Comparative analysis of mitochondrial genome of a deepsea crab Chaceon granulates reveals positive selection and novel genetic features

Deep-sea organisms survive in an extremely harsh environment.There must be some genetic adaptation mechanisms for them.We systematically characterized and compared the complete mitochondrial genome(mitogenome)of a deep-sea crab(Chaceon granulates)with those of shallow crabs.The mitogenome of the crab was 16126 bp in length,and encoded 37 genes as most of a metazoan mitogenome,including 13 protein-coding genes(PCGs),22 transfer RNA(tRNA)genes,and 2 ribosomal RNA(rRNA)genes.The gene arrangement and orientation was conserved in the crabs.However,a unique mitogenome element regulator,the origin of light-strand replication(O L),was firstly predicted in the present crab mitogenome.In addition,further positive selection analysis showed that two residues(33 S in ND3 and 502 I in ND5)in C.granulates mitogenome were positively selected,indicated the selective evolution of the deep-sea crab.Therefore,the mitogenome of deep-sea C.granulates showed a unique OL element and positive selection.These special features would influence the mitochondrial energy metabolism,and be involved in the adaptation of deepsea environment,such as oxygen deficits and low temperatures.

Van der Waals Epitaxy of Anatase TiO2 on mica and Its Application as Buffer Layer

MICAtronics, based on the functional oxide/mica heterostructures, has recently attracted much attention due to its potential applications in transparent, flexible electronics and devices. However, the weak van der Waals interaction decreases the tolerable lattice mismatch and thus limits the species of function oxides that are able to be epitaxially grown on mica. We successfully fabricate relatively high-quality epitaxial anatase TiO2 thin films on mica substrates. Structural analyses reveal that the carefully chosen growth temperature(650℃) and suitable crystalline phase(anatase phase) of TiO2 are the key issues for this van der Waals epitaxy. Moreover, as a buffer layer, the TiO2 layer successfully suppresses the decomposition of BiFeO3 and the difficulty of epitaxial growth of BiFeO3 is decreased. Therefore, relatively high-quality anatase TiO2 is proved to be an effective buffer layer for fabricating more functional oxides on mica.

Regulation of heme biosynthesis and transport in metazoa

Heme is an iron-containing tetrapyrrole that plays a critical role in regulating a variety of biological processes including oxygen and electron transport, gas sensing, signal transduction, biological clock, and micro RNA processing. Most metazoan cells synthesize heme via a conserved pathway comprised of eight enzyme-catalyzed reactions. Heme can also be acquired from food or extracellular environment. Cellular heme homeostasis is maintained through the coordinated regulation of synthesis, transport, and degradation. This review presents the current knowledge of the synthesis and transport of heme in metazoans and highlights recent advances in the regulation of these pathways.

A systematic review of SARS-CoV-2 vaccine candidates

Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

Serum vitamin D content is associated with semen|parameters and serum testosterone levels in men

The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels.This is a crosssectional study conducted at Androscience,Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo,Brazil,with 508 male patients,aged 18-60 years,from 2007 to 2017.Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria.Patients were divided into normozoospermic group(NZG,n=124)and a group with seminal abnormalities(SAG,n=136).Evaluation included complete physical examination,past medical history,habits and lifestyle factors,two complete seminal analysis with sperm functional tests,serum levels of 25-hydroxy-vitamin D_(3)(25(OH)VD_(3)),total and free testosterone,luteinizing hormone(LH),follicle-stimulating hormone(FSH),sex hormone-binding globulin(SHBG),total cholesterol,homeostatic model assessment of insulin resistance(HOMA-IR)index,and karyotype.The mean concentration of 25(OH)VD_(3)was significantly lower in the SAG(P<0.001)and positively correlated with all baseline seminal parameters and total testosterone levels.In addition,serum vitamin D_(3)concentration was found to be positively correlated with sperm concentration(β=2.103;P<0.001),total number of spermatozoa with progressive motility(β=2.069;P=0.003),total number of motile spermatozoa(β=2.571;P=0.015),and strict morphology(β=0.056;P=0.006),regardless of other variables.This is the first comparative study to address the issue of serum vitamin D_(3)content between normozoospermic patients and those with sperm abnormalities.It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality,male reproductive potential,and testosterone levels.

