Dissecting the association between gut microbiota and hypertrophic scarring: a bidirectional Mendelian randomization study.

Hypertrophic scars affect a significant number of individuals annually, giving rise to both cosmetic concerns and functional impairments. Prior research has established that an imbalance in the composition of gut microbes, termed microbial dysbiosis, can initiate the progression of various diseases through the intricate interplay between gut microbiota and the host. However, the precise nature of the causal link between gut microbiota and hypertrophic scarring remains uncertain. In this study, after compiling summary data from genome-wide association studies (GWAS) involving 418 instances of gut microbiota and hypertrophic scarring, we conducted a bidirectional Mendelian randomization (MR) to investigate the potential existence of a causal relationship between gut microbiota and the development of hypertrophic scar and to discern the directionality of causation. By utilizing MR analysis, we identified seven causal associations between gut microbiome and hypertrophic scarring, involving one positive and six negative causal directions. Among them, Intestinimonas, Ruminococcus2, Barnesiella, Dorea, Desulfovibrio piger, and Ruminococcus torques act as protective factors against hypertrophic scarring, while Eubacterium rectale suggests a potential role as a risk factor for hypertrophic scars. Additionally, sensitivity analyses of these results revealed no indications of heterogeneity or pleiotropy. The findings of our MR study suggest a potential causative link between gut microbiota and hypertrophic scarring, opening up new ways for future mechanistic research and the exploration of nanobiotechnology therapies for skin disorders.

Evaluation of monolithic crystal detector with dual-ended readout utilizing multiplexing method.

Objective.Monolithic crystal detectors are increasingly being applied in positron emission tomography (PET) devices owing to their excellent depth-of-interaction (DOI) resolution capabilities and high detection efficiency. In this study, we constructed and evaluated a dual-ended readout monolithic crystal detector based on a multiplexing method.Approach.We employed two 12 × 12 silicon photomultiplier (SiPM) arrays for readout, and the signals from the 12 × 12 array were merged into 12 X and 12 Y channels using channel multiplexing. In 2D reconstruction, three methods based on the centre of gravity (COG) were compared, and the concept of thresholds was introduced. Furthermore, a light convolutional neural network (CNN) was employed for testing. To enhance depth localization resolution, we proposed a method by utilizing the mutual information from both ends of the SiPMs. The source width and collimation effect were simulated using GEANT4, and the intrinsic spatial resolution was separated from the measured values.Main results.At an operational voltage of 29 V for the SiPM, an energy resolution of approximately 12.5 % was achieved. By subtracting a 0.8 % threshold from the total energy in every channel, a 2D spatial resolution of approximately 0.90 mm full width at half maximum (FWHM) can be obtained. Furthermore, a higher level of resolution, approximately 0.80 mm FWHM, was achieved using a CNN, with some alleviation of edge effects. With the proposed DOI method, a significant 1.36 mm FWHM average DOI resolution can be achieved. Additionally, it was found that polishing and black coating on the crystal surface yielded smaller edge effects compared to a rough surface with a black coating.Significance.The introduction of a threshold in COG method and a dual-ended readout scheme can lead to excellent spatial resolution for monolithic crystal detectors, which can help to develop PET systems with both high sensitivity and high spatial resolution.

High-performance coded aperture gamma camera based on monolithic GAGG:Ce crystal.

A 50 × 50 × 10 mm3 monolithic gadolinium aluminum gallium garnet (Gd3Al2Ga3O12; GAGG):Ce crystal coupled to a 8 × 8 silicon photomultiplier (SiPM) array was developed; it showed very good system uniformity and a high energy resolution of 7.4% at 662 keV. By using a convolutional neural network-based positioning algorithm and a fan-beam calibration method, the detector achieved a position resolution of ∼1.4 mm and a depth of interaction resolution of ∼2 mm. Based on this high-performance monolithic detector, we developed a coded aperture gamma camera. A 1-mCi Cs-137 source centered at a 2-m distance from the mask could be reconstructed with a signal-to-noise ratio of 6.5 in 1 s. Furthermore, the imaging ability of a low-energy Am-241 source and a low-activity Cs-137 source when the background-to-signal ratio was approximately 1:1 and a double low-activity source (Cs-137 and Na-22) was demonstrated. It is shown that the monolithic-crystal-based coded aperture gamma camera can achieve high performance and has a large potential for further improvement.

Relationship between SNP rs1764391 and Susceptibility, Risk Factors, Gene-environment Interactions of Acute Myocardial Infarction in Guangxi Han Chinese Population.

