Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors.

Zokors, an Asiatic group of subterranean rodents, originated in lowlands and colonized high-elevational zones following the uplift of the Qinghai-Tibet plateau about 3.6 million years ago. Zokors live at high elevation in subterranean burrows and experience hypobaric hypoxia, including both hypoxia (low oxygen concentration) and hypercapnia (elevated partial pressure of CO2). Here we report a genomic analysis of six zokor species (genus Eospalax) with different elevational ranges to identify structural variants (deletions and inversions) that may have contributed to high-elevation adaptation. Based on an assembly of a chromosome-level genome of the high-elevation species, Eospalax baileyi, we identified 18 large inversions that distinguished this species from congeners native to lower elevations. Small-scale structural variants in the introns of EGLN1, HIF1A, HSF1 and SFTPD of E. baileyi were associated with the upregulated expression of those genes. A rearrangement on chromosome 1 was associated with altered chromatin accessibility, leading to modified gene expression profiles of key genes involved in the physiological response to hypoxia. Multigene families that underwent copy-number expansions in E. baileyi were enriched for autophagy, HIF1 signalling and immune response. E. baileyi show a significantly larger lung mass than those of other Eospalax species. These findings highlight the key role of structural variants underlying hypoxia adaptation of high-elevation species in Eospalax.

Progress in the Clinical Assessment and Treatment of Myocardial Depression in Critically Ill Patient with Sepsis.

Myocardial inhibition is the main cause of death in patients with sepsis.In recent years, methodological differences in the diagnosis, assessment, and treatment of septic myocardial depression have been observed, and how to objectively and accurately evaluate the degree of myocardial depression and the timing of treatment strategies have generally been the focus of this area of research. Based on the relevant research at home and abroad, the current review summarizes the clinical characteristics, methodological diagnosis, and symptomatic treatment of septic myocardial depression. The aim of doing so is to provide a reference for the early identification and treatment of patients with sepsis and myocardial depression.

Genomic insights into zokors' phylogeny and speciation in China.

The phylogeny and speciation of subterranean zokors in China are unclear, as previous studies on morphology and limited molecular markers have generated conflicting results. This study unraveled the complex evolutionary history of eight zokor species in China based on de novo assembly at chromosome level and whole-genome sequencing of 23 populations. We found extensive phylogenetic discordances between nuclear and mitochondrial phylogenies, and different coalescent phylogenies, which could be explained by introgression and incomplete lineage sorting (ILS). The recent Qinghai-Tibet Plateau uplift (∼3.60 million y ago; Mya) drove Eospalax to speciate into clade A and clade B (∼3.22 Mya), and discordant phylogenies in this node were mainly attributed to introgression rather than ILS. Clade A rapidly diverged into three lineages due to geographical isolation and glaciation, while glaciation and C4 plant expansion contributed to the speciation of clade B. ILS contributed to the discordances of two rapidly radiated nodes rather than introgression. The effective population sizes (Ne's) of all the species of Eospalax were affected by three glaciations. Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of all the species pairs. Positively selected genes putatively related to specific inhabitation adaptations were identified, such as heart development, neurogenesis, DNA repair, and immune response. Climate, geological tectonism, and C4 vegetation shaped the adaptation and speciation of zokors in China.

Sympatric speciation of the spiny mouse from Evolution Canyon in Israel substantiated genomically and methylomically.

SignificanceWhether sympatric speciation (SS) is rare or common is still debated. Two populations of the spiny mouse, Acomys cahirinus, from Evolution Canyon I (EC I) in Israel have been depicted earlier as speciating sympatrically by molecular markers and transcriptome. Here, we investigated SS both genomically and methylomically, demonstrating that the opposite populations of spiny mice are sister taxa and split from the common ancestor around 20,000 years ago without an allopatric history. Mate choice, olfactory receptors, and speciation genes contributed to prezygotic/postzygotic reproductive isolation. The two populations showed different methylation patterns, facilitating adaptation to their local environment. They cope with abiotic and biotic stresses, due to high solar interslope radiation differences. We conclude that our new genomic and methylomic data substantiated SS.

Ulinastatin plus biapenem for severe pneumonia in the elderly and its influence on pulmonary function and inflammatory cytokines.

