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In the past decades, messenger RNA (mRNA) biomarkers have been employed to identify the origin of body fluids in forensic medicine. We hypothesized that the polymorphism of mRNA could be applied to identify individuals in mixture samples composed of two body fluids. In this study, we selected five blood-specific mRNA biomarkers of venous blood (SPTB, CD3G, AMICA1, ANK1, and GYPA) that encompass 16 SNPs to identify the mixture contributor(s). Five specific gene markers for menstrual blood, semen, skin, saliva, and vaginal secretions were amplified and typed as body-fluid positive controls. We established the system of multiplex PCR and single base extension (SBE) reaction followed by CE. The amplicon size was between 90bp and 294bp. The peripheral blood specificity was examined against other human body fluids, including saliva, semen, skin, menstrual blood, and vaginal secretion. The 16 SNPs were peripheral blood specific and could be successfully typed in homemade mixtures which are composed of different body fluids with 1 ng peripheral blood mRNA added. This system showed a supersensitivity (1:100) in detecting the trace amount of peripheral blood mixed in other body fluids and a combined discrimination power (CDP) of 0.99929 in Chinese population. It was the first time to establish a method for identifying the blood donors and deconvoluting mixtures through detecting mRNA polymorphism with SNaPshot assay. This peripheral blood specific SNP typing system showed high sensitivity to the typing of blood source specific markers regardless of other body fluids in the mixture.

Background: Primary pulmonary hypertension (PPH) is a life-threatening disease associated with increased mortality. The urea cycle pathway plays a major role in PPH severity and treatment response. Little is known about the association of the blood urea nitrogen (BUN) and PPH prognosis.Methods: Clinical data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Adult patients (≥18 years) patients with primary pulmonary hypertension (PPH) in the database were enrolled. Spearman correlation was used to analyze the association of BUN with length of hospital and intensive care unit (ICU) stays. The chi-square test was used to analyze the association of BUN with mortality rate. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariable logistic regression was used to identify the BUN as an independent prognostic factor of mortality. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the sensitivity and specificity for mortality.Results: In total, 263 patients who met the selection criteria were enrolled. BUN was significantly positively associated with length of hospital stay and ICU stay (hospital stay: ρ = 0.282, ICU stay: ρ = 0.276; all P < 0.001). Higher hospital, 90-day and 4-year mortality rates were observed in the higher BUN quartile of PPH patients (hospital: P = 0.002; 90-day: P = 0.025; 4-year: P < 0.001). The Kaplan-Meier survival curves showed that patients in higher BUN quartile tended to have lower 4-year survival (Q1:7.65%, Q2: 10.71%; Q3: 14.80%, Q4: 16.84%; P < 0.0001). Logistic regression analyses found a significant association of BUN and mortality (hospital: OR = 1.05, 95% CI = 1.02–1.08, P = 0.001; 90-day: OR = 1.02, 95% CI = 1.00–1.05, P = 0.027; 4-year: OR = 1.05, 95% CI = 1.02–1.08, P = 0.001). Results of ROC and AUC showed that the diagnostic performance of BUN for mortality was moderately good.Conclusion: BUN was positively correlated with the length of hospital stay and ICU stay of PPH patients. Higher BUN was associated with higher hospital, 90-day and 4-year mortality and lower 4-year survival of PPH patients. These findings indicate that BUN can be a novel potential prognostic predictor for PPH.

Allicin has been reported to play a biological role in human pathophysiological processes via interaction with numerous signaling pathways and gene expression alteration. The purpose of the present study was to evaluate the protective effects of allicin against renal ischemia/reperfusion injury (RIRI) in rats. In the present study, the RIRI model with 45-min ischemia and 22-h reperfusion in rats was generated and allicin was used as the intervention. Changes in renal tissue pathomorphology, renal function, oxidative stress, inflammatory response and apoptosis were evaluated in the RIRI model in rats. Compared with those in the RIRI group, renal function, renal pathological injury, and anti-inflammatory and antioxidant properties were markedly improved in the RIRI+allicin group. Thus, our research suggested that allicin exerted its protective effect against ischemia/reperfusion-induced renal injury by regulating apoptosis, oxidative stress and inflammatory response in rats.

