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Yang Chen,1 Hui-Yi Li,1 Jian-Shu Liu,1 Dao-long Jiang,1 Hao-nan Zheng,2 Xue-Song Dong1 1Department of Emergency, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2No.105 Phase, The First Clinical College of China Medical University, Shenyang, 110001, People’s Republic of ChinaCorrespondence: Xue-Song Dong, Department of Emergency, The First Hospital of China Medical University, No. 155 of Nanjing North Street, Heping District, Shenyang, 110001, People’s Republic of China, Tel +86 024-26111099 ; +86 024-83282011, Email dongxunsongdxs0@126.comBackground: We established a diquat-induced human kidney-2 cells (HK-2 cells) apoptosis model in this study to identify differentially expressed microRNAs (miRNAs) and signaling pathways involved in diquat poisoning via gene sequencing and bioinformatics analysis and explored the related therapeutic benefits.Methods: The effects of diquat on the viability and apoptosis of HK-2 cells were explored using the CCK-8 and Annexin V-FITC/PI double staining methods. Total RNAs were extracted using the TRizol method and detected by Illumina HiSeq 2500. Bioinformatics analysis was performed to explore differentially expressed (DE) miRNAs, their enriched biological processes, pathways, and potential target genes. The RT-qPCR method was used to verify the reliability of the results.Results: Diquat led to HK-2 cell injury and apoptosis played an important role, hence an HK-2 cell apoptosis model in diquat poisoning was established. Thirty-six DE miRNAs were screened in diquat-treated HK-2 cells. The enriched biological process terms were mainly cell growth, regulation of apoptotic signaling pathway, extrinsic apoptotic signaling pathway, and Ras protein signal transduction. The enriched cellular components were mainly cell-cell junction, cell-substrate junction, ubiquitin ligase complex, and protein kinase complex. The enriched molecular functions were mainly Ras GTPase binding, ubiquitin-like protein transferase activity, DNA-binding transcription factor binding, ubiquitin-protein transferase activity, nucleoside-triphosphatase regulator activity, transcription coactivator activity, and ubiquitin-like protein ligase binding. Signaling pathways such as MAPK, FoxO, Ras, PIK3-Akt, and Wnt were also enriched.Conclusion: These findings aid in understanding the mechanisms of diquat poisoning and the related pathways, where DE miRNAs serve as targets for gene therapy.Keywords: apoptosis, biological processes, diquat, HK-2 cells, microRNA

Abstract: Restoration of mesenteric lymphatic microcirculation is crucial for alleviating severe hemorrhagic shock-induced death. Exercise preconditioning (EP) enhances adaptability and resistance to injury and disease. The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the energy and information exchange between the two organelles. Therefore, we hypothesized that EP ameliorates mesenteric lymphatic contractility through MAM in rats following hemorrhagic shock, aiming to confirm that EP enhances resistance to hemorrhagic shock and further popularizes the idea that exercise is beneficial for health. To test this hypothesis, we observed the effects of EP for 4 weeks on survival time and mesenteric lymphatic contractility in conscious rats following hemorrhagic shock and further explored the effects of MAM agonists and inhibitors. The results showed that EP prolonged the survival time and improved the mesenteric lymphatic contractility and reactivity in vivo and in vitro in rats underwent hemorrhagic shock, ameliorated the MAM ultrastructure in lymphatic smooth muscle cells (LSMCs) and reduced the voltage-dependent anion channel 1 (VDAC1, a vital protein of MAM) and IP3R1 expressions in mesenteric lymphatic tissue. Importantly, treatment with 2-APB (IP3R1 inhibitor) or VBIT-12 (VDAC1 inhibitor) prolonged the survival time, improved mesenteric lymphatic contractility in vivo , ameliorated the MAM ultrastructure injury, and decreased the IP3R1 or VDAC1 expressions in LSMCs in rats following hemorrhagic shock. In contrast, the administration of drinking water containing CdCl 2 (IP3R1 activator) abolished the beneficial effect of EP on hemorrhagic shock. Taken together, the protective effect of EP on lymphatic contractility following hemorrhagic shock was achieved by improving MAM in LSMCs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1)., Methods: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a -/- ) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons., Results: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx., Conclusions: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization., Significance Statement: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission., (© 2024 European Pain Federation ‐ EFIC ®.)

