DDB2 and MDM2 genes are promising markers for radiation diagnosis and estimation of radiation dose independent of trauma and burns.

In the field of biodosimetry, the current accepted method for evaluating radiation dose fails to meet the need of rapid, large-scale screening, and most RNA marker-related studies of biodosimetry are concentrating on a single type of ray, while some other potential factors, such as trauma and burns, have not been covered. Microarray datasets that contain the data of human peripheral blood samples exposed to X-ray, neutron, and γ-ray radiation were obtained from the GEO database. Totally, 33 multi-type ray co-induced genes were obtained at first from the differentially expressed genes (DEGs) and key genes identified by weighted gene co-expression network analysis (WGCNA), and these genes were mainly enriched in DNA damage, cellular apoptosis, and p53 signaling pathway. Following transcriptome sequencing of blood samples from 11 healthy volunteers, 13 patients with severe burns, and 37 patients with severe trauma, 6635 trauma-related DEGs and 7703 burn-related DEGs were obtained. Through the exclusion method, a total of 12 radiation-specific genes independent of trauma and burns were identified. ROC curve analysis revealed that the DDB2 gene performed the best in diagnosis of all three types of ray radiation, while correlation analysis showed that the MDM2 gene was the best in assessment of radiation dose. The results of multiple-linear regression analysis indicated that such analysis could improve the accuracy in assessment of radiation dose. Moreover, the DDB2 and MDM2 genes remained effective in radiation diagnosis and assessment of radiation dose in an external dataset. In general, the study brings new insights into radiation biodosimetry.

[Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice].

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.

[Inhibition effect of active fraction from clove on PI3K/Akt/mTOR signaling pathway to induce apoptosis of human colon cancer HCT116 cells].

To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-Ⅰ(IGF-Ⅰ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 µg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/ß-actin after treatment of AFC(100 µg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 µg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-Ⅰ weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-Ⅰ group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-Ⅰ were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-Ⅰ group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.

Effect of Ca2+ to Sphingomyelin Investigated by Sum Frequency Generation Vibrational Spectroscopy.

The interactions between Ca2+ ions and sphingomyelin play crucial roles in a wide range of cellular activities. However, little is known about the molecular details of the interactions at interfaces. In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS). We show that Ca2+ ions can induce ordering of the acyl chains in the ESM monolayer. An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered. Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward. Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes. Such binding causes the phosphate moiety to dehydrate, resulting in the conformation change of the phosphate moiety. Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone. These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid. It will also shed light on the interactions of complex molecules at surfaces and interfaces.

Evolution of Nanoflowers and Nanospheres of Zinc Bisporphyrinate Tweezers at the Air/Water Interface.

Although the sophisticated Langmuir and Langmuir-Blodgett (LB) techniques facilitate the fabrication of uniform ultrathin monolayer and films, they are also revealed as powerful tools for the bottom-up construction of the nanostructures through the air/water interface. In this paper, unique nanoflowers or nanospheres were constructed based on the synthesized m-phthalic diamide-linked zinc bisporphyrinate tweezers using the Langmuir and LB techniques. It was found that the two tweezer-type zinc bisporphyrinates could form stable two-dimensional spreading films at the air/water interface, which could be subsequently transferred onto solid substrates using the vertical lifting method. Atomic force microscopy (AFM) revealed that at the initial spreading stage, the compound formed flat disklike domains and then hierarchically evolved into nanoflowers or nanospheres upon compressing the floating film. Such nanostructures have not been reported before and cannot be fabricated using the other self-assembly methods.

Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins.

BACKGROUND: Previous studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). METHODS: One hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot. RESULTS: Our data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment. CONCLUSIONS: These findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.

Allergic reactions to antivenom in a patient bitten twice by the same snake within a month: A rare case report and literature review.

