Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon.

Retroelements are the widespread jumping elements considered as major drivers for genome evolution, which can also be repurposed as gene-editing tools. Here, we determine the cryo-EM structures of eukaryotic R2 retrotransposon with ribosomal DNA target and regulatory RNAs. Combined with biochemical and sequencing analysis, we reveal two essential DNA regions, Drr and Dcr, required for recognition and cleavage. The association of 3' regulatory RNA with R2 protein accelerates the first-strand cleavage, blocks the second-strand cleavage, and initiates the reverse transcription starting from the 3'-tail. Removing 3' regulatory RNA by reverse transcription allows the association of 5' regulatory RNA and initiates the second-strand cleavage. Taken together, our work explains the DNA recognition and RNA supervised sequential retrotransposition mechanisms by R2 machinery, providing insights into the retrotransposon and application reprogramming.

Novel compound heterozygous mutations in DNAH1 cause primary infertility in Han Chinese males with multiple morphological abnormalities of the sperm flagella.

This study aimed to identify genetic causes responsible for multiple morphological abnormalities of the sperm flagella (MMAF) in the Han Chinese population. Three primary infertile males with completely immobile sperm and MMAF were enrolled. Whole-exome sequencing and Sanger sequencing were performed to identify disease-causing genes. Subsequently, morphological and ultrastructural analyses of sperm flagella were investigated. The probable impact of genetic variants on protein function was analyzed by online bioinformatic tools and immunofluorescence assay. Three patients with dynein axonemal heavy chain 1 (DNAH1) gene compound heterozygous variations were identified. DNAH1 c.7435C>T, p.R2479X and c.10757T>C, p.F3586S were identified in the patient from Family 1, c.11726_11727delCT, p.P3909fs and c.12154delC, p.L4052fs were found in the patient from Family 2, and c.10627-3C>G and c.11726_11727delCT, p.P3909fs existed in the patient from Family 3. Four of these variations have not been reported, and all the mutations showed pathogenicity by functional effect predictions. The absence of the center pair and disorganization of the fibrous sheath were present in sperm flagella at the ultrastructural level. Moreover, the expression of DNAH1 was absent in spermatozoa from the participants, validating the pathogenicity of the variants. All three couples have undergone intracytoplasmic sperm injection (ICSI), and two couples of them became pregnant after the treatment. In conclusion, the newly identified DNAH1 mutations can expand the mutational and phenotypic spectrum of MMAF genes and provide a theoretical basis for genetic diagnosis in MMAF patients. It is recommended to conduct genetic screening in male infertility patients with MMAF and provide rational genetic counseling, and ICSI might be an optimal strategy to help with fertilization and conception for patients with DNAH1 mutations.

Risk of birth defects in children conceived by artificial oocyte activation and intracytoplasmic sperm injection: a meta-analysis.

BACKGROUND: Whether artificial oocyte activation (ICSI-AOA) will increase the risk of birth defects remains controversial. Thus, we performed this study to evaluate the risk of birth defects and further compare the incidence of different birth defects types (chromosomal aberrations and non-chromosomal aberrations) in children conceived by ICSI-AOA and conventional intracytoplasmic sperm injection (ICSI) in an enlarged sample size. METHOD: A comprehensive review of the literatures comparing birth defects in children conceived by ICSI-AOA and conventional ICSI by October 2020 was performed in PubMed, Embase, Cochrane Libraries, Web of Science, and Chinese databases including China National Knowledge Infrastructure, China Biology Medicine disc and Wan Fang. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. RESULTS: Five studies were included in the final analysis. Compared with conventional ICSI, ICSI-AOA did not increase the birth defects rate (RR = 1.27, 95%CI 0.70-2.28) of children. Furthermore, in a subgroup analysis, birth defects were classified into two types (chromosomal aberrations and non-chromosomal aberrations) in four studies and no statistical difference were revealed. CONCLUSION: Our analysis indicates that ICSI-AOA represents no significant difference in the prevalence of major birth defects or types of birth defects (chromosomal aberrations and non-chromosomal aberrations) comparing with conventional ICSI. This conclusion may provide clinicians evidence-based support in patient counseling and instruction of the application and safety concern about ICSI-AOA.

Sepsis as an important risk factor for gastrointestinal bleeding in acute coronary syndrome patients: Two case reports.

