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It is very important to determine mercury owing to its complex biological poisonousness that could cause various physical diseases and even death. In this study, we designed a novel coumarin-based ratiometric fluorescent probe, CR-Hg , with DL-dithiothreitol moiety as the recognition receptor to detect mercury ions (Hg2+). CR-Hg could realize the quantitative detection of Hg2+ between 0 and 1.4 μM with low detection limit (1.6 nM). Furthermore, CR-Hg could react quickly with Hg2+ in a few seconds and accompanied by color changes from pale yellow to orange. In the end, the applications of CR-Hg in the water samples, living cells and zebrafish more deeply indicated that the probe could serve as a novel promising tool for revealing mercury distribution in the environment and organisms. Image 1 • Probe CR-Hg is a colorimetric and ratiometric fluorescent probe for Hg2+. • CR-Hg could quantitatively and sensitively detect Hg2+ (DL = 1.6 nM). • CR-Hg could rapidly detect Hg2+ (within 5 s). • CR-Hg displayed prominent selectivity toward Hg2+ than other various species. • CR-Hg could be applied to determining Hg2+ in water samples, live cells and zebrafish. [ABSTRACT FROM AUTHOR]

The accurate monitoring of vital physiological parameters, exemplified by heart rate, respiratory rate, and intracranial pressure (ICP), is of paramount importance, particularly for managing severe cranial injuries. Despite the rapid development of implantable ICP sensing systems over the past decades, they still suffer from, for example, wire connection, low sensitivity, poor resolution, and the inability to monitor multiple variables simultaneously. Here, we propose an ultrasensitive multimodal biotelemetric system that amalgamates an iontronic pressure transducer with exceptional point (EP) operation for the monitoring of ICP signals. The proposed system can exhibit extraordinary performance regarding the detection of minuscule ICP fluctuation, demonstrated by the sensitivity of 115.95 kHz/mmHg and the sensing resolution down to 0.003 mmHg. Our system excels not only in the accurate quantification of ICP levels but also in distinguishing respiration and cardiac activities from ICP signals, thereby achieving the multimodal monitoring of ICP, respiratory, and heart rates within a single system. Our work may provide a pragmatic avenue for the real-time wireless monitoring of ICP and thus hold great potential to be extended to the monitoring of other vital physiological indicators., (© 2024. The Author(s).)

Background: Acute lung injury (ALI) is a serious and common complication that occurs in children with congenital heart disease after cardiopulmonary bypass (CPB) surgery, leading to higher mortality rates and poorer prognosis. Currently, there is no reliable predictive strategy for CPB-associated lung injury (CPB-ALI) in infants. Certain characteristics of the gut microbiota could potentially serve as biomarkers for predicting the development of CPB-ALI., Methods: We conducted 16S rRNA sequencing to analyze the characteristics of the intestinal microbiota in healthy controls and infants with CHD admitted to the hospital. The CHD infants were divided into CPB-ALI and non-ALI (CPB-NALI) groups based on postoperative outcomes. Bacterial functional pathway prediction analysis was performed using PIRCUSt2, and the gut microbiota composition associated with immune status was determined with heatmap. Random forest regression models and ROC curves were utilized to predict the occurrence of CPB-ALI., Results: Our study revealed significantly different microbiota compositions among three groups (CON, CPB-ALI, and CPB-NALI). The microbiota diversity was low in the CPB-ALI group with high pathogen abundance and significant decrease in Bacteroides, while the opposite was observed in the CPB-NALI group. The microbiota dysbiosis index was high in the CPB-ALI group, with its dominant microbiota significantly associated with multiple metabolic pathways. Additionally, CPB-ALI patients showed high levels of inflammatory cytokines IL-8 and HMGB1 in their serum, with high expression of IL-8 being associated with Enterobacteriaceae. Further correlation analysis showed that the differences in gut bacterial taxonomy were related to the occurrence of ALI, length of stay in the cardiac care unit, and ventilation time. It is noteworthy that Escherichia Shigella performed best in distinguishing CPB-ALI patients from non-ALI patients., Conclusions: Our study suggests that postoperative ALI patients have distinct gut microbiota upon admission compared to non-ALI patients after surgery. Dysbiosis of the gut microbiota may potentially impact the progression of ALI through metabolic pathways, quorum sensing, and the levels of inflammatory factors expressed in the serum. Escherichia Shigella represents a potential predictive factor for the occurrence of ALI in CHD infants after surgery. Acute lung injury, congenital heart disease, cardiopulmonary bypass surgery, gut microbiota, biomarker., 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, Cun, Wang, Wu, Hu, Wu, Zhu, Yang, Patel, Cai, Qi and Mo.)