To estimate the efficacy of ulinastatin (UTI) plus biapenem (BIPM) in the treatment of severe pneumonia in the elderly and its influence on pulmonary function (PF) and inflammatory cytokines. METHODS: We included 97 elderly patients with severe pneumonia in the present study. Patients in control group (n=47) were given BIPM, and those in research group (n=50) were treated with BIPM plus UTI. The clinical efficacy, adverse reactions, arterial blood gas (ABG) indices, PF and inflammatory cytokines were recorded. RESULTS: Patients in the research group had earlier fever clearance, inflammation absorption and cough disappearance than those in control group, as well as better clinical efficacy. In addition, no significant differences were found in the incidence of adverse reactions between the two groups during treatment. Monitoring changes in ABG indices, PF, and inflammatory cytokines revealed increased levels of PaO2, pH, FEV1, FVC, FEV1/FVC after treatment, but levels of PaCO2, IL-1ß, IL-6, TNF-α, and hs-CRP decreased compared to before treatment. Levels of indices that increased after treatment in the research group were higher than those in the control group, whereas the levels of other indices that decreased after treatment were lower. CONCLUSION: The combination of UTI and BIPM shortens the time of symptom disappearance, enhances PF, and inhibits inflammation, achieving higher efficacy in the treatment of severe pneumonia in the elderly.

Comparison of the antiviral effect of Arbidol and Chloroquine in treating COVID-19.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was broken out in December 2019 and soon became a global health emergency. Effective treatment for COVID-19 is urgently needed. In the present study, we aimed to evaluate the antiviral effect of Arbidol vs. Chloroquine in treating COVID-19. METHODS: We retrospectively analyzed 62 patients with COVID-19 diagnosed according to the guidelines for diagnosis and treatment of COVID-19 in China. They were divided into two groups depending on the antiviral drugs that they received. Participants in the Arbidol group (n=42) received 0.2 g Arbidol, tid for 10 days,and those in Chloroquine group (n=20) received 500 mg Chloroquine, bid for 10 days. The coronavirus negative conversion time and the length of hospital stay were analyzed and compared between the two groups. RESULTS: There was no significant difference in demographic and clinical characteristics between the two groups. After antiviral treatment, the nasopharyngeal specimen negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the length of hospital stay in the Arbidol group were significantly shorter than those in the Chloroquine group (18.50 vs. 25.05 days, P=0.001; 23.52 vs. 28.75 days, P=0.001). Adverse events observed during the antiviral treatment period were comparable between the two groups. Overall, 3 (7.14%) participants in the Arbidol group and 4 (20.0%) in the Chloroquine group experienced adverse events during antiviral treatment. CONCLUSIONS: These results suggest that Arbidol is advantageous over Chloroquine in terms of the SARS-CoV-2 negative conversion and the length of hospital stay in treating COVID-19 patients.

Genome evolution of blind subterranean mole rats: Adaptive peripatric versus sympatric speciation.

Speciation mechanisms remain controversial. Two speciation models occur in Israeli subterranean mole rats, genus Spalax: a regional speciation cline southward of four peripatric climatic chromosomal species and a local, geologic-edaphic, genic, and sympatric speciation. Here we highlight their genome evolution. The five species were separated into five genetic clusters by single nucleotide polymorphisms, copy number variations (CNVs), repeatome, and methylome in sympatry. The regional interspecific divergence correspond to Pleistocene climatic cycles. Climate warmings caused chromosomal speciation. Triple effective population size, Ne , declines match glacial cold cycles. Adaptive genes evolved under positive selection to underground stresses and to divergent climates, involving interspecies reproductive isolation. Genomic islands evolved mainly due to adaptive evolution involving ancient polymorphisms. Repeatome, including both CNV and LINE1 repetitive elements, separated the five species. Methylation in sympatry identified geologically chalk-basalt species that differentially affect thermoregulation, hypoxia, DNA repair, P53, and other pathways. Genome adaptive evolution highlights climatic and geologic-edaphic stress evolution and the two speciation models, peripatric and sympatric.

Predicative values of C-reactive protein for the therapeutic effects of ulinastatin combined with somatostatin in severe acute pancreatitis and for the severity of gastrointestinal failure.

