Proteins are responsible for the occurrence and treatment of many diseases, and therefore protein sequencing will revolutionize proteomics and clinical diagnostics. Biological nanopore approach has ...proved successful for single‐molecule DNA sequencing, which resolves the identities of 4 natural deoxyribonucleotides based on the current blockages and duration times of their translocations across the nanopore confinement. However, open challenges still remain for biological nanopores to sequentially identify each amino acid (AA) of single proteins due to the inherent complexity of 20 proteinogenic AAs in charges, volumes, hydrophobicity and structures. Herein, we focus on recent exciting advances in biological nanopores for single‐molecule protein sequencing (SMPS) from native protein unfolding, control of peptide translocation, AA identification to applications in disease detection.
Nanopore electrochemistry offers a bright prospect for single‐molecule protein sequencing by measuring specific interactions between amino acids based on their natural structure and chemistry continuity and diversity. This Minireview focusses on recent advances in biological nanopores from protein unfolding, peptide translocation, amino acid identification to diagnostic application.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Posttranslational modifications (PTMs) affect protein function/dysfunction, playing important roles in the occurrence and development of tauopathies including Alzheimer's disease. PTM detection is ...significant and still challenging due to the requirements of high sensitivity to identify the subtle structural differences between modifications. Herein, in terms of the unique geometry of the aerolysin (AeL) nanopore, we elaborately engineered a T232K AeL nanopore to detect the acetylation and phosphorylation of Tau segment (Pep). By replacing neutral threonine (T) with positively charged lysine (K) at the 232 sites, the T232K and K238 rings of this engineered T232K AeL nanopore corporately work together to enhance electrostatic trapping of the acetylated and phosphorylated Tau peptides. Translocation speed of the monophosphorylated Pep‐P was decelerated by up to 46 folds compared to the wild‐type (WT) AeL nanopore. The prolonged residences within the T232K AeL nanopore enabled to simultaneously identify the monoacetylated Pep‐Ac, monophosphorylated Pep‐P, di‐modified Pep‐P‐Ac and non‐modified Pep. The tremendous potential is demonstrated for PTM sensing by manipulating non‐covalent interactions between nanopores and single analytes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Sirtuins (SIRTs) are a class of lysine deacylases that regulate cellular metabolism and energy homeostasis. Although sirtuins have been proposed to function in nutrient sensing and signaling, the ...underlying mechanism remains elusive. SIRT7, a histone H3K18‐specific deacetylase, epigenetically controls mitochondria biogenesis, ribosomal biosynthesis, and DNA repair. Here, we report that SIRT7 is methylated at arginine 388 (R388), which inhibits its H3K18 deacetylase activity. Protein arginine methyltransferase 6 (PRMT6) directly interacts with and methylates SIRT7 at R388 in vitro and in vivo. R388 methylation suppresses the H3K18 deacetylase activity of SIRT7 without modulating its subcellular localization. PRMT6‐induced H3K18 hyperacetylation at SIRT7‐target gene promoter epigenetically promotes mitochondria biogenesis and maintains mitochondria respiration. Moreover, high glucose enhances R388 methylation in mouse fibroblasts and liver tissue. PRMT6 signals glucose availability to SIRT7 in an AMPK‐dependent manner. AMPK induces R388 hypomethylation by disrupting the association between PRMT6 and SIRT7. Together, PRMT6‐induced arginine methylation of SIRT7 coordinates glucose availability with mitochondria biogenesis to maintain energy homeostasis. Our study uncovers the regulatory role of SIRT7 arginine methylation in glucose sensing and mitochondria biogenesis.
Synopsis
PRMT6 methylates and thereby inhibits SIRT7, which epigenetically promotes mitochondria biogenesis and connects it to glucose availability in an AMPK‐dependent manner.
PRMT6 methylates SIRT7 at R388 to suppress its H3K18 deacetylase activity.
PRMT6 modulates SIRT7 methylation in an AMPK‐dependent manner.
SIRT7 methylation connects glucose sensing with mitochondria biogenesis.
PRMT6 methylates and thereby inhibits SIRT7, which epigenetically promotes mitochondria biogenesis and connects it to glucose availability in an AMPK‐dependent manner.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Our objective was to investigate the status and influence of myopia among primary school students in Fushun, Liaoning Province, China. We aimed to provide a theoretical and epistemological basis for ...implementing myopia prevention initiatives. We employed cluster sampling and surveyed 5216 primary school students from grades 1–6 across eight primary schools in Fushun City. Our participants included 2606 males and 2610 females whose average age was 9.25 (SD = 1.76) years. The rate of myopia among these primary school students was 29.54%, with statistically significant differences among students of different genders and grades. Logistic regression analysis further identified several possible protective factors, including appropriate reading distance, adequate home lighting, regular breaks between classes, conscientious eye exercises, and daily outdoor physical activity. Conversely, the associated risk factors were being female, being in a higher grade level, spending more than 4 hours on homework, occasionally reading while lying down, and having one or both parents with myopia. Overall, our results indicated a high incidence of myopia, highlighting the need for scientifically controlled interventions to manage and mitigate the occurrence and progression of myopia in this population.
