Ferroptosis and mitochondrial dysfunction in acute central nervous system injury.

Acute central nervous system injuries (ACNSI), encompassing traumatic brain injury (TBI), non-traumatic brain injury like stroke and encephalomeningitis, as well as spinal cord injuries, are linked to significant rates of disability and mortality globally. Nevertheless, effective and feasible treatment plans are still to be formulated. There are primary and secondary injuries occurred after ACNSI. Most ACNSIs exhibit comparable secondary injuries, which offer numerous potential therapeutic targets for enhancing clinical outcomes. Ferroptosis, a newly discovered form of cell death, is characterized as a lipid peroxidation process that is dependent on iron and oxidative conditions, which is also indispensable to mitochondria. Ferroptosis play a vital role in many neuropathological pathways, and ACNSIs may induce mitochondrial dysfunction, thereby indicating the essentiality of the mitochondrial connection to ferroptosis in ACNSIs. Nevertheless, there remains a lack of clarity regarding the involvement of mitochondria in the occurrence of ferroptosis as a secondary injuries of ACNSIs. In recent studies, anti-ferroptosis agents such as the ferroptosis inhibitor Ferrostain-1 and iron chelation therapy have shown potential in ameliorating the deleterious effects of ferroptosis in cases of traumatic ACNSI. The importance of this evidence is extremely significant in relation to the research and control of ACNSIs. Therefore, our review aims to provide researchers focusing on enhancing the therapeutic outcomes of ACNSIs with valuable insights by summarizing the physiopathological mechanisms of ACNSIs and exploring the correlation between ferroptosis, mitochondrial dysfunction, and ACNSIs.

Gut microbiome alterations in pulmonary hypertension in highlanders and lowlanders.

Background: Alterations in the gut microbiota have been observed in patients with pulmonary hypertension (PH), though whether the roles of the gut microbiota in PH at different altitudes are the same is unknown. This study aims to evaluate the associations of the gut microbiome with PH in highlanders and lowlanders. Methods: PH patients and controls were recruited from those who permanently live on the Tibetan plateau (highlanders) or the plains (lowlanders), and underwent transthoracic echocardiography close to their altitude of residence (at 5070 m for highlanders versus6 m for lowlanders). The gut microbiome was profiled using metagenomic shotgun sequencing. Results: In total, 13 PH patients (46% highlanders) and 88 controls (70% highlanders) were included. The overall microbial composition was different in PH patients compared to controls (p=0.003). Notably, among lowlanders, a composite microbial score of pro-atherosclerotic trimethylamine-producing species was increased in PH patients compared with that in controls (p=0.028), while among highlanders no such difference was observed (p=0.087). Another composite gut microbial score including eight species of Lactobacillus, which has shown beneficial effects on cardiovascular functions, was higher in highlanders than lowlanders (p<0.01). Furthermore, this score tended to be lower in PH patients than controls among highlanders (p=0.056) but not among lowlanders (p=0.840). In addition, the gut microbiome showed a good performance in distinguishing PH patients from controls in both lowlanders and highlanders. Conclusions: Our study reported differently altered gut microbiome profiles between highland and lowland PH patients, highlighting the distinct microbial mechanism in PH in highlanders compared with lowlanders.

[Characteristics and Assembly Process of Reclaimed Soil Microbial Communities in Eastern Plain Mining Areas].

Understanding how soil microorganisms respond to land reclamation is essential to evaluating the success of ecological restoration actions in disturbed mine soil. However, the microbiological mechanism referred to as productivity reconstruction of the reclaimed soil is still unclear. To shed light on this mechanism, a total of 75 soil samples were collected for 16S rRNA amplicon high-throughput sequencing. The five sampling sites contained four reclamation plots (reclaimed 8 a, 11 a, 14 a, and 17 a) and 1 non-reclaimed plot, which served as the control sampling site. The microbial community composition, potential functions, and assembly mechanisms were also analyzed. The results showed that:①the richness of the microbial community increased with the reclamation time and was higher than that of the control site. However, the community diversity and evenness decreased with the increasing reclamation year (P<0.05). ②Acidobacteria, Chloroflexi, Proteobacteria, and Bacteroidetes dominated in the reclaimed soil, and the relative abundances of the first two phyla were significantly higher than that of the control (P<0.05), whereas the latter two presented the opposite trends (P<0.05). ③ Eight functions, including coenzyme transport and metabolism, translation, ribosomal structure, and biogenesis, showed a positive succession in the reclamation sites and enhanced with increasing reclamation years. ④ The molecular ecological networks of the microbial community in the plain mining area were well modular, whereas the key microbial groups belonged to the Acidobacteria and Bacteroidetes. The microbial communities were dominantly assembled with the deterministic process, and the homogeneous selection contributed the most, which might have been mainly controlled by the local special environment. The results presented herein will undoubtedly aid in the establishment of success indicators of ecological restoration activities in disturbed mining soil. These findings also provide the theoretical basis for improving the productivity and ecological services of reclaimed soil.