Associations between gene variations and sudden cardiac arrest or coronary artery disease have been reported by genome-wide association studies. However, the implication of the genetic status in cases of sudden coronary death (SCD) from the Chinese Han population has remained to be investigated. The present study established a mini-sequencing system to examine putative death-causing single nucleotide polymorphisms (SNPs) using multiplex PCR, single base extension reaction and capillary electrophoresis techniques. A total of 198 samples from the Chinese Han population (age range, 34-71 years; mean age, 53.86 years) were examined using this method. Samples were classified into three groups: Coronary heart disease (CHD, n=70), SCD (n=53) and control (n=75) group. Significant associations were identified for 10, 4 and 6 SNPs in CHD, SCD and sudden death from CHD, respectively, using the χ2 test. The SNPs obtained by binary logistic regression may be used to assess and predict the risk of disease. The predictive accuracy of the SNPs in each prediction model and their area under the receiver operating characteristic curve (AUC) values were determined. The AUC of the four SNPs (rs12429889, rs10829156, rs16942421 and rs12155623) to predict CHD was 0.928, the AUC of the six SNPs (rs2389202, rs2982694, rs10183640, rs597503, rs16942421 and rs12155623) to predict SCD was 0.922 and the AUC of the four SNPs (rs16866933, rs4621553, rs10829156 and rs12155623) to predict sudden death from CHD was 0.912. The multifactor dimensionality reduction values were as follows: 0.8690 (prediction model of CHD), 0.7601 (prediction model of SCD) and 0.7628 (prediction model of sudden death from CHD). Taken together, the results of the present study suggested that these SNPs have considerable potential for application in genetic tests to predict CHD or SCD. However, further studies are required to investigate the putative functions of these SNPs.

Objective: To investigate the prognostic significance of the platelet-to-lymphocyte ratio (PLR) for newborn patients in the neonatal intensive care unit (NICU).Design: A retrospective cohort study.Setting and participants: Data on 5240 newborn patients in the NICU extracted from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database.Methods: Spearman correlation was used to analyze the association of PLR with length of hospital and ICU stays. The chi-square test was used to analyze the association of PLR with mortality rate. Multivariable logistic regression was used to determine whether the PLR was an independent prognostic factor of mortality. The area under the receiver operating characteristic (ROC) curve was used to assess the predictive ability of models combining PLR with other variables.Results: PLR was negatively associated with length of hospital stay and ICU stay (hospital stay: Spearman’s rho=-0.416, PPPP=0.005) and 90-day mortality (OR=0.85, 95% CI=0.76-0.96, P=0.010). The prognostic predictive ability of models combining PLR with other variables for hospital mortality was moderately good (AUC for Model 1=0.804; AUC for Model 2=0.964).Conclusion: PLR is a novel independent risk factor for newborn patients in the NICU.

Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC.

Electrical injury is a relatively uncommon but potentially devastating form of multi-system injury with high morbidity and mortality. In common electric injury cases, it is usually difficult to find characteristic changes of electric injury in major organs by using routine histopathological test methods unless there are landmark traces of electric injury, known as electric marks. How to determine electric shock death, especially in the absence of typical electrical marks on the body surface in some cases (which account for about two-thirds of electric injury cases), remains a challenging problem in forensic practice. Our summary shows that many current related studies have focused their efforts to find characteristic histopathological changes in major organs of the body caused by electric injury. Based on the results obtained through comparison of the literature, we find that it may be more urgent and important to find the optimal autopsy or sampling sites in cases with no typical electric marks, knowing that these sites may often reflect the most significant histopathological changes of electric injury, for instance anatomy and sampling of the anterior wrist and the medial malleolus in cases involving the hand-to-foot electric circuit pathway. In this article, we make a summary of advances in identification methods of electric injury, hoping that it could provide some new insights for further research in this field.