In order to further improve performance of the Slime Mould Algorithm, the Enhanced Multi-Strategy Slime Mould Algorithm (EMSMA) is proposed in this paper. There are three main modifications to SMA. Firstly, a leader covariance learning strategy is proposed to replace the anisotropic search operator in SMA to ensure that the agents can evolve in a better direction during the optimization process. Secondly, the best agent is further modified with an improved non-monopoly search mechanism to boost the algorithm's exploitation and exploration capabilities. Finally, a random differential restart mechanism is developed to assist SMA in escaping from local optimality and increasing population diversity when it is stalled. The impacts of three strategies are discussed, and the performance of EMSMA is evaluated on the CEC2017 suite and CEC2022 test suite. The numerical and statistical results show that EMSMA has excellent performance on both test suites and is superior to the SMA variants such as DTSMA, ISMA, AOSMA, LSMA, ESMA, and MSMA in terms of convergence accuracy, convergence speed, and stability.

Background: Recurrent spontaneous miscarriage (RSM) is one of the complications during pregnancy. However, the pathogenesis of RSM is far from fully elucidated., Objective: Since the endocytic pathway is crucial for cellular homeostasis, our study aimed to explore the roles of endocytic recycling, especially EH domain containing 1 (EHD1), a member of the endocytic recycling compartment, in RSM., Study Design: We first investigated the expression of the endocytic pathway member EHD1 in villi from the normal and RSM groups. Then, we performed RNA sequencing and experiments in villi, HTR8 cells and BeWo cells to determine the mechanisms by which EHD1 induced RSM. Finally, placenta-specific EHD1-overexpressing mice were generated to investigate the RSM phenotype in vivo., Results: EHD1 was expressed in extravillous trophoblasts (EVTs) and syncytiotrophoblast (STB) in the villi. Compared with the control group, RSM patients expressed higher EHD1. A high level of EHD1 decreased proliferation, promoted apoptosis, and reduced the migration and invasion of HTR8 cells by activating the TGFBR1-SMAD2/3 signaling pathway. The TGFBR1 antagonist LY3200882 partially reversed the EHD1 overexpression-induced changes in the cell phenotype. Besides, a high level of EHD1 also induced abnormal syncytialization, which disturbed maternal-fetal material exchanges. In a mouse model, placenta-specific overexpression of EHD1 led to the failure of spiral artery remodeling, excessive syncytialization and miscarriage., Conclusions: Increased expression of EHD1 impaired the invasion of EVTs mediated by the TGFBR1-SMAD2/3 signaling pathway and induced abnormal syncytialization of STB, which is at least partially responsible for RSM., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Iron is an essential element in the composition of living organisms and plays a crucial role in a wide range of biological activities. The human body primarily obtains essential iron through the consumption of food. Therefore, it is vital for the health of human body to maintain iron homeostasis. The reducing character of the cellular microenvironment enables Fe 2+ to occupy a dominant position within the cell. Hence, there is an urgent need for a simple and sensitive tool that can detect a large amount of Fe 2+ in organisms. In this work, a highly specific fluorescent chemodosimeter NPCO ("NP" represents the naphthalimide fluorophore, and "CO" represents the carbamoyl oxime structure) for the detection of Fe 2+ with excellent sensitivity (LOD = 82 nM) was constructed by incorporating a novel carbamoyl oxime structure as the recognition group. NPCO can be effectively employed for the detection of Fe 2+ in food samples, living cells, and zebrafish. Furthermore, by using soybean sprouts as a model plant, the application of NPCO was expanded to detect Fe 2+ in plants. Therefore, NPCO could be used as an excellent assay tool for detecting Fe 2+ in organisms and is expected to be an important aid in exploring the mechanism of iron regulation.