Antivenom is the most effective method currently available for the treatment of poisonous snake bite. Allergic reactions to antivenom have been reported in the past. Here we shared a case of allergic reactions to antivenom in an old male patient who was bitten twice by the same snake (probably same one) at the same biting site within a month whereas the patient did not show any allergic disorder in the first bitten. Envenomations twice in a short period time by the same kind of snake are very rare. Physician should be alert to the occurrence of allergic reactions in treating this type of patients with antivenom. The skin allergy test has a certain value in predicting the allergic response before the second use of antivenom. Desensitization may reduce the incidence of allergic reactions, but this is insufficient. Rather than non-IgE-mediated immediate hypersensitivity, patients receiving the second treatment of antivenom may develop IgE-mediated immediate hypersensitivity. Once happened, the antivenom treatment should be stopped promptly and anti-allergy treatment should be given immediately.

p-type Li, Cu-codoped NiOx hole-transporting layer for efficient planar perovskite solar cells.

p-type inorganic hole transport materials of Li, Cu-codoped NiOx films were deposited using a simple solution-based process. The as-prepared films were used as hole selective contacts for lead halide perovskite solar cell. An enhanced power conversion efficiency of 14.53% has been achieved due to the improved electrical conductivity and optical transmittance of the Li, Cu-codoped NiOx electrode interlayer.

[Chiral Transformation of PARC18 Assemblies on NaOH Solution Subphase].

Achiral molecules with conjugated structures can form chiral supramolecules through interfacial self-assembly. These spontaneous symmetry breaking processes may help elucidate the origin of life and are thus of great importance. So far, the mechanism of interfaciam self-assembly has been discussed in detail. However, dynamics of the chiral assemblies was rarely investigated. In order to clarify whether the chiral structures are stable or dynamic, we employed second harmonic generation linear dichroism (SHG-LD) to investigate the supramolecular chirality of PARC18 at air/aqueous interface. It was shown that PARC18 formed chiral structures with stable chiral state at air/water interface. While at air/NaOH solution interface, the chiral state changed with time. In addition, on NaOH solution subphase, contributions of magnetic dipole to second harmonic signals were dominant. We suggest that this is due to isomerization of PARC18 molecules on NaOH solution subphase. As a result, the two chromophores coupled with each other and the magnetic dipole contribution was enhanced.

[Study of the Detecting System of CH4 and SO2 Based on Spectral Absorption Method and UV Fluorescence Method].

According to the spectral absorption characteristics of polluting gases and fluorescence characteristics, a time-division multiplexing detection system is designed. Through this system we can detect Methane (CH4) and sulfur dioxide (SO2) by using spectral absorption method and the SO2 can be detected by using UV fluorescence method. The system consists of four parts: a combination of a light source which could be switched, the common optical path, the air chamber and the signal processing section. The spectral absorption characteristics and fluorescence characteristics are measured first. Then the experiment of detecting CH4 and SO2 through spectral absorption method and the experiment of detecting SO2 through UV fluorescence method are conducted, respectively. Through measuring characteristics of spectral absorption and fluorescence, we get excitation wavelengths of SO2 and CH4 measured by spectral absorption method at the absorption peak are 280 nm and 1.64 µm, respectively, and the optimal excitation wavelength of SO2 measured by UV fluorescence method is 220 nm. we acquire the linear relation between the concentration of CH4 and relative intensity and the linear relation between the concentration of SO2 and output voltage after conducting the experiment of spectral absorption method, and the linearity are 98.7%, 99.2% respectively. Through the experiment of UV fluorescence method we acquire that the relation between the concentration of SO2 and the voltage is linear, and the linearity is 99.5%. Research shows that the system is able to be applied to detect the polluted gas by absorption spectrum method and UV fluorescence method. Combing these two measurement methods decreases the costing and the volume, and this system can also be used to measure the other gases. Such system has a certain value of application.