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FSPLJ, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Three Gram-stain-positive, aerobic, motile actinobacterial strains designated as CPCC 205119
T
, CPCC 205215, and CPCC 205251 were isolated from different biological soil crust samples collected from ...Tengger Desert, China. The 16S rRNA gene sequence comparison of these three strains showed they had almost identical 16S rRNA genes, which were closely related to members of the family
Geodermatophilaceae
, with the highest similarities of 96.3–97.3% to the species of
Modestobacter
. In the phylogenetic tree based on 16S rRNA gene sequences, these isolates clustered into a subclade next to the branch containing the species of
Modestobacter lapidis
and
Modestobacter multiseptatus
, within the lineage of the genus
Modestobacter
. The comparative genomic characteristics (values of ANI, dDDH, AAI, and POCP) and the phenotypic properties (morphological, physiological, and chemotaxonomic characteristics) of these isolates readily supported to affiliate them to the genus
Modestobacter
as a single separate species. For which, we proposed that the isolates CPCC 205119
T
, CPCC 205215, and CPCC 205251 represent a novel species of the genus
Modestobacter
as
Modestobacter deserti
sp. nov. CPCC 205119
T
(=I12A-02624=NBRC 113528
T
=KCTC 49201
T
) is the type strain. The genome of strain CPCC 205119
T
consisted of one chromosome (4,843,235bp) containing 4,424 coding genes, 48 tRNA genes, five rRNA genes, three other ncRNA genes, and 101 pseudogenes, with G+C content of 74.7%. The whole-genome sequences analysis indicated that this species contained alkaline phosphatase genes (
phoA
/
phoD
), phosphate transport-related genes (
phoU
,
phnC
,
phnD
,
phnE
,
phoB
,
phoH
,
phoP
,
phoR
,
pitH
,
ppk
,
pstA
,
pstB
,
pstC
, and
pstS
), trehalose-phosphate synthase gene (
otsA
), trehalose 6-phosphate phosphatase gene (
otsB
) and other encoding genes for the properties that help the microorganisms to adapt to harsh environmental conditions prevalent in deserts. Strains of this species could solubilize tricalcium phosphate Ca
3
(PO
4
)
2
and phytin, assimilate pyrophosphate, thiophosphate, dithiophosphate, phosphoenol pyruvate, 2-deoxy-
d
-glucose-6-phosphate, and cysteamine-S-phosphate.
Human babesiosis is a worldwide disease caused by intraerythrocytic protozoa of the genus Babesia. It is transmitted by bites from ixodid ticks, and mechanically transmitted by blood transfusion. It ...is primarily treated with quinine and/or atovaquone, which are not readily available in China. In this study, we developed a novel treatment regimen involving doxycycline monotherapy in a patient with severe Babesia venatorum infection as an alternative therapeutic medication. The aim of our study is to provide a guidance for clinical practice treatment of human babesiosis.
A 73-year-old man who had undergone splenectomy and blood transfusion 8 years prior, presented with an unexplained fever, headache, and thrombocytopenia, and was admitted to the Fifth Medical Center of the PLA General Hospital. He was diagnosed with B. venatorum infection by morphological review of thin peripheral blood smears, which was confirmed by multi-gene polymerase chain reaction (PCR), and sequencing of the entire 18s rRNA and partial β-tubulin encoding genes, as well as isolation by animal inoculation. The doxycycline monotherapy regimen (peros, 0.1 g bisindie) was administered following pharmacological guidance and an effective outcome was observed. The patient recovered rapidly following the doxycycline monotherapy. The protozoan load in peripheral blood samples decreased by 88% in hematocrit counts after 8 days, and negative PCR results were obtained after 90 days of follow-up at the hospital. The treatment lasted for 3 months without any side effects or sequelae. The nine-month follow-up survey of the patient did not reveal any signs of recrudescence or anti-babesial tolerance.
We have reported a clinical case of successful doxycycline monotherapy for human babesiosis caused by B. venatorum, which provides an optional medical intervention for human babesiosis.