Natural stilbenes have been studied extensively as a result of their complicated structures and diverse biological activities. Singlet oxygen ( 1 O 2 ), a kind of reactive oxygen species (ROS) has a strong destructive effect on food systems (especially for light-sensitive foods). Many cutting-edge scientific studies have found that some stilbenes not only have extensive quenching properties for ROS, but also can selectively quench 1 O 2 . However, the industry devoted too much energy on the development of more new stilbenes, lacking in-depth summaries and reflections on the characteristics of their basic structure and the mechanism of their extraordinary 1 O 2 quenching abilities. Therefore, we summarized the classification methods for stilbene compounds and evaluated similarities, differences and possible limitations of different classification methods. In addition, we described the role of different functional groups in stilbenes in quenching of 1 O 2 and summarized the quenching mechanism of 1 O 2 by stilbenes. By the way, the current application of stilbene compounds and their potential risks in the food industry were also mentioned in this article. The stilbenes can be used as antioxidants (especially new strategies against 1 O 2 oxidation) in food systems to improve the shelf life. At this stage, it is necessary to develop more effective and safe food antioxidant stilbenes based on their quenching mechanism.

Staphylococcus aureus is one of the most prevalent bacteria found in acute wounds. S. aureus produces many virulence factors and extracellular enzymes that contribute to bacterial survival, dissemination, and pathogenicity. Lipase GehB is a glycerol ester hydrolase that hydrolyzes triglycerides to facilitate the evasion of S. aureus from host immune recognition. However, the role and mechanism of lipase GehB in skin acute wound healing after S. aureus infection remain unclear. In this study, we found that the gehB gene deletion mutant (USA300ΔgehB) stimulated significantly higher levels of pro-inflammatory cytokines in RAW264.7 and Toll-like receptor 2 (TLR2)-transfected HEK293 cells than the wild-type USA300 strain did. Recombinant GehB-His treated lipoprotein (Lpp) reduced stimulation of TLR2-dependent TNF-α production by RAW264.7 macrophages. GehB delayed the skin acute wound healing in BALB/c mice infected with S. aureus, while wound healing was similar in C57BL/6 TLR2 -/- mice infected with either wild-type USA300 or USA300ΔgehB. In BALB/c mice, we also observed more bacterial survival, less leukocyte recruitment, lower IL-8 production, and adipocyte differentiation in USA300-infected skin acute wound tissues than those in USA300ΔgehB-challenged ones. Our data indicated that GehB inactivates lipoproteins to shield S. aureus from innate immune killing, resulting in delayed the healing of skin acute wounds infected with S. aureus., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD)., Method: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiece were reconstructed from the MR images. CFD simulations coupled with discrete phase modelling were conducted. Inhaled polydisperse particles under two different transient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and 60 L/min were investigated. The effect of inhaler mouthpiece resistance was modelled as a porous medium by varying the initial resistance (Ri) and viscous resistance (Rv). Three resistance values, 0.02 kPa 0.5 minL -1 , 0.035 kPa 0.5 minL -1 and 0.05 kPa 0.5 minL -1 , were simulated. The inhaler outlet velocity was set to be consistent across all models for both flow rate conditions to enable a meaningful comparison of models with different inhaler resistances., Result: The results from this study demonstrate that investigating the effect of inhaler resistance by solely relying on the USP throat model may yield misleading results. For the geometrically realistic oropharyngeal model, both the pressure and kinetic energy profiles at the mid-sagittal plane of the airway change dramatically when connected to a higher-resistance inhaler. In addition, the geometrically realistic oropharyngeal model appears to have a resistance threshold. When this threshold is surpassed, significant changes in flow dynamics become evident, which is not observed in the USP throat model. Furthermore, this study also reveals that the impact of inhaler resistance in a geometrically realistic throat model extends beyond the oral cavity and affects particle deposition downstream of the oral cavity, including the oropharynx region., Conclusion: Results from this study suggest that key mechanisms underpinning the working principles of inhaler resistance are intricately connected to their complex interaction with the pharynx geometry, which affects the local pressure, local variation in velocity and kinetic energy profile in the airway., Competing Interests: Declaration of competing interest All authors report no potential competing interests. The content of the manuscript has not been published or submitted for publication elsewhere, and all authors have approved the manuscript for the submission to Computers in Biology and Medicine., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Considering the United Nations' Sustainable Development Goals (SDGs) and the need for a balanced spatial distribution of urban medical resources capable of perspective of hierarchical diagnosis and treatment, i.e. providing continuous and accessible medical services during potential public health emergencies, we assessed accessibility and service capacity of the three hospital levels in Beijing. Using geographical information systems (GIS) and the two-step floating catchment area method with the street as research unit, we found that there is an over-supply of medical resources in the centre of the city with weaker support in the peripheral areas as manifested by less supply in relation to popular demand of medical services. The spatial distribution of hospitals at all levels and their resources was found to be uneven: 82.4% of the residents can reach a tertiary hospital (a hospital offering advanced specialized medical and health services to multiple regions) within a 15-minute drive; 50.6% can reach a secondary hospital (a hospital offering comprehensive medical and health services to various communities) within a 10-minute drive; and 77.6% can reach a primary hospital (a hospital directly delivering prevention, medical treatment, healthcare, and rehabilitation services to the community of a certain population) within a 15- minute walk. It was noted that the supply/demand balance of medical resources in the tertiary hospitals decreases from the centre to the periphery, while the secondary hospitals show a dual-centre pattern and the primary hospitals a more uneven distribution, with oversupply in the East and the opposite in the Centre. The results of the study provide supplementary decision support for improving the hierarchical diagnosis and treatment system and accelerate the overall deployment of medical resources.