[Expression profiles of miRNA-182 and Clock mRNA in the pineal gland of neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the changes of miRNA expression in the pineal gland of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible roles of miRNA in the pathogenesis of circadian rhythm disturbance after HIBD. METHODS: Seven-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups: HIBD and sham-operated. HIBD was induced according to the Rice-Vannucci method. The pineal glands were obtained 24 hours after the HIBD event. The expression profiles of miRNAs were determined using GeneChip technigue and quantitative real-time PCR (RT-PCR). Then the miRNA which was highly expressed was selected. The expression levels of the chosen miRNA were detected in different tissues (lungs, intestines, stomach, kidneys, cerebral cortex, pineal gland). RT-PCR analysis was performed to measure the expression profiles of the chosen miRNA and the targeted gene Clock mRNA in the pineal gland at 0, 24, 48 and 72 hours after HIBD. RESULTS: miRNA-182 that met the criteria was selected by GeneChip and RT-PCR. miRNA-182 was highly expressed in the pineal gland. Compared with the sham-operated group, the expression of miRNA-182 was significantly up-regulated in the pineal gland at 24 and 48 hours after HIBD (P<0.05). Compared with the sham-operated group, Clock mRNA expression in the HIBD group increased at 0 hour after HIBD, decreased at 48 hours after HIBD and increased at 72 hours after HIBD (P<0.05). CONCLUSIONS: miRNA-182 may be involved in the pathogenesis of circadian rhythm disturbance after HIBD.

Transcriptome analysis of leaves, roots and flowers of Panax notoginseng identifies genes involved in ginsenoside and alkaloid biosynthesis.

BACKGROUND: Panax notoginseng (Burk.) F.H. Chen is one of the most highly valued medicinal plants in the world. The major bioactive molecules are triterpene saponins, which are also known as ginsenosides. However, its large genome size has hindered the assembly of a draft genome by whole genome sequencing. Hence, genomic and transcriptomic details about P. notoginseng, especially its biosynthetic pathways and gene expression in different parts of the plant, have remained largely unknown until now. RESULTS: In this study, RNA sequencing of three different P. notoginseng tissues was performed using next generation DNA sequencing. After assembling the high quality sequencing reads into 107,340 unigenes, biochemical pathways were predicted and 9,908 unigenes were assigned to 135 KEGG pathways. Among them, 270 unigenes were identified to be involved in triterpene saponin biosynthesis. In addition, 350 and 342 unigenes were predicted to encode cytochrome P450s and glycosyltransferases, respectively, based on the annotation results, some of which encode enzymes responsible for the conversion of the triterpene saponin backbone into different ginsenosides. In particular, one unigene predominantly expressed in the root was annotated as CYP716A53v2, which probably participates in the formation of protopanaxatriol from protopanaxadiol in P. notoginseng. The differential expression of this gene was further confirmed by real-time PCR. CONCLUSIONS: We have established a global transcriptome dataset for P. notoginseng and provided additional genetic information for further genome-wide research and analyses. Candidate genes involved in ginsenoside biosynthesis, including putative cytochrome P450s and glycosyltransferases were obtained. The transcriptomes in different plant tissues also provide invaluable resources for future study of the differences in physiological processes and secondary metabolites in different parts of P. notoginseng.

The development of adultoid reproductives and brachypterous neotenic reproductives from the last instar nymphs in Reticulitermes labralis (Isoptera: Rhinotermitidae): a comparative study.

Secondary reproductives develop primarily from nymphs. However, they have been rarely studied; in particular, the development of adultoid reproductives (AR) with floppy wings is still unclear. In this study, the change in juvenile hormone (JH) levels, vitellogenin gene expression, and oogenesis during the development of AR and brachypterous neotenic reproductives (BN) from the last instar nymphs of Reticulitermes labralis are investigated and compared. The results showed that the AR derived from the last instar nymphs by molting, and they were more similar to neotenic reproductives in morphology. In addition, the paired AR were not able to survive in the absence of workers. In R. labralis, the process of the last instar nymphs developing into AR and BN took an increase in JH level as a starting point. The JH level of the last instar nymphs molting into BN was approximately 1.5-fold higher than that of the AR. Additionally, The JHIII level of BN peaked on day 5, and that of AR peaked on day 10, which induced the onset of vitellogenesis in BN and AR, respectively. After molting, the vitellogenin gene expression levels of both BN and AR initially increased and then declined, and the expression levels in the BN were significantly higher than those in the AR. In addition, the oocytes of BN matured earlier than those of the AR, and the number of eggs laid by the BN was higher than the number laid by the AR. Our results demonstrate that, in R. labralis, the last instar nymphs can develop into AR, which are significantly different from BN in their development.