Aim: To explore the association between metabolic parameters evaluated by integrated 2-[ 18 F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) and the expression of immune biomarkers in the tumour microenvironment in lung adenocarcinoma., Materials and Methods: This study included 134 patients. Metabolic parameters were obtained by PET/CT. Immunohistochemistry analysis was used for FOXP3-TILs (transcription factor forkhead box protein 3 tumour-infiltrating lymphocytes), CD8-TILs, CD4-TILs, CD68-TAMs (tumour-associated macrophages) and galectin-1 (Gal-1) tumour expression., Results: There were significant positive associations between FDG PET metabolic parameters and the median percentage of immune reactive areas (IRA%) covered by FOXP3-TILs and CD68-TAMs. Negative associations with the median IRA% covered by CD4-TILs and CD8-TILs were observed: maximal standardised uptake value (SUV max ), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and IRA% for FOXP3-TILs (rho = 0.437, 0.400, 0.414; p<0.0001 for all parameters); SUV max , MTV, TLG, and IRA% for CD68-TAMs (rho = 0.356, 0.355, 0.354; p<0.0001 for all parameters); SUV max , MTV, TLG, and IRA% for CD4-TILs (rho = -0.164, -0.190, -0.191; p=0.059, 0.028, 0.027, respectively); SUV max , MTV, TLG, and IRA% for CD8-TILs (rho = -0.305, -0.316, -0.322; p<0.0001 for all parameters). There were significant positive associations between tumour Gal-1 expression and the median IRA% covered by FOXP3-TILs and CD68-TAMs (rho = 0.379; p<0.0001; rho = 0.370; p<0.0001, respectively), and a significant negative association with the median IRA% covered by CD8-TILs (rho = -0.347; p<0.0001) was observed. Tumour stage (p=0.008), Gal-1 expression (p=0.008), and median IRA% covered by CD8-TILs (p=0.054) were independent risk factors for overall survival., Conclusion: FDG PET may facilitate a comprehensive evaluation of the tumour microenvironment and predict response to immunotherapy., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To investigate the value of anteroposterior-to-transverse ratio (ATR) and the effect on features of nodules in ultrasound (US) diagnosis of thyroid nodules in different locations.  Methods: The nodules were divided into three groups according to the different nodule location: isthmus group; upper and lower poles of bilobed thyroid group; and the middle of the bilobed thyroid group. The diameters of the nodules were recorded, and ATR of the nodule was calculated on the transverse and longitudinal sections. The transverse and the longitudinal sections of ATR of thyroid nodules in different groups were compared.  Result: The transverse section of ATR was significantly different among the three groups (p = 0.001). In addition, there are significant differences in many US features among three groups, including nodule composition, thyroid parenchyma, morphology, echogenicity, shape, calcifications, vascularity, nodule ACR TI-RADS and histopathologic (all p < 0.05). In the group of upper and lower poles of bilobed thyroid, significant difference was found between the transverse and the longitudinal section of ATR (p = 0.019). The cut-off values of transverse section and longitudinal section of ATR were 0.967 and 0.750, respectively.  Conclusion: The transverse section of ATR at different location of thyroid may be a predictor for malignancy with clinical diagnostic significance.