Background: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy., Methods: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR., Results: We screened 808 DEGs (log2 fold change (FC) > 1 or <  - 1, p < 0.05), 4 DETFs (log2FC > 0.7 or <  - 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or <  - 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or <  - 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review., Conclusions: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia., (© 2023. The Author(s).)

The induction of seed dormancy and its release involve a finely regulated genetic program controlled by various environmental and developmental cues that are critical for plant survival and population expansion. Light plays a key role in seed dormancy and germination, but the molecular mechanisms underlying the control of dormancy are unclear. In the present study, high-resolution temporal RNA-seq in Arabidopsis identified WOX11 as encoding a hub transcription factor during the seed dormancy induction and release stages. This gene might have evolved from gymnosperms and expanded in angiosperms with highly conserved expression patterns in seeds. WOX11 and its homolog WOX12 were highly expressed from 2 d after pollination, and mRNA abundance was greatly increased during the seed dormancy induction and release stages. Further, we found that WOX11 plays a role in the regulation of seed dormancy downstream of phytochrome B (PHYB)-mediated red-light signaling during the induction stage, indicating that WOX11/12 are newly identified components of red-light signaling transduction. Taken together, our results suggest that WOX11/12-mediated PHYB signaling regulates seed dormancy in Arabidopsis, and provide insights into the developmental regulation and evolutionary adaptation of plants to changes in the light environment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aims to investigate peroxiredoxin 3 (PRDX3) expression in gastric cancer tissue and its effects on cisplatin resistance in gastric cancer cells and its possible mechanism., Methods: PRDX3 expression in human gastric cancer tissue microarrays was detected via immunohistochemistry. The PRDX3 small interfering RNA (siPRDX3 group) and the negative control siNC (siNC group) were transfected into AGS and MKN-74 cell lines, respectively, whereas a blank control group was set up. Each group was treated with different cisplatin concentrations (0, 5, 10, 15, 20, 25, and 30 μg/ml), and the half-inhibitory concentration (IC 50 ) of each group of the two cell lines was calculated using the CCK8 assay. The corresponding IC 50 concentration of the siPRDX3 group in the two cell lines was used to treat cells of each group. Flow cytometry was used to detect cell apoptosis, and Western blotting was used to detect the expression levels of cleaved caspase-3 and Bax in each group., Results: PRDX3 was overexpressed in gastric adenocarcinoma tissue compared with adjacent noncancer tissue (P = 0.0053). After cisplatin treatment, the IC 50 in the siPRDX3 group of AGS cells (5.91 ± 0.18 μg/ml) and the siPRDX3 group of MKN-74 cells (3.48 ± 0.30 μg/ml) was significantly lower than in the corresponding siNC groups (10.01 ± 0.99 and 6.39 ± 0.70 μg/ml; P = 0.0022 and 0.0027, respectively). AGS cells (38.81% ± 1.69%) and MKN-74 cells (25.03% ± 2.80%) in the siPRDX3 group showed significantly higher apoptosis rates than in the corresponding siNC groups (23.17% ± 1.43% and 16.7% ± 1.39%; P = 0.0003 and 0.0099, respectively). The expression levels of cleaved caspase-3 and Bax were significantly higher in the siPRDX3 group of both cell lines than in the siNC group (P < 0.0001)., Conclusion: PRDX3 increases the gastric cancer cell resistance to cisplatin by reducing apoptosis and thus may serve as a target to overcome cisplatin resistance., Competing Interests: None