Wearing Face Masks--the Simple and Effective Way to Block the Infection Source of COVID-19

The key difference between the coronavirus disease 2019(COVID-19)and previous coronaviruses such as SARS and MERS is that some infected people do not display obvious symptoms but are contagious during the incubation period for 14 days(1)or longer.Recently,there are many discussions about whether all persons should wear masks when they go out during the COVID-19 pandemic.The main reasons for the opposition are that the effectiveness of masks in preventing infection is not clear,ordinary people rarely wear masks correctly,everyone wearing masks may cause social panic,there are not enough masks,etc.(2–3).

Shear-wave velocity structures of the shallow crust beneath the Ordos and Sichuan Basins from multi-frequency direct P-wave amplitudes in receiver functions

As the two largest cratonic basins in China,the Ordos Basin and the Sichuan Basin are of key importance for understanding the evolutionary history of the Chinese continent.In this study,the shear-wave velocity(V_(S))structures of the shallow crust(depth up to 10 km)beneath the two basins are imaged based on the frequency-dependence of direct P-wave amplitudes in receiver functions.The teleseismic data used in the study came from 160 broadband seismic stations,including permanent and temporary stations.The results show that the V_(S) and the thickness of the sediments in the Ordos Basin and the Sichuan Basin are respectively lower and thicker in the west than in the east.In the Ordos Basin,the shallow crustal V_(S) increases gradually from 2.10 km s^(−1)in the northwest to 2.65 km s^(−1)in the southeast and the thickest sediments are 7–8 km in the northwest and 5 km in the east.In the Sichuan Basin,the shallow crustal V_(S) increases from 2.4 km s^(−1) in the west to 2.7 km s^(−1)in the east and the thickness of the sediments decreases from>7 km in the west to 6 km in the east.The east-west difference of the shallow crustal structures of the two basins may have been controlled by the Cenozoic India-Eurasia collision.The western parts of the basins near the collision have a higher deposition rate,while in the parts inside the basins far from the collision,the V_(S) slowly increases with depth,indicating that these areas have experienced a more uniform deposition process.In addition,both basins are characterized by velocity structures that are higher along the edges and lower inside of the basins.The edges of the basins suffered strong denudation due to the uplifting and deformation influenced by tectonic evolution.The downward gradient of the shear-wave velocity beneath the Ordos Basin is twice that of the Sichuan Basin,which may be caused by the different deposition and denudation rates of the two basins resulting from differences in structural evolution and thermal events.In addition,the northern Ordos Basin exhibits a strong structural horizontal stratification,while the southern part shows obvious lateral variations in the V_(S) structure,both of which may have been affected by the Qilian orogenic event,the collision and assembly of the South China and the North China block,and the lateral extrusion of the Tibetan Plateau.

The way of SARS-CoV-2 vaccine development:success and challenges

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide.With novel SARS-CoV-2 variants emerging and circulating widely,whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion.Moreover,some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity.Thus,in this review,we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern.We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials.Furthermore,we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines,such as special disease conditions,sex,and pre-existing immunity,with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.

Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)signaling.As an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling.However,the underlying molecular mechanism remains elusive.Here,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore targeting.Importantly,we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C.We further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore localization.Mechanistically,Mps1 C-terminal fragment mediates its dimerization.Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC function.Taken together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.