Cervical sympathetic block regulates early systemic inflammatory response in severe trauma patients.

BACKGROUND: This aim of this study was to investigate the effects of one-side cervical sympathetic block on early inflammatory response in severe trauma patients. MATERIAL AND METHODS: Thirty severe trauma patients with injury severity score (ISS) of 16 to 25 were randomly divided into treatment and control groups (n=15 each). Patients in the treatment group underwent a right-side stellate ganglion block (SGB) using 8 mL 0.75% ropivacaine for 4 times, with the first injection within 12 hr of admission and the other 3 injections were 12 hr, 24 hr and 48 hr later. The same procedures were performed for the control group except that normal saline was injected instead of ropivacaine. Blood was collected before injection and at 6 hr, 24 hr, and 72 hr after the first SGB for serum interleukin (IL)-1beta, IL-4, IL-6, IL-10 and TNF-alpha measurement. RESULTS: The concentrations of IL-1beta, IL-6, and TNF-alpha between 24 hr to 72 hr after SGB were all significantly lower than those in the control group (all P values <0.01). However, there was no significant difference in the concentrations of anti-inflammatory IL-4 and IL-10 between treatment and control groups. There was no obvious impact of SGB on breathing and circulation except for a slower heart rate 10 to 50 min after injection (P<0.01). CONCLUSIONS: SGB regulates early inflammatory response through inhibition of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha during severe trauma. SGB has no impact on the levels of anti-inflammatory cytokines IL-4 and IL-10.

Association Between Cholecystectomy and Gastric Cancer Risk: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although several epidemiological studies have attempted to evaluate the relationship between cholecystectomy and gastric cancer risk, the findings have been controversial. This study aimed to carry out a systematic review and meta-analysis following the reporting guidelines to comprehensively analyze and quantify the evidence of the aforementioned association. METHODS: Studies were identified by searching the Medline (PubMed), Embase, and Web of Science from inception to November 30, 2020, with only studies published in English being considered. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. RESULTS: Eight studies (five cohort studies and three case-control studies) with a total of 26,063 gastric cancer patients and 848,081 participants were included. The summarized RR of the relationship between cholecystectomy and gastric cancer risk was 1.11 (95%CI: 1.03-1.20), with low heterogeneity (P = 0.117, I 2 = 37.8%). These positive findings were consistent in most subgroup analyses like region in Asia, number of cases ≥200, cohort study design, sex in male, low risk of bias, exposure collection by database, and adjustments made for age, gender, calendar year. Of note, we also observed positive association between cholecystectomy and non-cardia of gastric cancer risk (RR = 1.17, 95%CI: 1.04-1.33). No publication bias was present. CONCLUSIONS: The aforementioned evidence suggested that a history of cholecystectomy was associated with a slightly elevated risk of gastric cancer. Results of most subgroup analyses also supported the main findings. More prospective studies are warranted to further validate these findings.

Effects of different concentrations of intraluminal sodium chloride solution on intracavitary ECG used for arm infusion port implantation.