Embryo adhesion is a very important step in the embryo implantation process. Homeobox A10 (HOXA10), a key transcriptional factor of endometrial receptivity, is indispensable for embryo adhesion. However, how to control the activation status of HOXA10 remains elusive. Here, we found that Mitogen-activated protein kinase kinase kinase 4 (MEKK4) was associated with HOXA10 and directly phosphorylated HOXA10 at threonine 362. This MEKK4-mediated phosphorylation enhanced HOXA10-mediated transcriptional responses and adhesion between the embryo and endometrial epithelium. Specific deletion or kinase inactivation of MEKK4 in endometrial epithelial cells attenuates adhesion between embryo and epithelium. Therefore, the identification of MEKK4 as a novel physiological positive regulator of HOXA10 activation provides mechanistic insights to improve embryo implantation success. Moreover, when Thr362 was mutated to alanine (T362A) to mimic its dephosphorylation, the protein stability and transcriptional regulation of HOXA10 were decreased. In addition, HOXA10 -promoted embryo adhesion was weakened after the mutation of Thr362, suggesting that the phosphorylation of HOXA10 at this site may be a new indicator for evaluating endometrial receptivity and judging the 'implantation window'., (© 2022. The Author(s).)

Decidualization is a prerequisite for successful embryo implantation, in which elongated fibroblast-like endometrial stromal cells differentiate into more rounded decidual cells. Accumulating evidence has stressed the important role of the defective eutopic endometrium in infertility in endometriosis patients. However, the role of arginine methylation in the process of physiological decidualization and pathological decidualization defects is not clear. Here, we observed that the expression level of PRMT5, the main type II PRMT, was decreased in the endometrium of endometriosis patients, predominantly in stromal cells. Compared with the undecidualized state, PRMT5 was increased in the stromal cells of normal secretory endometrium in humans and in the decidua of normal pregnant mice or mice with artificially induced decidualization. The inhibition of PRMT5 resulted in a significant decrease in uterine weight and decidualization-related regulator expression, including FOXO1, HOXA10 and WNT4, in mice and IGFBP1 and prolactin levels in human endometrial stromal cells. Transcriptome analysis showed that decreased PRMT5 activity led to NF-κB signaling activation by inducing p65 translocation to the nucleus, which was also observed in endometriosis patients. Finally, overexpression of PRMT5 rescued the defective expression of IGFBP1 and prolactin in primary endometrial stromal cells from endometriosis patients. Our results indicate that promotion of PRMT5 may provide novel therapeutic strategies for the treatment of decidualization defects in infertile women, such as those with endometriosis., (© 2022. The Author(s).)

Background: Gestational trophoblastic disease (GTD) usually affects young women of childbearing age. After treatment for GTD, 86% of women wish to achieve pregnancy. On account of the impacts of GTD and treatments as well as patient anxiety, large numbers of couples turn to assisted reproductive technology (ART), especially in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). But few studies have investigated whether a history of GTD affects the outcomes of IVF/ICSI in secondary infertile patients and how it occurs. We investigate whether a history of GTD affects the IVF/ICSI outcomes and the live birth rates in women with secondary infertility., Methods: This retrospective cohort study enrolled 176 women with secondary infertility who underwent IVF/ICSI treatment at the reproductive medical center of Nanjing Drum Tower Hospital from January 1, 2016, to December 31, 2020. Participants were divided into the GTD group (44 women with GTD history) and control group (132 women without GTD history matched from 8318 secondary infertile women). The control group and the study group were matched at a ratio of 3:1 according to patient age, infertility duration, number of cycles and body mass index (BMI). We assessed retrieved oocytes and high-grade embryos, biochemical pregnancy, miscarriage, ectopic pregnancy, gestational age at delivery, delivery mode and live birth rates., Result(s): We found a significantly reduced live-birth rate (34.1% vs 66.7%) associated with IVF/ICSI cycles in patients with a GTD history compared to those without a GTD history. The biochemical pregnancy and miscarriage rates of the GTD group were slightly higher than those of the control group. In addition, there was a difference in gestational age at delivery between the GTD and control groups (p < 0.001) but no differences in the mode of delivery (p = 0.267). Furthermore, the number of abandoned embryos in the GTD group was greater than that in the control group (p = 0.018), and the number of good-quality embryos was less than that in the control group (p = 0.019). The endometrial thickness was thinner (p < 0.001) in the GTD group. Immunohistochemistry (IHC) showed abnormal endometrial receptivity in the GTD group., Conclusion(s): The GTD history of patients undergoing IVF/ICSI cycles had an impact on the live-birth rate and gestational age at delivery, which might result from the thinner endometrium and abnormal endometrial receptivity before embryo transfer., (© 2022. The Author(s).)