Several studies have demonstrated the effect of planting methods on rice yield, but information on the climate resources is limited. This study aims to reveal the effects of planting methods on ...climate resources associated with rice yield in a rice-wheat rotation system in the lower reaches of the Yangtze River, China. Field experiments were conducted in 2014 and 2015 with two japonica, two indica hybrid, and two japonica-indica hybrid varieties grown under three mechanized planting methods： carpet seedling of mechanical transplanting（CT）, mechanical direct seeding（DS）, and pot-hole seedling of mechanical transplanting（PT）. The rice yield and total dry matter under PT were greater than those under CT and DS methods. Besides, the entire growth duration and daily production showed significant positive relations with rice yield. Compared with CT and DS, the effective accumulated temperature and cumulative solar radiation of rice under PT were higher in phenological phases. In addition, the dry matter/effective accumulated temperature and solar energy utilization of rice under CT and DS were higher during vegetative phase and lower during reproductive and grain filling phases in contrast to PT. The mean daily temperature and mean daily solar radiation in the entire growth duration showed significant positive correlation with rice yield, total dry matter, and harvest index. This study demonstrated that when the mean daily temperature is 〈25.1°C in vegetative phase and 〉20.1°C in grain filling phase, rice yield could be increased by selecting mechanized planting methods. Most varieties under PT method exhibited high yield and climate resources use efficiency compared with CT and DS. In conclusion, the PT method could be a better cultivation measure for high rice yield, accompanied with high temperature and solar radiation use efficiency in a rice-wheat rotation system in the lower reaches of the Yangtze River, China.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic nephropathy. This study aimed to ...investigate the gut microbiota profiles and a group of targeted urine metabolic characteristics in T2DM patients with or without microalbuminuria, to determine the correlation between the gut microbiota composition, trimethylamine (TMA) metabolism, and the clinical features during progression of diabetic kidney disease (DKD).
This study included 26 T2DM patients with microalbuminuria (Micro), 26 T2DM patients with normoalbuminuria (Normo), and 15 healthy controls (HC). Urine and Fecal samples were detected using ultra performance liquid chromatography tandem mass spectrometry and 16S ribosomal DNA gene sequencing, respectively.
The TMAO/TMA ratio decreased gradually during the HC-Normo-Micro transition. The levels of TMA, choline and betaine were significantly different between the HC group and the T2DM patients belonging to both Normo and Micro groups. At the operational taxonomic unit (OTU) level, the gut microflora diversity was significantly reduced in the Micro groups compared to the HC groups and the Normo groups. Taxonomic analyses revealed significant consumption in the relative abundances of eight bacterial genera and significant enrichment of two bacterial genera during the HC-Normo-Micro transition. Furthermore, the relative abundances of six bacterial genera, namely, Ruminococcus_1, Eubacterium_ruminantium_group, Roseburia, Faecalibacterium, Fusicatenibacter and Coprococcus_3 exhibited significant differences, and were associated with elevated urinary albumin creatinine ratio (UACR), TMAO/TMA, TMA and its precursors in the Micro group compared with the other groups.
The imbalance of gut microbiota has occurred in patients with early-stage DKD, and the consumption of short-chain fatty acid-producing bacteria were associated with the accumulation of TMA and UACR.
To determine the effect of gender of reciprocal chromosomal translocation on blastocyst formation and pregnancy outcome in preimplantation genetic testing, including different parental ages.
This was ...a retrospective cohort study that enrolled 1034 couples undergoing preimplantation genetic testing-structural rearrangement on account of a carrier of reciprocal chromosomal translocation from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019. Group A represented 528 couples in which the man was the carrier of reciprocal translocation and group B represented 506 couples in which the woman was the carrier of reciprocal translocation. All patients were divided into two groups according to their age: female age<35 and female age≥35. Furthermore, the differences in blastocyst condition and pregnancy outcome between male and female carriers in each group were further explored according to their father's age.
The blastocyst formation rate of group A (55.3%) is higher than that of group B (50%) and the results were statistically significant (P<0.05). The blastocyst formation rate of group A is higher than that of group B, no matter in young maternal age or in advanced maternal age (P<0.05). The blastocyst formation rate in maternal age<35y and paternal age<30y in group A(57.1%) is higher than that of Group B(50%); Similarly, the blastocyst formation rate in maternal age≥35 and paternal age≥38y(66.7%) is higher than that of Group B(33.3%)(all P<0.05). There was no difference in fertilization rate, aeuploidy rate, clinical pregnancy rate, miscarriage rate and live birth rate between Group A and Group B.
When the carrier of reciprocal translocation is male, the blastocyst formation rate is higher than that of female carrier. While there is no significant difference between the two in terms of fertilization rate, aeuploidy rate, clinical pregnancy rate, miscarriage rate and live birth rate.
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