viruses are able to lyse tumor cells selectively in the liver without killing normal hepatocytes, in addition to activating the immune response. Oncolytic virus therapy is expected to revolutionize the treatment of liver cancer, including hepatocellular carcinoma (HCC), one of the most frequent and fatal malignancies. In this study, reverse genetics techniques were exploited to load NA fragments of the A/PuertoRico/8/34 virus (PR8) with GV1001 peptides derived from human telomerase reverse transcriptase. An in vitro assessment of the therapeutic effect of the recombinant oncolytic virus was followed by an in vivo study in mice with HCC. The recombinant virus was verified by sequencing of the recombinant viral gene sequence, and viral virulence was detected by hemagglutination assays and based on the 50% tissue culture infectious dose (TCID50). The morphological structure of the virus was observed by electron microscopy, and GV1001 peptide was localized by cellular immunofluorescence. The selective cytotoxicity of the recombinant oncolytic virus in vitro was demonstrated in cultured HCC cells and normal hepatocytes, as only the tumor cells were killed; the normal cells were not significantly altered. Consistent with the in vitro results, the recombinant oncolytic influenza virus significantly inhibited liver tumor growth in mice in vivo, in addition to inducing an antitumor immune response, including an increase in the number of CD4+ and CD8+ T lymphocytes and, in turn, improving survival. Our results suggest that oncolytic influenza virus carrying GV1001 is a promising immunotherapy in patients with HCC. [ABSTRACT FROM AUTHOR]

Objectives: To date, the effectiveness of acceptance and commitment therapy (ACT) for acute stroke patients has not been well recognized. The study aimed to discover the effectiveness of group‐based ACT in treating depression for acute stroke patients. Methods: We conducted a randomized controlled trial with 140 acute stroke patients with depression. The ACT intervention comprised seven sessions, of 45–60 min over 4 weeks. Data were collected pre‐ and post‐intervention and at 3‐month follow‐up, assessing depression, health‐related quality of life (HRQoL), psychological flexibility, cognitive fusion, sleep quality, and confidence. Results: Overall, 99.3% of the included patients were assessed as having mild depression. The ACT intervention significantly reduced depression in acute stroke patients in comparison with the control group post‐intervention and at 3 months (partial η2=.306$\eta^{2}=.306$). Additionally ACT significantly improved HRQoL‐mental component summary, sleep quality, psychological flexibility, cognitive fusion, and confidence compared with control group. Conclusions: ACT is effective in treating acute stroke patients with depression, and the efficacy was maintained at 3‐month follow‐up. [ABSTRACT FROM AUTHOR]

The finite element method (FEM) is employed to analyze the residual stress distribution of bi-layer (a-SiC + diamond) film system, and the adhesion enhancement mechanism of a-SiC interlayer is further investigated. The influence of a-SiC interlayer on the surface topography of WC-Co substrate is taken into consideration by adopting a 3D surface topography model agreeing with the Atomic Force Microscope (AFM) characterization of a-SiC interlayer. For the sake of comparison, the stress distribution of a diamond film with no interlayer is also simulated. The simulation analysis reveals that the residual stress distribution is much more homogeneous after employing the a-SiC interlayer, which is supposed to be of great importance to the adhesion enhancement of diamond films. Afterwards, the diamond films with and without a-SiC interlayer are fabricated on WC-Co substrates. Raman mapping is carried out to measure the real residual stress distribution of as-fabricated a-SiC diamond films, which is in accordance with the simulation results. Moreover, the a-SiC interlayered diamond film exhibits better adhesion than the diamond film with no interlayer in adhesion evaluation, which can be ascribed to the more homogeneous residual stress distribution and better interfacial bonding after introducing the a-SiC interlayer. [ABSTRACT FROM AUTHOR]

Bread wheat (AABBDD) originated from the diploid progenitor Triticum urartu (AA), a relative of Aegilops speltoides (BB), and Ae. tauschii (DD). The DREB1 transcriptional factor plays key regulatory role in low-temperature tolerance. The modern breeding strategies resulted in serious decrease of the agricultural biodiversity, which led to a loss of elite genes underlying abiotic stress tolerance in crops. However, knowledge of this gene’s natural diversity is largely unknown in the genome donor species of wheat. We characterized the dehydration response element binding protein 1 (DREB1) gene-diversity pattern in Ae. speltoides, Ae. tauschii, T. monococcum and T. urartu. The highest nucleotide diversity value was detected in Ae. speltoides, followed by Ae. tauschii and T. monococcum. The lowest nucleotide diversity value was observed in T. urartu. Nucleotide diversity and haplotype data might suggest no reduction of nucleotide diversity during T. monococcum domestication. Alignment of the 68 DREB1 sequences found a large-size (70 bp) insertion/deletion in the accession PI486264 of Ae. speltoides, which was different from the copy of sequences from other accessions of Ae. speltoides, suggesting a likely existence of two different ancestral Ae. speltoides forms. Implication of sequences variation of Ae. speltoides on origination of B genome in wheat was discussed. [ABSTRACT FROM AUTHOR]

In this study, CuO films with hollow cubic cages were prepared by a facile two-step procedure consisting of electrodeposition synthesis and subsequent direct calcination. First, Cu2O nanocubes were fabricated on ITO substrate through a simple electrodeposition procedure. Then, Cu2O nanocubes were converted to CuO hollow cubic cages without obvious morphological change through direct calcination. The obtained CuO cubic cages serving as active materials illustrated a favorable performance for nonenzymatic glucose sensing with high sensitivity of 2 1 1 7. 4 4 μ A mM − 1 cm − 2 at a low applied potential of 0.50 V, fast-response time (less than 3 s), low detection limit of 1.0 μ M and wide linear range up from 2.0 μ M to 1.0 mM ( R 2 = 0. 9 9 8 3). Moreover, the good selectivity of the CuO cubic cages-based nonenzymatic glucose sensor against electroactive compounds such as ascorbic acid, uric acid and dopamine were also demonstrated. These good features indicate that the as-prepared CuO cubic cages can be used as promising electrode materials, which have a great potential in the development of sensitive and selective nonenzymatic glucose sensors. CuO films, with hollow cubic cages, were prepared by a facile two-step procedure consisting of electrodepositon Cu2O film and converted to CuO films by subsequent direct calcination. When used as electrode, such CuO film modified ITO substrate exhibits a favorable performance for nonenzymatic glucose sensing attributed to its open structure with larger specific area. The CuO hollow cubic cages structures should be applied in other fields, such as solar-energy conversion and gas sensors. [ABSTRACT FROM AUTHOR]

If a finite group G acts topologically and faithfully on ℝ 3 ⁠, then G is isomorphic to a subgroup of O (3). [ABSTRACT FROM AUTHOR]