Spatially adaptive blind deconvolution methods for optical coherence tomography.

Optical coherence tomography (OCT) is a powerful noninvasive imaging technique for detecting microvascular abnormalities. Following optical imaging principles, an OCT image will be blurred in the out-of-focus domain. Digital deconvolution is a commonly used method for image deblurring. However, the accuracy of traditional digital deconvolution methods, e.g., the Richardson-Lucy method, depends on the prior knowledge of the point spread function (PSF), which varies with the imaging depth and is difficult to determine. In this paper, a spatially adaptive blind deconvolution framework is proposed for recovering clear OCT images from blurred images without a known PSF. First, a depth-dependent PSF is derived from the Gaussian beam model. Second, the blind deconvolution problem is formalized as a regularized energy minimization problem using the least squares method. Third, the clear image and imaging depth are simultaneously recovered from blurry images using an alternating optimization method. To improve the computational efficiency of the proposed method, an accelerated alternating optimization method is proposed based on the convolution theorem and Fourier transform. The proposed method is numerically implemented with various regularization terms, including total variation, Tikhonov, and l1 norm terms. The proposed method is used to deblur synthetic and experimental OCT images. The influence of the regularization term on the deblurring performance is discussed. The results show that the proposed method can accurately deblur OCT images. The proposed acceleration method can significantly improve the computational efficiency of blind demodulation methods.

Targeted Sequencing Identifies the Genetic Variants Associated with High-altitude Polycythemia in the Tibetan Population.

High-altitude polycythemia (HAPC) is characterized by excessive proliferation of erythrocytes, resulting from the hypobaric hypoxia condition in high altitude. The genetic variants and molecular mechanisms of HAPC remain unclear in highlanders. We recruited 141 Tibetan dwellers, including 70 HAPC patients and 71 healthy controls, to detect the possible genetic variants associated with the disease; and performed targeted sequencing on 529 genes associated with the oxygen metabolism and erythrocyte regulation, utilized unconditional logistic regression analysis and GO (gene ontology) analysis to investigate the genetic variations of HAPC. We identified 12 single nucleotide variants, harbored in 12 genes, associated with the risk of HAPC (4.7 ≤ odd ratios ≤ 13.6; 7.6E - 08 ≤ p-value ≤ 1E - 04). The pathway enrichment study of these genes indicated the three pathways, the PI3K-AKT pathway, JAK-STAT pathway, and HIF-1 pathway, are essential, which p-values as 3.70E - 08, 1.28 E - 07, and 3.98 E - 06, respectively. We are hopeful that our results will provide a reference for the etiology research of HAPC. However, additional genetic risk factors and functional investigations are necessary to confirm our results further. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01474-1.

Smaller reaction volume of triplex taqman real-time reverse transcription-PCR assays for diagnosing coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a devastating impact on public health services worldwide. Currently, there are no standard remedies or therapies for COVID-19. it is important to identify and diagnose COVID-19 to control the spread. But clinical symptoms of COVID-19 are very similar to those of other respiratory viruses. RESULTS: As a result, the diagnosis of COVID-19 relies heavily on detecting pathogens. We established a bunch of triplex new TaqMan real-time PCR assays. Three sets of primers and probes (targeting the ORF1ab, N, and E genes, respectively) are poorly consistent with other human coronaviruses and the human influenza virus. The sensitivity of established PCR assays notices as few as 100 copies per PCR of the ORF1ab, N, and E genes. Meanwhile, standard curves concluded from constant PCR reaction all showed glorious linear correlations between Ct values and the polymer loading copy variety (correlation coefficient (R2 ) of ORF1ab, N, and E genes is 0.996, 0.991, and 0.998, respectively). Surveillance of RNA-based pseudovirus demonstrated that they were identified to be positive with respect to SARS-CoV-2 and that established PCR assays are achievable. CONCLUSION: The assays established provide a smaller reaction volume for diagnosing COVID-19.

Migration effects on the intestinal microbiota of Tibetans.

