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Extremely cold exposure causes human physiological changes and has implications for human health and occupational safety. In this paper, a multi-segmented human bioheat model is developed for predicting human thermoregulatory and physiological responses, especially those of the extremities, under both cold and extremely cold environments. The novel improvements in the model include: 1) the segmental energy balance equations are improved for an extended 22 human body segments; 2) the current model represents the effect of the skin perfusion blood flow on the heat conduction between the skin and core, and further considering the superficial vein blood in peripheral segments (forearms, calves, hands, feet and fingers) and modifying dimensions of the fingers, a more realistic circulatory blood flow system is implemented; 3) the thermoregulatory control equations reflecting the characteristics of human physiological responses to both cold and extremely cold exposure are implemented, including arteriovenous anastomoses (AVAs) in the extremities (feet and fingers), the local skin blood flow decreases by vasoconstriction, and the heat production by shivering. The proposed model is validated and evaluated by comparing the previous models and the published experimental data at a variety of conditions and activity. Furthermore, the experiments on human physiological responses under a range of cold exposures (−5 °C, −10 °C and −15 °C) are conducted in this study, and good agreements between the experimental data of core and skin temperatures and the predicted values of the current model are observed. [ABSTRACT FROM AUTHOR]

The present study was designed to explore the pharmacokinetics and tissue distribution levels of sarafloxacin hydrochloride in the pacific white shrimp, Litopenaeus vannamei , after oral administration of multiple doses (30 mg/kg, twice a day for 5 days). Eighteen shrimps per sampling point were examined during and after treatment. Sarafloxacin hydrochloride concentrations in the hemolymph, hepatopancreas, and muscle of the pacific white shrimp were determined using HPLC. Pharmacokinetic parameters were analyzed based on the statistical moment theory. The results showed rapid absorption of sarafloxacin hydrochloride in hepatopancreas, hemolymph, and muscles (T max = 2 h) after oral administration. Sarafloxacin hydrochloride peak concentration in the hemolymph, hepatopancreas, and muscle were 12.236 mg/L, 376.939 mg/kg, and 6.17 mg/kg, respectively. Tissue distribution (AUC) 0-∞ followed the order hepatopancreas > hemolymph > muscle, indicating the hepatopancreas was the main organ involved in sarafloxacin hydrochloride metabolism in the pacific white shrimp. After multiple-dose oral administration, some accumulation occurred in the hepatopancreas, while in the hemolymph and muscle, sarafloxacin hydrochloride reached a steady state following multiple-dose administration. The t 1/2z values of sarafloxacin hydrochloride in hemolymph, hepatopancreas, and muscle were 27.403 h, 20.456 h, and16.852 h, respectively. The values of AUC ss , C trough , and C av were graded as hepatopancreas > hemolymph > muscle, showing hepatopancreas played an important role in drug metabolism and elimination in shrimp. In addition, the withdrawal period of 4 days after the last oral medication was recommended based on the calculated value of WT1.4 software and the actual detected value of sarafloxacin hydrochloride in the muscle of the pacific white shrimp. When Vibrio parahaemolyticus was used as an indicator, the ratio of AUC 0-t /MIC 90 and C max /MIC 90 were 101.15 and 12.24, respectively. • Pharmacokinetics of sarafloxacin hydrochloride was explored. • Some accumulation of sarafloxacin hydrochloride occurred in the hepatopancreas. • Multiple-dose administration has better effect on the treatment of pathogens. [ABSTRACT FROM AUTHOR]

Objectives: Patients in cognitive behavioural therapy (CBT) who are high in interpersonal sensitivity may have difficulty fully engaging in treatment because therapy sessions require intimate interpersonal interactions that are especially uncomfortable for these individuals. The current study tests the hypotheses that patients who are high in interpersonal sensitivity benefit less from CBT for symptoms of depression and anxiety, show a slower rate of change in those symptoms, and are more likely to drop out of treatment., Methods: Participants were 832 outpatients who received naturalistic CBT. We assessed interpersonal sensitivity before treatment began and depression and anxiety symptoms at every therapy session. We assessed early, premature, and uncollaborative termination after treatment ended. We constructed multilevel linear regression models and logistic regression models to assess the effects of baseline interpersonal sensitivity on the treatment outcome, the slope of change in depression and anxiety symptoms, and each type of dropout., Results: Higher baseline interpersonal sensitivity was associated with a slower rate of change and less overall change in anxiety but not depressive symptoms. Baseline interpersonal sensitivity was not a predictor of dropout., Conclusions: Interpersonal sensitivity at baseline predicts less change and a slower rate of change in anxiety symptoms. Early detection of elevated interpersonal sensitivity can help therapists take action to address these barriers to successful treatment and help scientists build decision support tools that accurately predict the trajectory of change in anxiety symptoms for these patients., (© 2024 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Introduction: Porcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts., Methods: This research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis., Results: We discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-β through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection., Discussion: Our findings initially provide the validation of MRPS6 as an upstream component of IFN-β pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-β production of HIEC-6 via dual-activation from interferon pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Zhang, Li, Chen, Hao, Gao, Hao, Xu, Wang, Li and Jin.)

Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) by analyzing the transcriptome at different time points post-infection (12 h, 24 h, 48 h). Differential gene analysis revealed a total of 3560, 5193, and 4147 differentially expressed genes (DEGs) at 12 h, 24 h, and 48 h, respectively. The common genes among the DEGs at all three time points were enriched in biological processes related to cytokine production, extracellular matrix, and cytokine activity. KEGG pathway analysis showed enrichment of genes involved in the p53 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. Further analysis of highly expressed genes among the DEGs identified significant changes in the expression levels of BUB1, DDIT4, ATF3, GBP2, and IRF1. Comparison of transcriptome data at 24 h with other time points revealed 298 DEGs out of a total of 6276 genes. KEGG analysis of these DEGs showed significant enrichment of pathways related to viral infection, specifically the PI3K-Akt and P38 MAPK pathways. Furthermore, the genes EFNA1 and KITLG, which are associated with viral infection, were found in both enriched pathways, suggesting their potential as therapeutic or preventive targets for PDCoV infection. The enhancement of PDCoV infection in HIEC-6 was observed upon inhibition of the PI3K-Akt and P38 MAPK signaling pathways using sophoridine. Overall, these findings contribute to our understanding of the molecular mechanisms underlying PDCoV infection in HIEC-6 cells and provide insights for developing preventive and therapeutic strategies against PDCoV infection.

Colloidal quantum dot (CQD) infrared (IR) photodetectors can be fabricated and operated with larger spectral tunability, fewer limitations in terms of cooling requirements and substrate lattice matching, and at a potentially lower cost than detectors based on traditional bulk materials. Silver selenide (Ag 2 Se) has emerged as a promising sustainable alternative to current state-of-the-art toxic semiconductors based on lead, cadmium, and mercury operating in the IR. However, an impeding gap in available absorption bandwidth for Ag 2 Se CQDs exists in the short-wave infrared (SWIR) region due to degenerate doping by the environment, switching the CQDs from intrinsic interband semiconductors in the near-infrared (NIR) to intraband absorbing CQDs in the mid-wave infrared (MWIR). Herein, we show that the small molecular p-type dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) can be used to extract electrons from the 1S e state of MWIR active Ag 2 Se CQDs to activate their intrinsic energy gap in the SWIR window. We demonstrate quenching of the MWIR Ag 2 Se absorbance peak, shifting of nitrile vibrational peaks characteristic of charge-neutral F4-TCNQ, as well as enhanced CQD absorption around ∼2500 nm after doping both in ambient and under air-free conditions. We elucidate the doping mechanism to be one that involves an integer charge transfer akin to doping in semiconducting polymers. These indications of charge transfer are promising milestones on the path to achieving sustainable SWIR Ag 2 Se CQD photodetectors., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Avipoxvirus 282E4 strain was extensively applied into recombinant vaccine vector to prevent other infectious diseases. However, little information on the genomic background, functional and genetic evolutionary of the isolate 282E4 strain was clarified. The results showed that the linear genome of avipoxvirus 282E4 was 308,826 bp, containing 313 open reading frames (ORFs) and 12 new predicted ORFs. The 282E4 strain appears to encode two novel thymidine kinase proteins and two TGF-beta-like proteins that may be associated with the suppression of the host's antiviral response. Avipoxvirus 282E4 also encodes 57 ankyrin repeat proteins and 5 variola B22R-like proteins, which composed 7% of the avipoxvirus 282E4 genome. GO and KEGG analysis further revealed that 12 ORFs participate in viral transcription process, 7 ORFs may function during DNA repair, replication and biological synthesis, and ORF 208 is involved in the process of virus life cycle. Interestingly, phylogenetic analysis based on concatenated sequences p4b and DNA polymerase of avipoxviruses gene demonstrates that avipoxvirus 282E4 strain is divergent from known FWPV isolates and is similar to shearwater poxvirus (SWPV-1) that belongs to the CNPV-like virus. Sequencing avipoxvirus 282E4 is a significant step to judge the genetic position of avipoxviruses within the larger Poxviridae phylogenetic tree and provide a new insight into the genetic background of avipoxvirus 282E4 and interspecies transmission of poxviruses, meanwhile, explanation of gene function provides theoretical foundation for vaccine design with 282E4 strain as skeleton., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs., (© 2023. Springer Nature Limited.)