RATIONALE: Sepsis is a common stressor that may decrease microcirculation in the gastrointestinal tract in patients and increase the gastrointestinal bleeding risk of stress-related mucosal disease. However, the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines) bleeding risk score, recommended by authoritative guidelines for acute coronary syndrome (ACS), does not include sepsis as a bleeding risk factor. PATIENT CONCERNS: The 2 cases were about ACS with hemorrhagic complications. The first patient was an 88-year-old man with hypertension, gallstones, hepatic cysts, and chest pain; the second one was a 79-year-old man with chest pain and hypertension. These 2 ACS patients had no bleeding on admission; however, both patients suffered apparent gastrointestinal bleeding immediately after the development of sepsis or severe sepsis. DIAGNOSES: Both patients were diagnosed as ACS with sepsis. INTERVENTIONS: The first ACS patient had no use of proton pump inhibitors (PPIs) for prophylaxis prior to the diagnosis of sepsis. The second one was administered PPIs at standard oral doses. OUTCOMES: The first patient suffered from gastrointestinal bleeding immediately after the onset of sepsis. And oral PPIs failed to prevent upper gastrointestinal bleeding for the second patient, when severe sepsis developed. However, the second patient's gastrointestinal hemorrhage gradually stopped immediately after high doses of PPIs were administered intravenously, rather than orally. When sepsis developed again, the second patient also had no recurrent gastrointestinal bleeding under the protection of PPIs at standard oral doses. LESSONS: Our report suggests that sepsis may be an important bleeding risk factor for ACS patients, and the reasonable use of PPIs to prevent gastrointestinal bleeding could be vital for ACS patients complicated with sepsis.

Effects of Ginsenoside Rg3 on fatigue resistance and SIRT1 in aged rats.

BACKGROUND: Ginsenoside Rg3 (Rg3) is one of the key components of a frequently used herbal tonic panax ginseng for fatigue treatment. However, the molecular mechanisms of Rg3 on anti-fatigue effects have not been completely understood yet. METHODS AND MATERIALS: We built a postoperative fatigue syndrome (POFS) model and tried to elucidate the molecular mechanisms responsible for anti-fatigue effects of Rg3. 160 aged male rats were randomly divided into four groups (n = 40/group): normal group, Rg3-treated normal group (Rg3 group), postoperative fatigue syndrome model group (POFS group) and Rg3-treated postoperative fatigue syndrome model group (POFS + Rg3 group). The open field test (OFT) was used to assess general activity and exploratory behavior of rats in different groups. We then analyzed total cholesterol (TC), serum triglyceride (TG) and lactate dehydrogenase (LDH) in the blood, as well as superoxide dismutase (SOD), malondialdehyde (MDA), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in skeletal muscles of rats. We also detected the influence of Rg3 on silent information regulator of transcription 1 (sirtuin1, SIRT1) activity and protein 53 (p53) transcriptional activity in vitro. RESULTS: Rg3 significantly increased the journey distance and rearing frequency, while slowed down the rest time. The serum concentrations of TC, TG and LDH were all up-regulated by Rg3. Meanwhile, Rg3 increased concentrations of SOD, but also decreased MDA release out of skeletal muscles. The mRNA expressions of PGC-1α and PEPCK were also enhanced by Rg3. Besides, Rg3 could activate SIRT1 and suppress p53 transcriptional activity in the biological process. DISCUSSION AND CONCLUSION: Rg3 could improve exercise performance and resist fatigue possibly through elevating SIRT1 deacetylase activity.

Current strategies to improve the safety of chimeric antigen receptor (CAR) modified T cells.

Adoptive immunotherapy adopting chimeric antigen receptor (CAR) modified T cells has arisen attention as a hard-hitting therapy for numerous cancers. CARs are genetically engineered receptors that could stimulate tumor cytotoxicity once binding to the specific tumor epitopes. In spite of current noteworthy achievements in hematologic malignancies, the safety problems have aroused public awareness. In this review, we will focus on recent potential strategies to improve the security of CAR modified T cells.

Acquired pure red cell aplasia due to treatment with clopidogrel: first case report.

A 62-year-old woman with hypertension, type 2 diabetes mellitus, hyperlipemia and coronary heart disease started taking clopidogrel, with no addition of any other new drugs. However, with the addition of the drug, the patient was diagnosed as having acquired pure red cell aplasia (PRCA), and no any other inducing factors were detected from the patient. Furthermore, with the withdrawal of clopidogrel from the treatment, the patient recovered from the PRCA and did not recur. Therefore, we report PRCA as a rare side effect of clopidogrel for the first time.

[Structural and spectral study of a novel rare-earth and 3-bi-pyridine acid polymer].