Somatostatin-positive (SOM + ) neurons have been proposed as one of the key populations of excitatory interneurons in the spinal dorsal horn involved in mechanical pain. However, the molecular mechanism for their role in pain modulation remains unknown. Here, we showed that the T-type calcium channel Cav3.2 was highly expressed in spinal SOM + interneurons. Colocalization of Cacna1h (which codes for Cav3.2) and SOM tdTomato was observed in the in situ hybridization studies. Fluorescence-activated cell sorting of SOM tdTomato cells in spinal dorsal horn also proved a high expression of Cacna1h in SOM + neurons. Behaviorally, virus-mediated knockdown of Cacna1h in spinal SOM + neurons reduced the sensitivity to light touch and responsiveness to noxious mechanical stimuli in naïve mice. Furthermore, knockdown of Cacna1h in spinal SOM + neurons attenuated thermal hyperalgesia and dynamic allodynia in the complete Freund's adjuvant-induced inflammatory pain model, and reduced both dynamic and static allodynia in a neuropathic pain model of spared nerve injury. Mechanistically, a decrease in the percentage of neurons with Aβ-eEPSCs and Aβ-eAPs in superficial dorsal horn was observed after Cacna1h knockdown in spinal SOM + neurons. Altogether, our results proved a crucial role of Cav3.2 in spinal SOM + neurons in mechanosensation under basal conditions and in mechanical allodynia under pathological pain conditions. This work reveals a molecular basis for SOM + neurons in transmitting mechanical pain and shows a functional role of Cav3.2 in tactile and pain processing at the level of spinal cord in addition to its well-established peripheral role., 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 © 2022 Zhi, Cao, Su, Gao, Zheng, Jiang, Su, Liu, Wang, Zhang and Zhang.)

Pulmonary barotrauma is a kind of disease caused by the injury of lung tissue or blood vessel when the gas pressure of lung is too high or too lower than the external pressure of the body, which causes the air to enter the blood vessel and adjacent tissue. It could be happened in the escape of the divers with the light diving equipment or the sailors from submarine. Generally, the decompression chamber was used to treating the disease, and the minimum air pressure of 0.5 MPa recompression therapeutic schedule was used to selecting. In November 2019, a patient with pulmonary barotrauma combined with cerebral arterial gas embolism caused by improper underwater escape with light diving equipment was admitted to the General Hospital of Eastern War Zone. He was treated with 0.12 MPa oxygen inhalation recompression scheme in the oxygen chamber pressurized with air. 7 days later, the patient recovered and discharged.

Objective: To discuss the new idea of on-the-spot recompression treatment and multidisciplinary treatment (MDT) for patients with unstable vital signs of type II decompression sickness. To provide reference for the nearby treatment of patients with critical decompression sickness. Methods: The clinical data of a case of a multi-disciplinary collaborative treatment of type II decompression sickness complicated with multiple organ dysfunction syndrome (MODS) admitted to a third-class A hospital in January 2020 were analyzed and summarized. Results: The patient suffered from consciousness disturbance and shock after 3 min of diver's blow-up out of the water. CT examination showed gas accumulation in the systemic multi-organ venous system, and laboratory examination suggested MODS. The oxygen inhalation regimen was given in the session of recompression treatmen by 0.12-0.18 MPa. Intravenous fluid was the total of 8900 ml in the session, and the total recompression treatment time was 9 h 45 min. The patient was still in unconscious when he finished the session. CT re-examination confirmed the elimination of venous bubbles, and laboratory examination indicated multiple organ failure (MOF) . The patient was given comprehensive supporting treatment by mechanical assisted breathing and following by continuons renal replacement therapy (CRRT) and extrocorporeal membrane oxygenation (ECMO) in the intensive care unit, and was discharged after 32 d of hospitalization. Conclusion: Critical decompression sickness patients with unstable vital signs are taken to a local general hospital with hyperbaric oxygen chamber and intensive care unit. The successful treatment can be achieved by organizing diving medicine, hyperbaric oxygen medicine and critical medical personnel for MDT.