Tetrabromodiphenyl ether (BDE-47) is widely used as commercial flame retardants that can be released into the environment and finally enter human body through the food chain. It has been identified to generate neurotoxicity, but little is known about auditory damage and the underlying mechanism following BDE-47 exposure. This study aimed to assess the cell viability with BDE-47 concentration ranging from 0 to 150 μM in mouse organ of Corti-derived cell lines (HEI-OC1). Aryl hydrocarbon receptor (AhR) as an environmental sensor, reactive oxygen species (ROS), NLRP3 inflammasome and p38 MAPK pathways were detected. Results: (1) BDE-47 inhibited the viability in a time- and dose-dependent way in HEI-OC1 cells. Cell cycle was arrested in G1 phase by BDE-47; (2) Elevated intracellular ROS, LDH levels and necrosis were found, which was alleviated by pretreatment with ROS scavenger N-acetylcysteine (NAC); (3) AhR plays an essential role in ligand-regulated transcription factor activation by exogenous environmental compounds. We found increased expression of AhR and decreased downstream targets of CYP 1A1 and CYP 1B1 in BDE-47-treated HEI-OC1 cells, which was reversed by the AhR antagonist CH-223191 for 2 h before BDE-47 exposure. No significant change was detected in CYP 2B; (4) Enhanced expressions of NLRP3 and caspase-1 were induced by BDE-47, with up-regulations of both pro-inflammatory factors for IL-1β, IL-6 and TNF-α, and anti-inflammatory factors for IL-4, IL-10 and IL-13, but down-regulation for IL-1α; (5) Additionally, the p38 MAPK signaling pathway was activated with increased phosphorylation levels of MKK/3/6, p38 MAPK and NF-kB. Overall, our findings illustrate a role of AhR in ROS-induced necrosis of cochlear hair cells by BDE-47 exposure, in which NLRP3 inflammasome and p38 MAPK signaling pathways are activated. The current study first elucidates the sense of hearing damage induced by BDE-47, and cell-specific or mixture exposures in vivo or human studies are needed to confirm this association.

Resveratrol (RES) is a natural non-flavonoid polyphenol with cardioprotective activities, antioxidant, antiplatelet, and antiinflammatory. However, its low aqueous solubility, chemical stability, and oral bioavailability, as well as a short circulation half-life greatly limit its clinical applications. To overcome these limitations of RES, we synthesized a methoxy poly(ethylene glycol)-b-oligomerization(D, L-Leucine) (mPEG-b-O(D, L-Leu)) nanoparticle (NP) as the carrier of RES and evaluated the myocardial-protective effectiveness of this RES/NP complex in rat myocardial ischemia-reperfusion injury models. We gauged the characterization of the NP through proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscope, and Fourier transform infrared spectroscopy and then loaded RES on the nanocarrier by hydrophobic interactions under physiological pH to extend the release time of RES and prolong its circulation half-life. Subsequently, we used rat cardiomyocytes (H9C2 cells) and rat MI/RI model to investigate the relationship between drug composition and myocardial preservation properties. It was found that RES was encapsulated quickly and efficiently, and displayed an effectual loading-capacity and in vitro sustained-release. Anti-MI/RI effect of the RES/NP complex was found satisfactory in rat models in vivo using free RES as the control. This study suggested that NP may prove to be a potent nanocarrier to augment the pharmacotherapy of RES against MI/RI.