A novel zero-dimension coordination polymer Gd2 (In)6 (H2O)4 (1) (In = 3-bipyridine acid) was synthesized under hydrothermal condition. By the analysis of single-crystal X-ray diffraction, the structure of the compound is that two Gd atoms connect with zero-dimension bi- nucleus cluster by the bridged carboxylate of four Ins. Based on the determination of the structure, the 2D correlation FTIR spectra with the perturbations of magnetism and thermal was applied. Under the perturbations of temperature, the vibration of the carboxylate has the very strong response, which is related with the strong coordinating ability of the carboxylate. At the same time, due to the different coordinated mode of the carboxylate with Gd, the response of Gd--O bonds is different under the temperature perturbations. Under the perturbations of magnetism, the vibration of the carboxylate has also the very strong response, which may be related with one-negetive charge of the carboxylate. The 2D correlation ultraviolet spectral with the perturbation of magnetism were investigated. Compared with one-dimension ultraviolet spectral, the transition of the pi electrons in bi-pyridine ring and the charge transition from ligand to the metal have the very strong response. At the same time, the fluorescence spectral and TGA were studied.

[2D correlation spectral study of a coordination polymer [Eu(PCPOA)3 (H2O)]n].

A novel two dimensional coordination polymer [Eu(PCPOA)3 (H2O)], was synthesized under hydrothermal condition. Based on the determination of the structure, the 2D correlation FTIR spectra with the perturbation of magnetism and the 2D correlation fluorescence spectra with the perturbation of temperature were investigated. The energy bonds were calculated using CASTEP Program of Material studio. The Europium ions are nine-coordinated and the ligands adopted two different modes to connect the Eu3+ ions to 2D layer structure. The study of the 2D-FTIR reveals that the carboxylates coordinate with the center ions not only as monodentate, but also as bidentate chelate. The 2D fluorescence spectra indicates that the transition of (5)D0-->(7)F2 is influenced intensively by the perturbation of temperature.

[Spectral study of two compounds of molybdate salt with beta-[Mo8O26] anion].

Two compounds of organic molybdate-alkali salt: [H(4,4'-bipy)]2[K2Mo8O26](I) and H3 [Na Mo8 O26] (4,4'-bipy)5 (H2O)4 (II), with beta-[Mo8O26]4- anion, were synthesized. The relationship between their properties and structures was studied by using FTIR, Raman, NIR-Vis and fluorescence etc. They possess isolating beta-[Mo8O26]4- anion, whose terminal O atoms combine with alkali. The FTIR and Raman spectra showed that the vibrational frequencies of the group are related to the structure of the materials. In UV-Vis spectra of compound (I) and (II), there is a characteristic wide peak at 280-300 nm. The fluorescence spectra of compound (I) and (II) were studied, which showed that the wide emission peak is from 450 to 650 nm and excited by 350 nm for compound (I), and the emission peak is from 400 to 550 nm and excited by 325 nm for compound (II). For compound (I), the intensity of emission becomes stronger with decreasing of temperature, and so does the fluorescence lifetime.

Barium divanadium(V) tellurite(IV).

A new three-dimensional bimetallic tellurite, BaV2TeO8, was synthesized by the hydrothermal reaction of Ba(OH)2, TeO2 and V2O5, and characterized by single-crystal X-ray diffraction. The three-dimensional framework is built up from anionic [V2TeO8]n(2n-) layers parallel to (101) and connected via Ba-O bonds. The anionic layers are formed by three types of polyhedra, namely VO5 tetragonal pyramids, VO(4) tetrahedra and TeO(4+2) 'folded square' polyhedra.

[Hydrothermal synthesis and spectra properties of compound Mn5(PO3(OH))2(PO4)2(H2O)4].

The title compound Mn5(PO3(OH))2(PO4)2(H2O)4 was synthesized under hydrothermal condition. Its crystal structure was determined by single-crystal X-ray diffraction. DRS, IR, fluorescence and TGA spectra were used to characterize the title compound. As a result, the compound is formed by linking with PO4 and MnO6, and the oxygen in it can be divided to three categories, so in IR spectra the characteristic peaks of Mn-O and P-O are separated in to three, respectively. In DRS there aretwo peaks at 210 and 250 nm coresponding Od-->Mn and Ob,c-->Mn. In fluorescence spectra the emission peaks are located at 354 and 413 nm when excited at 218 and 310 nm. Besides, thermal behavior of the compound is discussed by TGA diagrams. Finally, quantum chemistry calculation is performed to explain the structure characteristic. HF = -4558.6595551 a.u., HOMO(Alpha) = - 0.280 80a. u, LOMO(Alpha) = 0.01527 a.u., deltaE(Alpha) = 0.29607 a.u.; HOMO(Beta) = -0.25919 a.u., LOMO(Beta) = 0.00108 a.u., deltaE(Beta) = 0.260 72 a.u. and Dipole = 4.2082 Debye.

[Synthesis and spectroscopic studies of supermolecules of PW(x)V(12 - x)-MV].

