Charting epimutation dynamics in human hematopoietic differentiation.

DNA methylation plays a critical role in hematopoietic differentiation. Epimutation is a stochastic variation in DNA methylation that induces epigenetic heterogeneity. However, the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain unclear. In this study, we developed a Julia package called EpiMut that enabled rapid and accurate quantification of epimutations. EpiMut was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature cells. We showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid lineages. Stepwise dynamics of epimutations were observed during the differentiation of each lineage. Importantly, we found that epimutation significantly enriched signals associated with lineage differentiation. Furthermore, epimutations in hematopoietic stem cells (HSCs) derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell disorders. Taken together, our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis, thereby offering insights into hematopoietic regulation.

Crystal structure, assembly process, and single-molecule magnet behavior of a triangular prismatic {Co9} cluster.

Using the polydentate ligand of H4L with the CoII ion, a triangular prism-type nine-nucleus cluster [Co9(L)3(CH2OCH2OH)6]·3.5H2O ({Co9}-Eg, H4L = 6,6'-(1H,1'H-[3,3'-bi(1,2,4-triazole)]-5,5'-diyl)dipicolinic acid) was constructed. Ion fragmentation during the formation of the {Co9}-Eg cluster was tracked using time-dependent electrospray ionization mass spectrometry. In addition, we proposed two possible formation processes (i) H4L → CoL → Co2L → Co6L3 → Co7L3 → Co9L3 and (ii) H4L → CoL → Co2L → Co3L → Co5L2 → Co7L3 → Co9L3. Magnetic studies show that {Co9}-Eg exhibits slow relaxation under a static zero field at low temperature, which is the main characteristic of single molecule magnets (SMMs).

Possible mechanisms of cholesterol elevation aggravating COVID-19.

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.

Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.

Hybrid MoS2/g-C3N4-assisted LDI mass spectrometry for rapid detection of small molecules and polyethylene glycols and direct determination of uric acid in complicated biological samples.

A novel matrix-assisted laser desorption/ionization time-of-flight mass spectrometric method (MALDI-TOF MS) for determination of highly sensitive small molecular compounds was developed based on molybdenum disulfide nanosheets hybridized with ultrathin graphitic carbon nitride (MoS2/g-C3N4) as the matrix. With this approach, the synergistic effects of MoS2 and g-C3N4 enhance the UV absorption of MoS2/g-C3N4, increase both desorption and ionization efficiency in LDI MS, and induce higher signal-to-noise ratio of analytes when compared with the bare MoS2 and g-C3N4 matrix in the determination of amino acids, antibiotics, neutral oligosaccharides, uric acid, and polyethylene glycols (PEGs). The detection limits of these small molecular compounds are in the ranges 0.1 to 10 µg mL-1, 1*10-3 to 1.0 µg mL-1, 1.0 to 10 µg mL-1, and 2*10-4 µg mL-1, respectively, and the polydispersity index of these PEGs is less than 1.02. Moreover, high salt tolera`nce and homogeneous deposition on the spot results in good reproducibility. The relative standard deviations (RSDs) of shot-to-shot and spot-to-spot (n = 15) of these compounds are less than 10.1% and 12.5%, respectively. With MoS2/g-C3N4, the uric acid in complicated biological samples can be directly determined in combination with LDI-TOF MS. We synthesized MoS2/g-C3N4 nanohybrid as an efficient matrix for MALDI-TOF MS analysis of small molecules as well as quantitative detection of uric acid in human urine.

Solvent effects on the structures and magnetic properties of two doubly interpenetrated metal-organic frameworks.

Two doubly interpenetrated coordination polymers [Co2(BDC)2(bpt)2]·nSolvent based on dimeric secondary building units and crystallizing with distinct solvent molecules (-H2O and -MeOH for nSolvent = 2H2O and MeOH·H2O, respectively) were obtained by employing 1,4-benzenedicarboxylate (BDC) and 1H-3,5-bis(4-pyridyl)-1,2,4-triazole) (bpt) as linkers. The structures consist of a square grid of dimers bridged by BDC and pillared by bpt. Thermogravimetry and PXRD indicate that the frameworks are stable and are retained up to 400 °C, but the structures are modified irreversibly. -H2O, high-symmetry Pna21, exhibits antiferromagnetic coupling within the dimer, while -MeOH, low-symmetry P21/n, exhibits ferromagnetic coupling. Upon desolvation, the -de and -de couplings are antiferromagnetic but reduced. Subsequent resolvation to -H2O and -MeOH resulted in a slight increase of the antiferromagnetic coupling without attaining the virgin states. The interesting difference of magnetic properties between -H2O and -MeOH, the solvated/desolvated phases, particularly at low temperature, indicates that there is a prominent solvent effect.

Samarium(III)-catalyzed C(sp3)-H bond activation: synthesis of indolizines via C-C and C-N coupling between 2-alkylazaarenes and propargylic alcohols.

A new rare earth metal and samarium-catalyzed C(sp(3))-H bond activation is reported in which 2-alkylazaarenes and propargylic alcohols were converted to indolizines. This process operates under mild conditions and solvent-free conditions. A broad scope of coupling partners has been established, and a likely mechanism has also been suggested.

Diaqua-bis(2,2'-biimidazole)cobalt(II) 4,4'-dicarboxy-biphenyl-3,3'-di-car-boxylate.

In the title compound, [Co(C(6)H(6)N(4))(2)(H(2)O)(2)](C(16)H(8)O(8)), the Co(II) cation and the organic anion occupy different crystallographic inversion centres and, as a consequence, the asymmetric unit comprises two half-mol-ecules. The benzene groups are coplanar. The four coordinating N atoms of the two bidentate biimidazole ligands define the equatorial plane of a slightly distorted octa-hedral CoO(2)N(4) geometry, and the water O atoms lie in the axial coordination sites. Translational (a,) and inversion-related symmetry operations link the Co complex mol-ecules and the negatively charged carboxyl-ate anions via inter-molecular N-H⋯O and O-H⋯O hydrogen bonds into sheets parallel to (01). The coordinated water mol-ecules connect the sheets through O-H⋯O hydrogen bonds, forming a three-dimensional framework. In addition, two intra-molecular O-H⋯O hydrogen bonds are observed between the carboxyl and carboxyl-ate groups.

Poly[(mu2-aqua-kappa2O:O)(mu3-azido-kappa3N1:N1:N3)(mu2-isonicotinato-kappa2O:O')lead(II)].

In the title compound, [Pb(C(6)H(4)NO(2))(N(3))(H(2)O)](n), the Pb ion is seven-coordinated by three N atoms from three azide ligands, two O atoms from two isonicotinate (inic) ligands and two O atoms from two coordinated water molecules, forming a distorted monocapped triangular prismatic coordination geometry. Each azide ligand bridges three Pb(II) ions in a mu(1,1,3) coordination mode to form a two-dimensional three-connected 6(3) topology network extending in the bc plane. The carboxylate group of the inic unit and the aqua ligand act as coligands to bridge Pb(II) ions. Adjacent two-dimensional layers are connected by hydrogen-bonding interactions between the isonicotinate N atom and the water molecule, resulting in an extended three-dimensional network. The title complex is the first reported coordination polymer involving a p-block metal, an azide and a carboxylate.