It has been demonstrated that S1P receptors affect heart ischaemia-reperfusion (IR) induced injury. However, whether S1P receptors affect IR-induced cardiac death has not been investigated. The aim of this paper is to demonstrate the role of S1P receptors in IR-induced cardiac death. Healthy adult male Sprague-Dawley rats were assigned to the following groups: non-operation control group, sham operation group, IR group, IR group pretreated with DMSO, IR group pretreated with S1P3 agonist, IR group pretreated with an antagonist of S1P3, IR group pretreated with S1P2 and S1P3 antagonists, IR group pretreated with heptanol and antagonists of S1P2/3, and IR group pretreated with Gap26 and antagonists of S1P2/3 (heptanol acts as a Cx43 uncoupler and the mimic peptide Gap26 as Cx43 blocker). The groups with S1P2 or S1P3 agonist application before reperfusion were used to assess whether these can be used for therapy of IR. The haemodynamics, electrocardiograms (ECG), infarction area, and mortality rates were recorded. Immunohistological connexin 43 (Cx43) expression in the heart was detected in each group. Blocking S1P2/3 receptors with specific antagonists resulted in an increment of IR-induced mortality, increased infarction size, redistribution of Cx43 expression, as well as affecting the heart function. The infarction size, heart function, and mortality were totally or partially restored in the S1P2, S1P3 agonist-pretreated IR group, and the heptanol/Gap26-treated S1P2/3-blocked IR group. The S1P receptor S1P2/3 and Cx43 are involved in the IR-induced cardiac death.

Unbalanced DNA mixture is still a difficult problem for forensic practice. DIP-STRs are useful markers for detection of minor DNA but they are not widespread in the human genome and having long amplicons. In this study, we proposed a novel type of genetic marker, termed DIP-SNP. DIP-SNP refers to the combination of INDEL and SNP in less than 300bp length of human genome. The multiplex PCR and SNaPshot assay were established for 14 DIP-SNP markers in a Chinese Han population from Shanxi, China. This novel compound marker allows detection of the minor DNA contributor with sensitivity from 1:50 to 1:1000 in a DNA mixture of any gender with 1 ng–10 ng DNA template. Most of the DIP-SNP markers had a relatively high probability of informative alleles with an average I value of 0.33. In all, we proposed DIP-SNP as a novel kind of genetic marker for detection of minor contributor from unbalanced DNA mixture and established the detection method by associating the multiplex PCR and SNaPshot assay. DIP-SNP polymorphisms are promising markers for forensic or clinical mixture examination because they are shorter, widespread and higher sensitive.

Background The main cause of chronic renal allograft dysfunction (CRAD) still remains unclear. Insulin resistance (IR) may be a potential inducement, but there is insufficient evidence about this association. We aimed to establish a rat model of CRAD complicated with IR and to explore the function and pathologic changes of the renal allograft induced by IR. Methods F344-to-Lewis rats of CRAD were fed a high-fat diet to induce IR. They were divided into 3 groups: IR (CRAD+IR), CRAD, and control (CTL). Serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were measured to evaluate the renal function. The Homeostasis Model Assessment (HOMA)-IR index was detected by comparing the values of fasting serum insulin levels (FINS) with fasting blood glucose levels (FBG). The pathologic analysis was conducted by the degree of renal lesions including glomerular lesions, renal tubular lesions, hemorrhage, inflammatory cell infiltration, fibrillation, and hyperplasia of the renal interstitium. Results In the second, third, and fourth month after surgery, serum levels of Scr and BUN in the IR group were reduced more than those in the CRAD group, while they were both higher compared to the CTL group, suggesting that renal function in the CRAD group was declined. The HOMA-IR in the IR group was greater than that in the CRAD and CTL groups, showing that simple high-fat diet feeding significantly and steadily increased FINS and FBG in CRAD complicated with IR rats. Pathologic changes indicated that the CRAD rat model was successfully constructed and was still in the early-middle stages of renal lesions 4 months after surgery, yet IR presented a significant effect on CRAD. Conclusion These results indicate that the stable CRAD complicated with IR rat model can be established through a high-fat diet in CRAD rats in 4 months, and IR could be an influencing factor.