A series of supermolecules of PW(x)V(12 - x)-MV (PW(x)V(12 - x): polyoxometalates x = 2, 4, 6, 8, 10; MV: methyl violet) with Keggin structure were prepared and their characters were studied by electronic spectra, infrared spectra and fluorescence spectra. As a result, the supermolecules were formed by the cooperating action between polyoxometalates and methyl violet. In the supermolecule, the structures of cation and anion are not destroyed. With the content of V increasing, the oxidation ability of polyoxometalates anion is enhanced, and the interaction of methyl violet cation and polyoxometalates anion is enhanced too. The FTIR absorption peaks of nu(as)(M=O(t)), nu(as)(M-O(b)-M) and nu(as)(M-O(c)-M) move from 966, 886, and 804 cm(-1) to 955, 875 and 786 cm(-1), respectively; the UV-Vis absorption peak moves from 519 to 506 nm; the emission peak excited at 530 nm moves from 692 to 644 nm too. These changes are according with the degree of the interaction of polyoxometalates and methyl violet.

[Spectral study of the compound Zn(Pht):0.05 Sm].

Zn(Pht):0.05 Sm compounds have been synthesized by microwave. The compound was characterized by XRD, FTIR, NIR FT-Raman, DRS UV/Vis, fluorescence spectra, and TG analysis. FTIR and FT-Raman indicated that each of the carbonyl group in the phthalate of the compound combined with metal zinc as mono-dentate terminal chelating. Compared with Pht, the title compound's pi-->pi* from phthalate shifted from 255 and 289 nm to 235 and 270 nm, respectively. In the fluorescence spectra, there are emission peaks at 560, 596, 642 and 670 nm when excited by 240 nm, which correspond to the transitions from Sm3+'s emission states of 4G(5/2), 6H(7/2), 6H(9/2) and 6H(11/2) to the ground state. As a result, Zn(Pht) improves the emission efficiency of Sm3+ notably. At the emission peak of 596 and 642 nm when excited by 240 nm, the fluorescence lifetime of the compound is tau1 = 1.57 ns and tau2 = 76.94 ns, and tau1 = 1.19 ns and tau2 = 55.64 ns, respectively. TGA showed that the title compound begins to decompose at 380 degrees C, while it is stable below 380 degrees C.

[Spectral study of three compounds of tungstosilicic salt with Keggin structure].

Three compounds of tungstosilicic acid and tungstosilicic salt: K3H[SiW(VI)12O40].3H2O(I), (H3O)4[H3SiW(VI)9W(V)3O40].2H2O(II) and [(CH3)4N]4[SiW(VI)12O40].4.5H2O(III), with Keggin structure, have been synthesized. The relationship between their properties and structures was studied by using FTIR, NIR FT-Raman, UV-Vis and flurescence etc. They possess isolated [SiW12O40] cage anion, which combines with cation and water by static electric action and weak hydrogen bond; The study of their FTIR and Raman spectra shows that the vibrational frequencies of the group are related to the structure of the materials. For the compound II, the vibrational frequency of vas(W=Od) decreases as part of W6+ are reduced to W5+, and the charges of anion group affect vas(W-Oc-W), vas(Si-Oa) and delta(Oa-Si-Oa) etc. apparently. In UV-Vis spectra of compound I and II, there are two characteristic peaks at 200 and 260 nm, respectively. The fluorescence spectra of compound I were studied, and showed that the emission peak is at 350, 440, 520 and 675 nm excited by 220, 350 and 440 nm.

[Spectral study of the compounds with [(PO4)2Mo5O15]].

Three novel organic-molybdenum phosphates with [(PO4)2Mo5O15], namely (NH3CH2CH2NH3)2.5[(PO4)(HPO4) Mo5O15].7.5H2O (I), (H3NCH2CH2NH3)3.[(PO4)2Mo5O15].3H2O (II) and (H3NCH2CH2NH3)2.[Cu(en)] [(PO4)2Mo5O15].5H2O (III), were synthesized. The relationship between their properties and structures were studied by using FTIR, NIR-Raman, UV-Vis DRS and fluorescence spectra. Among these compounds, compound I and II possess isolating [(PO4)2Mo5O15] cage, while compound III is rather novel whose [(PO4)2Mo5O15] cages are bridging into chains by [Cuen] groups. The characteristic vibrational frequencies of molybdenum phosphates are related to the structures of these compounds. In the UV-Vis DRS spectra, there are two characteristic peaks of heteropoly compounds at 200 and 260 nm. The fluorescence spectra of these three compounds have been studied, which have emission peaks at about 400 nm excited by 240 nm, which are caused by O mu-Mo, while compound III produces 604 nm emission excited by 570 nm, which is caused by the LMCT of [Cuen] group.