Deoxynivalenol is one of the most widely distributed mycotoxins in cereals and poses tremendous threats to the agricultural environment and public health. Therefore, it is particularly important to develop sensitive and interference-resistant deoxynivalenol analysis methods. Here, we establish a "Lollipop" particle counting immunoassay (LPCI) based on antigen-powered CRISPR-Cas12a dual signal amplification. LPCI achieves high sensitivity and accuracy through antigen-powered CRISPR-Cas dual signal amplification combined with particle counting immunoassay. This strategy not only broadens the applicability of the CRISPR-Cas system in the field of non-nucleic acid target detection; it also improves the sensitivity of particle counting immunoassay. The introduction of a polystyrene "lollipop" immunoassay carrier further enables efficiently simultaneous pre-treatment of multiple samples and overcomes complex matrix interference in real samples. The linear detection range of LPCI for deoxynivalenol was 0.1-500 ng/mL with a detection limit of 0.061 ng/mL. The platform greatly broadens the scope of the CRISPR-Cas sensor for the detection of non-nucleic acid hazards in the environment and food samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by the ubiquitin-proteasome system (UPS). Importantly, RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. We also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity, which may be exploited as a prognostic marker for COVID-19. Furthermore, RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV, suggesting that targeting RNF5 is a broad-spectrum antiviral strategy. Our findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication, which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic., (© 2023. The Author(s).)

Interferon-inducible transmembrane protein 3 (IFITM3) inhibits influenza virus infection by blocking viral membrane fusion, but the exact mechanism remains elusive. Here, we investigated the function and key region of IFITM3 in blocking influenza virus entry mediated by hemagglutinin (HA). The restriction of IFITM3 on HA-mediated viral entry was confirmed by pseudovirus harboring HA protein from H5 and H7 influenza viruses. Subcellular co-localization and immunocoprecipitation analyses revealed that IFITM3 partially co-located with the full-length HA protein and could directly interact with HA 2 subunit but not HA 1 subunit of H5 and H7 virus. Truncated analyses showed that the transmembrane domain of the IFITM3 and HA 2 subunit might play an important role in their interaction. Finally, this interaction of IFITM3 was also verified with HA 2 subunits from other subtypes of influenza A virus and influenza B virus. Overall, our data demonstrate for the first time a direct interaction between IFITM3 and influenza HA protein via the transmembrane domain, providing a new perspective for further exploring the biological significance of IFITM3 restriction on influenza virus infection or HA-mediated antagonism or escape., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Deoxynivalenol (DON) is highly toxic to the environment and human health. It is important to detect DON with ultra-high sensitivity, ease of operation, and low cost. Inspired by the excellent stability and biocompatibility of polydopamine, a universal, portable and ultra-sensitive pipet immunoassay platform was reported for DON detection based on dopamine self-polymerization (polydopamine coating and polydopamine nanoparticles). The polydopamine coating acted as an effective strategy for biomolecule immobilization on the pipet to improve the coating efficiency that significantly reduced the required concentration of biomolecules. Performing the ELISA in pipets saved nearly 67% of the antigen amount and 83% of the antibody amount, which reduced the detection cost and simplified the experimental steps. The dual signal amplification in this pipet immunoassay enabled ultra-high sensitivity. Polydopamine nanoparticles acted as the enrichment carrier of horseradish peroxidase-goat anti-mouse IgG for the first-round signal amplification, followed by the tyramine-mediated loading of streptavidin-HRP for the second-round signal amplification. The dual-enriched HRP catalyzed the color-developing substrate to achieve highly sensitive colorimetric DON detection with a limit of detection of 0.435 ng/mL., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We report a highly efficient method to construct 3-trifluoromethyl coumarins using CF 3 SO 2 Cl as the trifluoromethyl radical source with ester 3-arylpropiolates. The reaction incorporated a cascade cyclization/dearomatization/ester migration/oxidization/rearomatization process to afford various 3-trifluoromethyl coumarins under visible light irradiation in good to excellent yields.

Objective: To study the feasibility and the generalizability of the Remote fitting models of hearing AIDS from primary hospitals., Method: we comparative analyzed the speech recognition scores and satisfaction of 45 cases with traditional hearing AID fitting and with a hearing aid remote test respectively., Result: 45 cases were analyzed in each group, including traditional hearing AID fitting model and remote test, and 35 recovered in traditional fitting model group, and the recovery rate was 77.8%; Remote fitting model rehabilitation 42 cases, recovery rate was 93.3%, the difference was statistically significant (P < 0.05). In 6 weekend wear hearing AIDS, traditional fitting model of speech recognition rate increased by 19.40% on average, the average distance fitting model speech recognition rate increases by 27.47%, the average distance fitting model than traditional fitting the speech recognition rate increased significantly more (8.07%). Effect of hearing aid international questionnaire results suggest: 45 cases using traditional model fitting hearing AIDS patients, 33 cases (73.3%) satisfaction, 12 cases (26.7%) patients after use. Remote and 45 cases of using hearing AIDS fitting model, satisfied with 40 cases (88.9%), 5 cases (11.1%) patients after use., Conclusion: the curative effect and the satisfaction of remote fitting models of hearing AIDS on hearing impairment are better than that in patients with traditional fitting models. Therefore it is more worthy of clinical application especially in basic level hospitals.