At present, there are few clinical studies on the application of high-concentration sodium chloride solutions in intracavitary ECG-guided catheter tip localization during the arm infusion port implantation. This study observed the effects of sodium chloride solutions with different concentrations on intracavitary ECG-guided arm infusion port implantation in the patients with cancer. The 657 patients receiving arm infusion port implantation in our hospital between January 2020 and August 2021 were randomly divided into 0.9% sodium chloride solution conduction group (group A), 5.45% sodium chloride solution conduction group (group B) and 10% sodium chloride solution conduction group (group C). The derived rate of stable intracavitary ECG, the occurrence rate of characteristic P wave, the time used for catheter tip localization and the optimal position rate of catheter tip were compared between the three groups. The derived rate of stable intracavitary ECG was significantly higher in the group B (97.78%) and group C (98.63%) than in the group A (93.90%) (all P < 0.05). The occurrence rate of characteristic P wave was also significantly higher in the group B (96.89%) and group C (97.72%) than in the group A (88.73%) (all P < 0.001). The time used for catheter tip localization was significantly shorter in the group B [(49.73 ± 8.15) s] and group C [(48.27 ± 8.61) s] than in the group A [(69.37 ± 19.99) s] (all P < 0.001). There was no significant difference in the optimal position rate of catheter tip among the three groups (P > 0.05). The 5.45% and 10% sodium chloride solutions are significantly superior comparing with 0.9% sodium chloride solution in the derived rate of stable intracavitary ECG, occurrence rate of characteristic P wave and time used for catheter tip localization, but there were no significant differences between 5.45 and 10% sodium chloride solutions. Moreover, the 5.45% sodium chloride solution is closer to physiological state comparing with 10% sodium chloride solution, so the 5.45% sodium chloride solution may be recommended for the intracavitary ECG-guided arm infusion port implantation.

First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate.

BACKGROUND: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. CASE PRESENTATION: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. CONCLUSIONS: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Molecular Hydrogen Reduces Electromagnetic Pulse-Induced Male Rat Reproductive System Damage in a Rodent Model.

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP.

Procyanidin B2 inhibits lipopolysaccharide­induced apoptosis by suppressing the Bcl­2/Bax and NF­κB signalling pathways in human umbilical vein endothelial cells.

Human umbilical vein endothelial cells (HUVECs) serve a critical role in maintaining normal vascular function. Lipopolysaccharide (LPS), which is released from pathogenic bacteria in the blood, induces HUVEC apoptosis and injury to cause vascular dysfunction and infectious vascular diseases. Procyanidin B2 (PB2) possesses numerous functions, including antioxidant, antitumor, anti­inflammatory and antiapoptosis effects, but the molecular mechanism is not completely understood. The present study investigated the effects of PB2 on LPS­induced cytotoxicity and apoptosis in HUVECs, as well as the underlying mechanisms. The effects of PB2 on LPS­mediated alterations to cytotoxicity, mitochondrial membrane potential, apoptosis were assessed by performing Cell Counting Kit­8, JC­1 fluorescence, Hoechst 33258 staining assays, respectively. IL­1ß, IL­6 and TNF­α mRNA expression and protein levels were measured by performing reverse transcription­quantitative PCR and ELISAs, respectively. Bcl­2, Bax, cleaved caspase­3, cleaved caspase­7, cleaved caspase­9, phosphorylated (p)­IκB­α, p­IκB­ß, p­NF­κB­p65 and total NF­κB p65 protein expression levels were determined via western blotting. NF­κB p65 nuclear translocation was assessed via immunofluorescence. PB2 pretreatment markedly attenuated LPS­induced cytotoxicity and apoptosis in HUVECs. PB2 also significantly downregulated the expression levels of IL­1ß, IL­6, TNF­α, Bax, cleaved caspase­3, cleaved caspase­7, cleaved caspase­9 and p­NF­κB­p65, but upregulated the expression levels of Bcl­2, p­IκB­α and p­IκB­ß in LPS­induced HUVECs. Moreover, PB2 markedly inhibited LPS­induced NF­κB p65 nuclear translocation in HUVECs. The results suggested that the potential molecular mechanism underlying PB2 was associated with the Bax/Bcl­2 and NF­κB signalling pathways. Therefore, PB2 may serve as a useful therapeutic for infectious vascular diseases.