BACKGROUND: Diet, environment, and genomic context have a significant impact on humans' intestinal microbiota. Moreover, migration may be accompanied by changes in human eating habits and living environment, which could, in turn, affect the intestinal microbiota. Located in southwestern China, Tibet has an average altitude of 4,000 meters and is known as the world's roof. Xianyang is situated in the plains of central China, with an average altitude of about 400 meters. METHODS: To understand the association between intestinal microbiota and population migration, we collected the fecal samples from 30 Tibetan women on the first day (as TI1st), six months (as TI2nd), and ten months (as TI3rd) following migration from Tibet to Xianyang. Fecal samples were collected from 29 individuals (belonging to the Han women) as a control. The dietary information of the Tibetan women and the Han women was gathered. We performed a 16S rRNA gene survey of the collected fecal samples using Illumina MiSeq sequencing. RESULTS: Following the migration, the alpha and beta diversity of Tibetan women's intestinal microbiota appeared unaffected. Linear discriminant analysis effect size (LEfSe) analysis showed that Klebsiella, Blautia, and Veillonella are potential biomarkers at TI1st, while Proteobacteria and Enterobacteriaceae were common in TI3rd. Finally, functional prediction by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) found no significant up-regulation or down-regulation gene pathway in the intestinal microbiota of Tibetan women after migration. The present study reveals that the higher stability in Tibetan women's intestinal microbiota was less affected by the environment and diet, indicating that Tibetan women's intestinal microbiota is relatively stable. The main limitations of the study were the small sample size and all volunteers were women.

Effects of Helicobacter pylori Infection on the Oral Microbiota of Reflux Esophagitis Patients.

The human oral microbiota plays a vital role in maintaining metabolic homeostasis. To explore the relationship between Helicobacter pylori (Hp) and reflux esophagitis, we collected 86 saliva samples from reflux esophagitis patients (RE group) and 106 saliva samples from healthy people (C group) for a high-throughput sequencing comparison. No difference in alpha diversity was detected between the RE and the C groups, but beta diversity of the RE group was higher than the C group. Bacteroidetes was more abundant in the RE group, whereas Firmicutes was more abundant in the C group. The linear discriminant analysis effect size analysis demonstrated that the biomarkers of the RE group were Prevotella, Veillonella, Leptotrichia, and Actinomyces, and the biomarkers of the C group were Lautropia, Gemella, Rothia, and Streptococcus. The oral microbial network structure of the C group was more complex than that of the RE group. Second, to explore the effect of Hp on the oral microbiota of RE patients, we performed the 14C-urea breath test on 45 of the 86 RE patients. We compared the oral microbiota of 33 Hp-infected reflux esophagitis patients (REHpp group) and 12 non-Hp-infected reflux esophagitis patients (REHpn group). No difference in alpha diversity was observed between the REHpn and REHpp groups, and beta diversity of the REHpp group was significantly lower than that of the REHpn group. The biomarkers in the REHpp group were Veillonella, Haemophilus, Selenomonas, Megasphaera, Oribacterium, Butyrivibrio, and Campylobacter; and the biomarker in the REHpn group was Stomatobaculum. Megasphaera was positively correlated with Veillonella in the microbial network of the REHpp group. The main finding of this study is that RE disturbs the human oral microbiota, such as increased beta diversity. Hp infection may inhibit this disorderly trend.

Effects of altitude on human oral microbes.

Human oral microbes play a vital role maintaining host metabolic homeostasis. The Qinghai-Tibet Plateau is mainly characterized by a high altitude, dry, cold, and hypoxic environment. The oral microbiota is subject to selective pressure from the plateau environment, which affects oral health. Only a few studies have focused on the characteristics of oral microbiota in high-altitude humans. We collected saliva samples from 167 Tibetans at four altitudes (2800 to 4500 m) in Tibet to explore the relationship between the high altitude environment and oral microbiota. We conducted a two (high- and ultra-high-altitude) group analysis based on altitude, and adopted the 16S rRNA strategy for high-throughput sequencing. The results show that the alpha diversity of the oral microbiota decreased with altitude, whereas beta diversity increased with altitude. A LEfSe analysis revealed that the oral microbial biomarker of the high-altitude group (< 3650 m) was Streptococcus, and the biomarker of the ultra-high-altitude group (> 4000 m) was Prevotella. The relative abundance of Prevotella increased with altitude, whereas the relative abundance of Streptococcus decreased with altitude. A network analysis showed that the microbial network structure was more compact and complex, and the interaction between the bacterial genera was more intense in the high altitude group. Gene function prediction results showed that the amino acid and vitamin metabolic pathways were upregulated in the ultra-high-altitude group. These result show that altitude is an important factor affecting the diversity and community structure of the human oral microbiota.