Severe acute pancreatitis (SAP) is a serious systemic disease with high mortality. Ulinastatin is a drug widely used for patients with SAP and multiple organ failure syndrome. The present study aimed to investigate the capacity of the serum C-reactive protein (CRP) levels to predict the therapeutic effects of ulinastatin combined with somatostatin as well as determine the severity of SAP. SAP patients were treated with ulinastatin combined with somatostatin and serum CRP levels were measured. The computed tomography severity index (CTSI), acute physiology and chronic health evaluation II (APACHE II) and gastrointestinal failure scores were used to determine the therapeutic effects. All patients were assigned to the effective group and the ineffective group. Receiver operating characteristic curve analysis was performed to determine the sensitivity and specificity of CRP levels in predicting the severity of SAP and patient prognosis. Logistic regression analysis was adopted to investigate the factors influencing the therapeutic effects. Prior to and after treatment, serum CRP levels in patients of the effective and ineffective groups were significantly different. After treatment, serum CRP levels in patients of the effective group exhibited a more obvious reduction. The sensitivity and specificity of serum CRP levels in predicting the therapeutic effects of ulinastatin combined with somatostatin in SAP patients upon hospital admission were 0.813 and 0.934, respectively. Serum CRP levels were positively correlated with APACHE II, CTSI and gastrointestinal failure scores of SAP patients. The logistic regression demonstrated that serum albumin, creatinine and CRP levels on admission were factors influencing the therapeutic effects of ulinastatin combined with somatostatin in SAP patients. These results indicate that serum CRP levels may have a predictive value regarding the therapeutic effects of ulinastatin combined with somatostatin and are an indicator of the severity of gastrointestinal failure in SAP.

Physiological characteristics of Magnetospirillum gryphiswaldense MSR-1 that control cell growth under high-iron and low-oxygen conditions.

Magnetosome formation by Magnetospirillum gryphiswaldense MSR-1 is dependent on iron and oxygen levels. We used transcriptome to evaluate transcriptional profiles of magnetic and non-magnetic MSR-1 cells cultured under high-iron and low-iron conditions. A total of 80 differentially expressed genes (DEGs) were identified, including 53 upregulated and 27 downregulated under high-iron condition. These DEGs belonged to the functional categories of biological regulation, oxidation-reduction process, and ion binding and transport, and were involved in sulfur metabolism and cysteine/methionine metabolism. Comparison with our previous results from transcriptome data under oxygen-controlled conditions indicated that transcription of mam or mms was not regulated by oxygen or iron signals. 17 common DEGs in iron- and oxygen-transcriptomes were involved in energy production, iron transport, and iron metabolism. Some unknown-function DEGs participate in iron transport and metabolism, and some are potential biomarkers for identification of Magnetospirillum strains. IrrA and IrrB regulate iron transport in response to low-oxygen and high-iron signals, respectively. Six transcription factors were predicted to regulate DEGs. Fur and Crp particularly co-regulate DEGs in response to changes in iron or oxygen levels, in a proposed joint regulatory network of DEGs. Our findings provide new insights into biomineralization processes under high- vs. low-iron conditions in magnetotactic bacteria.

Transcriptome analysis reveals physiological characteristics required for magnetosome formation in Magnetospirillum gryphiswaldense MSR-1.

Magnetosome synthesis ability of Magnetospirillum gryphiswaldense MSR-1 in an autofermentor can be precisely controlled through strict control of dissolved oxygen concentration. In this study, using transcriptome data we discovered gene transcriptional differences and compared physiological characteristics of MSR-1 cells cultured under aerobic (high-oxygen) and micro-aerobic (low-oxygen) conditions. The results showed that 77 genes were up-regulated and 95 genes were down-regulated significantly under micro-aerobic situation. These genes were involved primarily in the categories of cell metabolism, transport, regulation and unknown-function proteins. The nutrient transport and physiological metabolism were slowed down under micro-aerobic condition, whereas dissimilatory denitrification pathways were activated and it may supplemental energy was made available for magnetosome synthesis. The result suggested that the genes of magnetosome membrane proteins (Mam and Mms) are not directly regulated by oxygen level, or are constitutively expressed. A proposed regulatory network of differentially expressed genes reflects the complexity of physiological metabolism in MSR-1, and suggests that some yet-unknown functional proteins play important roles such as ferric iron uptake and transport during magnetosome synthesis. The transcriptome data provides a holistic view of the responses of MSR-1 cells to differing oxygen levels. This approach will give new insights into general principles of magnetosome formation.

Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1.

We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and "domestication" by accelerated evolution of the strain upon repeated passaging.