Rationale: Dysgerminoma is a rare malignant tumor of the ovary, more frequently occurring in young women. The main signs of pseudo-Meigs syndrome (PMS) are ascites and hydrothorax accompanying benign or malignant ovarian tumors (no fibroma or fibroma-like tumor). Patient concerns: A 19-year-old woman with fever and chest tightness for 2 days. Diagnoses: Pectoral-abdominal computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging revealed a large amount of right pleural effusion, a small amount of ascites, and a huge abdominopelvic mass measuring about 29.2cm × 11.8cm × 8.4 cm in the left ovary. The result of hydrothorax examination was consistent with the diagnosis of exudative pleural effusion. In addition, Rivalta-test showed a positive result and lactate dehydrogenase was elevated. The histopathological diagnosis was a giant germ cell tumor, which was consistent with dysgerminoma in terms of both morphology and immunophenotype. Based on these findings, a diagnosis of malignant ovarian neoplasm with PMS was made. Interventions: Surgical resection of the tumor was performed. Outcomes: The patient recovered well after operation, and the pleural effusion and abdominal ascites vanished. No recurrence was observed during the 1-year follow-up period. Lessons: Ovarian dysgerminoma with PMS is a rare malignant tumor of the ovary, which often occurs in young women. It should be considered in differential diagnosis of patients with a pelvic mass, ascites and pleural effusion. Early diagnosis and surgical treatment are beneficial to prolonged survival.

The Identity By Descent (IBD) method and Identity By Sharing (IBS) scoring methods implement individual-to-individual comparison based on statistical data. Here, the researchers used the integrativ...

Unbalanced and degraded mixtures (UDM) are frequently encountered during forensic DNA analysis. For example, forensic DNA units regularly encounter DNA mixture signal where the DNA signal from the alleged offender is masked or swamped by high quantities of DNA from the victim. Our previous data presented a new kind of DNA markers that composed of a deletion/insertion polymorphism (DIP) and a SNP and we termed this new kind of microhaplotypes DIP-SNP (combination of DIP and SNP). Since such markers could be designed short enough for degraded DNA amplification, we hypothesized that DIP-SNP markers are applicable for typing of UDM. In this study, we developed a new set of DIP-SNPs with short amplicons which were complement to our prior developed system. The multiplex PCR and SNaPshot assay were established for 20 DIP-SNPs in a Chinese Han population. The DIP-SNPs were capable of detecting the minor contributor's allele in home-made DNA mixture with sensitivities from 1:100 to 1:1000 with a total of 1 -10 ng input DNA. Moreover, this system successfully typed the degraded DNA whether it came from the single source or mixture samples. In Chinese population, the system showed an average informative value of 0.293 and combined informative value of 0.998363862. Our results demonstrated that DIP-SNPs may serve as a valuable tool in detection of UDM in forensic medicine.

The Soil Moisture Experiment in the Luan River (SMELR) was conducted from 2017 to 2018 in the semi-arid Luan River watershed located in the North of China. One of the objectives of SMELR is to serve as an assessment tool and demonstration for a new Terrestrial Water Resources Satellite (TWRS) concept with one-dimensional synthetic aperture microwave techniques, for which soil moisture retrieval under variable satellite observing configurations (mainly in terms of incidence angels) is the greatest challenge. This proposed mission is targeted to provide continuity for the current satellite L-band microwave observations, and further improve the accuracy and spatial resolution of soil moisture mapping through the synergistic use of active, passive and optical remote sensing data. Multi-resolution, multi-angle and multi-spectral airborne data were obtained four times over a 70 km by 12 km area in the Shandian River basin, and one time over a 165 km by 5 km area that includes the Xiaoluan River basin. The near surface soil moisture (0 cm–5 cm) was measured extensively on the ground in fifty 1 km by 2 km quadrats (targeted to compare with the airborne radiometer), and two hundred and fifty 200 m by 200 m quadrats corresponding to radar observations. Two networks were established for continuous measurement of the soil moisture and temperature profile (3 cm, 5 cm, 10 cm, 20 cm, 50 cm) and precipitation in the Shandian and Xiaoluan River basin, respectively. Supporting ground measurements also included ground temperature, vegetation water content, surface roughness, continuous measurement of microwave emission and backscatter at a pasture site, reflectance of various land cover types, evapotranspiration and aerosol observations. Preliminary results within the experimental area indicate that (1) the near surface soil moisture spatial variability at a 200 m scale was up to ~0.1 cm3/cm3 at an intermediate value of ~0.35 cm3/cm3. (2) The difference of soil and vegetation temperature in grass and croplands reach its maximum of 11 K around solar noon time, and the soil temperature gradient is largest at around 15 P.M. (3) Both the airborne and ground measurements cover a wide range of conditions. The L-band active and passive observations exhibit a large variation of ~30 dB and ~80 K, respectively, corresponding to soil moisture range from 0.1 cm3/cm3 to 0.5 cm3/cm3. The sensitivity of both active and passive data to soil moisture is compared at corresponding spatial resolutions and show high information complementarity for better accuracy and resolution soil moisture retrieval.