Objective: To investigate a new noninvasive method for calculating left ventricular diastolic time constant (Tau) through a continuous-wave aortic regurgitation Doppler spectrum., Methods: According to ultrasound guidance, twenty-four animal models (beagles) of aortic regurgitation and acute ischemic left ventricular diastolic dysfunction were created. The left ventricular diastolic function was manipulated with dobutamine or esmolol and fifty-nine hemodynamic stages were achieved. Raw audio signals of the continuous-wave Doppler spectra were collected, and new aortic regurgitation Doppler spectra were built after reprocessing by a personal computer. The updating time of the spectral line was 0.3 ms. The new Doppler spectra contour line was automated using MATLAB (MATrix LABoratory, MathWorks, Natick, MA, USA), and two time intervals, (t2-t1) and (t3-t1) were measured on the ascending branch of the aortic regurgitation Doppler spectrum. Then, the two time intervals were substituted into Bai's equations, and Doppler-derived Tau (Tau-D) was resolved and compared with catheter-derived Tau (Tau-c)., Results: There is no significant difference between Tau-D and Tau-c (45.95 ± 16.90 ms and 46.81 ± 17.31 ms, respectively; P > 0.05). Correlation analysis between Tau-c and Tau-D suggested a strong positive relationship ( r = 0.97, P = 0.000). A Bland-Altman plot of Tau-c and Tau-D revealed fair agreement., Conclusions: This new calculation method is simple, convenient, and shows a strong positive relationship and fair agreement with the catheter method., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Objective: This study was made to investigate and evaluate the safety and carcinogenicity of nitenpyram (NIT) in rats., Materials and Methods: A totally 50 male and 50 female SD rats were treated with NIT at 0, 800, 2400, and 7200 ppm, respectively, for 104 w. The growth, clinical signs, and survival rates, as well as the body and organ weights of these animals, were analyzed. Histopathological examination was also performed., Results: Compared with the control group, survival rates at 104 w were significantly decreased in the 7200 ppm dose group, for both the male and female animals. The occurrence of esophageal squamous papilloma (ESP) was significantly increased in the treated animals. The occurrences of ESP for the 0, 800, 2400, and 7200 ppm NIT treatment groups were 0/39, 0/39, 3/35, and 9/27 for the male animals, and 0/43, 0/43, 6/49, and 12/33 for the female animals, respectively. For pre-neoplastic lesion of ESP, the occurrences of esophageal squamous hyperplasia for the 0, 800, 2400 and 7200 ppm NIT treatment groups were 0/39, 1/39, 10/35, and 9/27 for the male animals, and 0/43, 2/43, 15/49, and 17/33 for the female animals, respectively. The basal cell hyperplasia from mild to severe degrees was observed in the treatment groups., Conclusions: NIT exhibits carcinogenicity of ESP in the male and female rats after the two-year treatment.

Sugar amino acids (SAAs), as biologically interesting structures bearing both amino and carboxylic acid functional groups represent an important class of multifunctional building blocks. In this study, we develop an easy access to novel SAAs in only three steps starting from nitro compounds in high yields in analytically pure form, easily available by ceric (IV) mediated radical additions. Such novel SAAs have been applied in the assembly of total nine carbopeptoids with the form of linear homo- and heterooligomers for the structural investigations employing circular dichroism (CD) spectroscopy, which suggest that the carbopeptoids emerge a well-extended, left (or right)-handed conformation similar to polyproline II (PPII) helices. NMR studies also clearly demonstrated the presence of ordered secondary structural elements. 2D-ROESY spectra were acquired to identify i+1 NH ↔  i C 1 H, i C 2 H correlations which support the conformational analysis of tetramers by CD spectroscopy. These findings provide interesting information of SAAs and their oligomers as potential scaffolds for discovering new drugs and materials.