Introduction: Allergic contact dermatitis (ACD) constitutes a considerable part of allergic morbidity among the population, although its actual prevalence is unknown as it is often not properly diagnosed., Aim: To determine the incidence of ACD compared to other allergic dermatoses in patients from the Russian Federation and the People's Republic of China, as well as analyse immunological parameters of ACD., Material and Methods: The study enrolled a total of 248 patients aged 17-63 years divided into two groups representing the population of the Russian Federation (122 patients) and the People's Republic of China (126 patients). The total male and female ratio in both groups was 183 (74%) to 58 (26%)., Results: The frequency of ACD incidence among other allergic dermatoses in the group of patients from the Russian Federation was 26.2%, while that in the group of patients representing the population of the PRC amounted to 22.2%. In the group of patients from the Russian Federation, positive reactions to allergens were most often observed for thiomersal (29.8%), nickel sulfate (25.2%), and a mixture of carbamates (20.7%), and in the group of patients from China, for nickel sulfate (30.7%), thiomersal (26.4%), and a mixture of carbamates (23.8%)., Conclusions: The incidence rate of ACD among patients with allergic dermatoses is about a quarter of cases in groups from both regions. The increased expression of defensin and IFN-γ genes can be considered as a marker of inflammation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia Sp. z o. o.)

As a eukaryotic organelle, the Golgi apparatus plays an essential role in various physiological activities such as stress response. The Golgi stress response is an important physiological process of conferring cytoprotection by regulating the synthesis and metabolism of bioactive molecules. Therefore, the development of new suitable in situ analytical techniques for monitoring related small molecular substances in the stress reaction of the Golgi apparatus is very helpful for further study of the regulatory mechanism of the Golgi apparatus. Recent studies have shown that endogenous hydrogen sulfide (H 2 S) also possesses crucial bioregulatory and protective performances in the stress response. Therefore, the high-fidelity in situ mapping of H 2 S production under the Golgi stress response plays an important role not only in revealing cytoprotection functions of H 2 S in the stress response but also in further understanding the regulatory mechanism of the Golgi stress response. In this work, we designed a simple Golgi-targetable H 2 S fluorescent probe ( Gol-H 2 S ) that responds accurately and sensitively to H 2 S in the Golgi apparatus of living cells and zebrafish. On the basis of its superior bioimaging performances, probe Gol-H 2 S was successfully applied to the in situ visualization of H 2 S production under the Golgi stress response elicited by monensin, a specific-Golgi stressor. The related process of the Golgi stress response was validated by stimulation and inhibition experiments. These findings fully demonstrate that H 2 S is an alternative biomarker of the Golgi stress response. Moreover, probe Gol-H 2 S can also be used as a potential tool for disclosing the detailed H 2 S-cytoprotection mechanisms under the regulation of the Golgi stress response in related diseases.