Background: SCD (Sudden Cardiac Death) occurs commonly in forensic practice and often shows negative anatomy results after a systemic autopsy. In recent years, the importance of genetic background has been emphasized in the examination of SCD. The aim of this study is to establish a feasible method to detect SCD-related mutations located in a SCD-causing gene, potassium voltage-gated channel gene (KCNQ1). This method will meet the requirement of mutation screening for SCD in regular forensic DNA laboratories. Methods: 51 reported single nucleotide polymorphisms (SNPs) from KCNQ1 gene were selected in our study. We examined 60 SCD victims and 60 healthy individuals from the Chinese population residing in Shanxi and Chongqing, China. We performed multiplex PCR for 16 DNA fragments, then using SNaPshot reaction and capillary electrophoresis to obtain the typing results of 51 SNPs. Finding: Four previously reported coding variants were identified in our study: S546S, I145I, P448R and G643S. The allele frequencies of I145I did not differ significantly in the SCD cases compared with Chinese controls (I145I: 10% in SCD cases vs 6% in controls, p=0*301, OR=0*965). The heterozygous mutation of G643S and P448R probably were putative causative mutation for SCD in Chinese population (G643S: 40% in SCD cases vs 10% in controls, p

To occupy the domestic and international Point-of-purchase (POP) displays market, comparative research method has been used to analyze differences of between POP and traditional displays, and even the difference of POP displays at home and abroad. Market demands, design and material selection of POP displays were analyzed. Some enlightenment have been achieved for Chinese packaging enterprises. Results show that market demands of POP displays is huge and they are gradually replacing traditional displays. POP displays with easy assembling, technicolor and multiple-shapes have made them easily recognized and have attracted consumer’s more attention, indicating that they are more suitable for shopping malls by being compared with traditional displays. Ecological-friendly and low-cost corrugated cardboard as substitute of metal, plastic and wood has been applied into POP displays. POP displays will be widely used in major shopping malls and will cover most of the cities in China. Packaging enterprises should pay attention to research and develop POP displays.

In our previous paper [1], we proposed an efficient automatic test generating technique (BBATG) that leverages device behavior descriptions that are widely available for various IC devices (included VLSI). In this paper, we report further improvement on BBATG by leveraging techniques from JTAG (Joint Test Action Group) [2], we call this new technique BJATG. For a device equipped with JTAG, BJATG uses its own BSDL (Boundary Scan Description Language) file to create the device test library automatically. This greatly reduces the overhead to develop device behavior test libraries. Additionally, since JTAG is now available for most of VLSI devices, our technology has a better scalability. Traditional ATE (Automatic Test Equipment) use some type of test instrument bus, such as VXI or PXI Bus to connect to computer. It is usually bulky and requires special handlings. Our ATE leverages standard USB interface to communicate with the host computer, and we call it UATE. In addition to UUT (Unit Under Test) JTAG test interface, UATE has its own built-in JTAG BSC (Bound Scan Cell) chain circuit for UUT's other connector interfaces. With a simple USB structure and optimized interface design, the size of a UATE (not including main computer) is reduced to the size of an iPhone.