BACKGROUND: Large-scale population studies showed that the SNP rs1764391 of Connexin37 gene also known as Cx37 gene may play a pivotal role in the occurrence and development of acute myocardial infarction (AMI). Published results, however, are highly controversial. OBJECTIVE: This study aimed to examine the association between SNP rs1764391 of Cx37 and diseasesusceptibility, several risk factors, and gene-environment interactions of AMI in Guangxi Han Chinese population. METHODS: In this study, 344 healthy controls and 344 AMI patients of Han Chinese population were enrolled. The TaqMan assay was implemented to identify genotypes of Cx37 and allele frequencies of SNP rs1764391 in both the AMI and control groups. RESULTS: Significant differences were detected in TT genotype frequencies of SNP rs1764391 between the AMI and control groups (P < 0.05). In the context of gender stratification, the result was also statistically different in women (P < 0.05). Each variable such as age, BMI, diabetes, high blood pressure, smoking and TC was a risk factor and correlated significantly (P < 0.05) with the development of AMI. HDL-C correlated negatively with the risk of AMI (P < 0.001). BMI, smoking or alcohol consumed interacts significantly (P < 0.017) with the presence of the SNP rs1764391 CC genotype. CONCLUSION: Evidences were presented that Cx37 rs1764391 variation may contribute to the risk for AMI, especially in women and this genetic variant may prove to be a potential biomarker for AMI risk stratification and may prove to be a useful target for therapeutic intervention to further improve prognosis in high-risk patients.

Influence of rs1746048 SNPs on clinical manifestations and incidence of acute myocardial infarction in Guangxi Han population.

A relationship of the CXCL12 gene rs1746048 SNPs with AMI has been reported in American, European, Caucasian, and Pakistani populations. However, little is known about this association in the Guangxi Han population. In this study, we detect associations between rs1746048 SNPs and susceptibility, risk factors, clinical characteristics, and gene-environment interactions for AMI. 300 AMI patients and 300 healthy controls of Chinese Han were enrolled. Genotyping of rs1746048 SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and then confirmed by direct sequencing. Significant differences in both genotypic and allelic frequencies of rs1746048 SNPs between AMI and the control group were not detected (P > 0.05 for each). The frequency of CC genotypes of rs1746048 SNPs was the highest in the 2 h < DT ≤ 6 h subgroup (P < 0.05). The frequencies of the CT genotype and the T allele were significantly higher in the severe complications subgroup of AMI (P < 0.05). There were interactions between the subjects with rs1746048 SNPs and smoking or alcohol consumption (P < 0.017 for each). Rs1746048 SNPs were not correlated with the risk of AMI in present study. For the first time, we discovered that the CC genotype of the rs1746048 SNPs was significantly correlated with DT of AMI; the frequencies of the CT genotype and the minor T allele were positively correlated with the severe complications of AMI. Also, the interaction between the rs1746048 SNPs and smoking or alcohol appears to increase the risk of AMI exposure.

Role of high-mobility group B1 in myocardial injury induced by coronary microembolization in rats.

OBJECTIVE: This study aimed to explore the effects of high-mobility group B1 (HMGB1) on coronary microembolization (CME)-induced myocardial inflammation, myocardial apoptosis, and cardiac function injury in rats. METHODS: Forty Sprague-Dawley rats were divided into sham operation group (sham group), microembolization group (CME group), CME + HMGB1 siRNA (HMGB1 siRNA) group, and CME + scrambled siRNA (control siRNA) group (10 rats in each group). The CME model group was constructed by injecting microembolism spheres into the apex of the left ventricle after clamping the ascending aorta. The sham group was constructed by injecting the same amount of saline. The HMGB1 siRNA group was injected with HMGB1 siRNA transfection complex via the tail vein 72 hours before CME modeling. The control siRNA group was injected with the same amount of scrambled siRNA mixture through the tail vein 72 hours before CME modeling. The cardiac function, serum cardiac troponin I level, and apoptotic index were examined 12 hours after the surgery. The levels of HMGB1, nuclear factor-κB (NF-κB) p65, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, cleaved caspase-3, tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) were detected. RESULTS: Myocardial dysfunction, enhanced serum cardiac troponin I level, and apoptotic index were induced following CME. Moreover, CME increased the expression of HMGB1, NF-κB p65, GRP78, CHOP, cleaved caspase-12, cleaved caspase-3, TNF-α, and IL-1ß. HMGB1 siRNA reversed these effects, whereas scrambled siRNA had no effect. CONCLUSIONS: Inhibition of HMGB1 expression reduced CME-induced myocardial injury and improved cardiac function. Hence, it may serve as a new target for preventing and treating the CME-induced myocardial injury.