Oncolytic viruses are an excellent platform for developing effective strategies in cancer immunotherapy. Several challenges remain in the use of viro-immunotherapy for cancer, such as the lack of costimulatory signals and negative regulation of immune checkpoints. In this study, we designed a novel adenovirus expressing a soluble fusion protein, programmed cell death protein 1 (PD-1)/CD137L, which contains the extracellular domains of PD-1 and CD137L at each terminus (Ad5-PC). Ad5-PC preserved the costimulatory activity of CD137L and facilitated the persistence of activated CD8 + T cells. Ad5-PC induced strikingly increased antitumor activity in both ascitic and subcutaneous hepatocellular carcinoma (HCC) tumor models, with 70% and 60% long-term cure rates, respectively. The improved antitumor effect of Ad5-PC was attributed to the sustained high-level lymphocyte activation and interferon (IFN)-γ production in the tumor microenvironment, and was essentially dependent on CD8 + T cells rather than natural killer (NK) cells. Moreover, Ad5-huPC-expressing human soluble PD-1/CD137L fusion protein was effective in suppressing tumor growth and improving survival in a humanized mouse model. We confirmed that Ad5-PC induced tumor-specific and systematic protection against tumor rechallenges at both in situ and distant sites. Thus, Ad5-PC harnesses several distinct functions to efficiently overcome several major hurdles of viro-immunotherapy., (Copyright © 2019 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the effectiveness of proximal femoral nail antirotation (PFNA) combined with mini plate for reconstruction of lateral femoral wall in the treatment of type AO/Orthopaedic Trauma Association (AO/OTA) type 31-A3 intertrochanteric fracture., Methods: The clinical data of 70 elderly patients with AO/OTA type 31-A3 intertrochanteric fracture treated between January 2013 and January 2018 were retrospectively analyzed. They were divided into group A (PFNA alone, 35 cases) and group B (PFNA combined with mini plate reconstruction of lateral femoral wall, 35 cases). There was no significant difference in the general data of gender, age, side, cause of injury, time from injury to operation between the two groups ( P >0.05). The operation time, intraoperative blood loss, fracture healing time, postoperative complications, and the tip apex distance (TAD) at 2 months after operation were recorded and compared between the two groups. Harris hip score was used to evaluate the function at 12 months after operation., Results: Both groups were followed up 9-21 months, with an average of 16.6 months. The operation time and intraoperative blood loss in group A were significantly less than those in group B ( P <0.05); there was no significant difference in TAD between the two groups at 2 months after operation ( t =0.096, P =0.462). There were 5 complications (14.3%) occurred in group A, including 2 cases of blade perforating from the hip joint, 2 cases of screw back out, and 1 case of bone nonunion; only 1 case (2.9%) in group B had screw back out after operation; there was no significant difference in the incidence of complications between the two groups ( χ 2 =2.917, P =0.088). All the fracture healed in group B, and 1 patient in group A suffered bone nonunion and eventually main nail fracture. The healing time of fracture in group A [(15.6±2.7) weeks] was significantly longer than that in group B [(12.5±2.5) weeks], showing significant difference ( t =2.064, P =0.023). At 12 months after operation, according to Harris score, the results were excellent in 5 cases, good in 9 cases, fair in 13 cases, and poor in 8 cases in group A, the qualified rate (Harris score>70) was 77.14%; and the results were excellent in 7 cases, good in 11 cases, fair in 16 cases, and poor in 1 case in group B, the qualified rate was 97.14%; there was significant difference in the qualified rate between the two groups ( χ 2 =6.248, P =0.012)., Conclusion: Compared with PFNA alone, the treatment of AO/OTA type 31-A3 intertrochanteric fracture with PFNA combined with mini plate reconstruction of lateral femoral wall can significantly reduce postoperative complications, promote fracture healing, and improve functional recovery of patients after operation.

Tendinopathy is a critical clinical problem as it is often asymptomatic at onset and during development, and is only recognized upon rupture of the tendon. It is common among recreational and competitive athletes. The present study sought to examine the molecular mechanism of the progression of tendinopathy by screening out differentially expressed genes (DEGs) and investigating their functions. In addition, the present study aimed to identify the small molecules, which exhibit potential effects, which could be utilized for the treatment of tendinopathy. The gene expression profile of tendinopathy, GSE26051 was downloaded from the Gene Expression Omnibus database, which included 23 control samples and 18 samples of tendinopathy. The DEGs were identified using the Limma package in the R programming language, and gene ontology and pathway enrichment analysis were performed. In addition, the potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify the potential small molecule drugs. A total of 318 genes were filtered as DEGs between diseased samples and normal control tendons. Additionally, genes, including laminin, α4, platelet‑derived growth factor α, laminin γ1 and Src homology 2 transforming protein 1 may induce tendinopathy through the focal adhesion pathway. Furthermore, the transcription factor, lymphoid enhancer‑binding factor 1 and its target genes, pantothenate kinase 2 and G protein‑coupled receptor kinase 5 were identified. The most significant microRNA, miR‑499, was screened and was found to regulate specific genes, including CUGBP2 and MYB. Additionally, the small molecules, Prestwick‑1082 and viomycin were identified to have the potential to repair disordered metabolic pathways and furthermore to remedy tendinopathy. The results of the present study assessed the mechanism of tendinopathy and screened small molecule drugs as potential treatments for this condition. In addition, the present findings have the potential for use in a clinical setting for the treatment of tendinopathy in the future.