Viral infections and implications for male reproductive health

Viral infections have haunted humankind since times immemorial.Overpopulation,globalization,and extensive deforestation have created an ideal environment for a viral spread with unknown and multiple shedding routes.Many viruses can infect the male reproductive tract,with potential adverse consequences to male reproductive health,including infertility and cancer.Moreover,some genital tract viral infections can be sexually transmitted,potentially impacting the resulting offspring's health.We have summarized the evidence concerning the presence and adverse effects of the relevant viruses on the reproductive tract(mumps virus,human immunodeficiency virus,herpes virus,human papillomavirus,hepatitis B and C viruses,Ebola virus,Zika virus,influenza virus,and coronaviruses),their routes of infection,target organs and cells,prevalence and pattern of virus shedding in semen,as well as diagnosis/testing and treatment strategies.The pathophysiological understanding in the male genital tract is essential to assess its clinical impact on male reproductive health and guide future research.

DNA End Resection:Facts and Mechanisms

DNA double-strand breaks（DSBs）,which arise following exposure to a number of endogenous and exogenous agents,can be repaired by either the homologous recombination（HR）or non-homologous end-joining（NHEJ） pathways in eukaryotic cells.A vital step in HR repair is DNA end resection,which generates a long 30single-stranded DNA（ss DNA） tail that can invade the homologous DNA strand.The generation of 30 ss DNA is not only essential for HR repair,but also promotes activation of the ataxia telangiectasia and Rad3-related protein（ATR）.Multiple factors,including the MRN/X complex,C-terminal-binding protein interacting protein（Ct IP）/Sae2,exonuclease 1（EXO1）,Bloom syndrome protein（BLM）/Sgs1,DNA2 nuclease/helicase,and several chromatin remodelers,cooperate to complete the process of end resection.Here we review the basic machinery involved in DNA end resection in eukaryotic cells.

Clinical practice of emergency department-initiated extracorporeal cardiopulmonary resuscitation for cardiac arrest in adults

To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hospital cardiac arrest(OHCA)and in-hospital cardiac arrest(IHCA)were 140.7/100,000 and 10.2/1000,respectively.

Exploring potential of different X-ray imaging methods for early-stage lung cancer detection

Purpose To explore the potential of X-ray imaging for early-stage lung cancer screening and to help finding an optimal lung cancer screening method.Methods Experimentally and simulatively comparing performances of different X-ray techniques(absorption-contrast imaging and phase-contrast imaging)for model lung cancer samples.Results Absorption imaging shows performance equal to or better than that of low-radiation dose.Conclusion Absorption imaging is still the most promising imaging method for early lung cancer detection.

Cancer-associated adipocyte-derived G-CSF promotes breast cancer malignancy via Stat3 signaling

Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression,yet the underlying mechanisms and functional mediators remain elusive.We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes(CAAs)in vitro.The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing.One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor(G-CSF).Treatment with recombinant human G-CSF protein or stable expression of human G-CSF in triple-negative breast cancer(TNBC)cell lines enhanced epithelial–mesenchymal transition,migration,and invasion of cancer cells,by activating Stat3.Accordantly,targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody,a chemical inhibitor,or siRNAs for Stat3 could all abrogate CAA-or G-CSF-induced migration and invasion of breast cancer cells.The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells.Furthermore,in human breast cancer tissues,elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells.Together,our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAA-derived G-CSF.

Dynamin Regulates Autophagy by Modulating Lysosomal Function

Autophagy is a central lysosomal degradation pathway required for maintaining cellular homeostasis and its dysfunction is associated with numerous human diseases. To identify players in autophagy, we tested ~ 1200 chemically induced mutations on the X chromosome in Drosophila fat body clones and discovered that shibire （shi） plays an essential role in starvation-induced autophagy, shi encodes a dynamin protein required for fission of clathrin-coated vesicles from the plasma membrane during endocytosis. We showed that Shi is dispensable for autophagy initiation and autophagosome--lysosome fusion, but required for lysosomal/autolysosomal acidification. We also showed that other endocytic core machinery components like clathrin and AP2 play similar but not identical roles in regulating autophagy and lysosomal function as dynamin. Previous studies suggested that dynamin directly regulates autophagosome formation and autophagic lysosome reformation （ALR） through its excision activity, Here, we provide evidence that dynamin also regulates autophagy indirectly by regulating lysosomal function.