Objective: To investigate the correlation between Young's modulus of the thyroid tissue measured by in shear wave elastography (SWE) and the clinical manifestations of Hashimoto's thyroiditis in different stages., Methods: A total of 104 patients with the clinical diagnosis of Hashimoto's thyroiditis were enrolled in this study, including 26 with hyperthyroidism, 29 with normal thyroid function, 27 with subclinical hypothyroidism, 22 with clinical hypothyroidism, with 50 healthy volunteers serving as the healthy control group. All the subjects underwent SWE to obtain the Young's modulus value of the thyroid tissue. Univariate analysis of variance was used to compare the Young's modulus among the groups, and Pearson correlation analysis was used to analyze the correlation between the Young's modulus of the thyroid tissue and serum levels of thyroid microsomal antibody (TMAb) and thyroid globulin antibody (TGAb)., Results: In the 4 groups of patients, the Young's modulus increased significantly in the order of hyperthyroidism group, normal thyroid function group, subclinical hypothyroidism group and clinical hypothyroidism group (F=60.983, P<0.01). The Young's modulus was significantly lower in hyperthyroidism group than in the other 3 groups (P<0.05), and was significantly lower in normal thyroid function group than in subclinical hypothyroidism group and clinical hypothyroidism group (P<0.05)., Conclusion: The Young's modulus of the thyroid tissue measured by shear wave elastography is related with the clinical manifestations of Hashimoto's thyroiditis in different stages, but the relevance needs to be further confirmed by multi-center, randomized, controlled studies involving a larger sample size.

The long single-stranded RNAs produced from Rolling Circle Transcription (RCT) were used as scaffolds to be folded with a few short DNA staples into RNA-DNA hybrid nanowires.

Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, commonly known as St. John's wort. Hypericin has attracted a growing attention of the pharmaceutical industry because of its potential application to various therapies, including the treatment of depression and remarkable antiviral and photodynamic activities, hyp-1 gene encodes for phenolic coupling protein which catalyzes in vitro direct and specific conversion of emodin to hypericin which, however, has not formed common opinion so far. Six pairs of primers specific to hyp-1 gene were synthesized. The rapid cloning of hyp-1 gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pET32ahyp containing hyp-1 gene was constructed and was transformed into E. coli to induce heterologous expression. SDS-PAGE and Western blot results showed the recombinant Hyp-1 protein was expressed successfully in E. coli. The soluble fraction was used to test the function of the recombinant Hyp-1. Hypericin was detected by LC-MS/MS with emodin as a substrate under in vitro conditions. The above results corroborated the Hyp-1 function, a confusing question, which lay a material foundation for the synthesis of hypericin by synthetic biotechnology.

Two surface chemistry approaches were realized to complete click reactions at covalently grafted polymer brushes of poly(poly(ethylene glycol) monomethacrylate) on a planar silicon surface (Si-g-P(PEGMAOH)). On one hand, the hydroxyls from Si-g-P(PEGMA-OH) brushes can be replaced by chlorines of thionyl chloride and then chlorines can be substituted with azides of sodium azide to achieve azide-terminated (Si-g-P(PEGMA-N(3))) brushes. On the other hand, the terminal acetylene (Si-g-P(PEGMA-CH(2)C[triple bond]CH)) brushes can be prepared easily by reaction between Si-g-P(PEGMA-OH) and propargyl bromide. Model compounds of acetylene-terminated propargylamine, propiolic acid, and 10-undecynoic acid as well as azide-terminal benzyl azide were chosen to investigate the surface click reactions catalyzed with Cu(II)/sodium L-ascorbate by microwave irradiation under very mild conditions at 30°C for 1h. The stepwise modifications were characterized by two surface-sensitive techniques, Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) and X-ray Photoelectron Spectroscopy (XPS), and their spectra were analyzed in detail. The triazole ring v(H-C=) stretching at 3139 cm(-1) and the XPS high-resolution scan of N 1s directly confirm the click reactions. By quantifying their infrared spectra before and after click reactions, we conclude that the click reactions on silicon surfaces by microwave irradiation possess high yield and efficiency. Hence, the microwave irradiated click reaction approaches might open convenient avenues to fabricate functional and hybrid organic/silicon devices., (Copyright © 2011 Elsevier Inc. All rights reserved.)