Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors.

Hematopoietic stem cells (HSCs) sustain blood formation throughout life and are the functional units of bone marrow transplantation. We show that transient expression of six transcription factors Run1t1, Hlf, Lmo2, Prdm5, Pbx1, and Zfp37 imparts multilineage transplantation potential onto otherwise committed lymphoid and myeloid progenitors and myeloid effector cells. Inclusion of Mycn and Meis1 and use of polycistronic viruses increase reprogramming efficacy. The reprogrammed cells, designated induced-HSCs (iHSCs), possess clonal multilineage differentiation potential, reconstitute stem/progenitor compartments, and are serially transplantable. Single-cell analysis revealed that iHSCs derived under optimal conditions exhibit a gene expression profile that is highly similar to endogenous HSCs. These findings demonstrate that expression of a set of defined factors is sufficient to activate the gene networks governing HSC functional identity in committed blood cells. Our results raise the prospect that blood cell reprogramming may be a strategy for derivation of transplantable stem cells for clinical application.

DNA-damage-induced differentiation in hematopoietic stem cells.

Aging of hematopoietic stem cells (HSCs) is accompanied by diminished functional potential. Wang et al. now provide evidence for an HSC-specific differentiation checkpoint mediated by the transcription factor BATF, which limits self-renewal of HSCs in response to the accumulation of DNA damage.

Recent advances in the biosensors application for reviving infectious disease management in silkworm model: a new way to combat microbial pathogens.

Silkworms are an essential economic insect but are susceptible to diseases during rearing, leading to yearly losses in cocoon production. While chemical control is currently the primary method to reduce disease incidences, its frequent use can result in loss of susceptibility to pathogens and, ultimately, antibiotic resistance. To effectively prevent or control disease, growers must accurately, sensitively, and quickly detect causal pathogens to determine the best management strategies. Accurate recognition of diseased silkworms can prevent pathogen transmission and reduce cocoon loss. Different pathogen detection methods have been developed to achieve this objective, but they need more precision, specificity, consistency, and promptness and are generally unsuitable for in-situ analysis. Therefore, detecting silkworm diseases under rearing conditions is still an unsolved problem. As a consequence of this, there is an enormous interest in the development of biosensing systems for the early and precise identification of pathogens. There is also significant room for improvement in translating novel biosensor techniques to identify silkworm pathogens. This study explores the types of silkworm diseases, their symptoms, and their causal microorganisms. Moreover, we compare the traditional approaches used in silkworm disease diagnostics along with the latest sensing technologies, with a precise emphasis on lateral flow assay-based biosensors that can detect and manage silkworm pathogens.

Emissive Dark Excitons in Monoclinic Two-Dimensional Hybrid Lead Iodide Perovskites.

Typically, bright excitons (XB) emit light in two-dimensional (2D) layered hybrid perovskites. There are also dark excitons (XD), for which radiative recombination is spin-forbidden. Application of a magnetic field can somewhat relax the spin-rule, yielding XD emission. Can we obtain XD light emission in the absence of a magnetic field? Indeed, we observe unusually intense XD emission at ∼7 K for (Rac-MBA)2PbI4, (Rac-4-Br-MBA)2PbI4, and (R-4-Br-MBA)2PbI4 (Rac-MBA: racemic methylbenzylammonium), which crystallize in a lower symmetry monoclinic phase. For comparison, orthorhombic (R-MBA)2PbI4 does not exhibit XD emission. XD has a lower energy than XB, with energy difference ΔE. In monoclinic samples, ΔE ∼ 20 meV is large enough to suppress the thermal excitation of XD to XB, at temperatures <30 K. Consequently, XD recombines by emitting light with a long lifetime (∼205 ns). At higher temperatures, the emission switches to the spin-allowed XB (lifetime < 1 ns).

Rational Design of Non-Centrosymmetric Hybrid Halide Perovskites.

Structural non-centrosymmetry in semiconducting organic-inorganic hybrid halide perovskites can introduce functionalities like anomalous photovoltaics and nonlinear optical properties. Here we introduce a design principle to prepare Pb- and Bi-based two- and one-dimensional hybrid perovskites with polar non-centrosymmetric space groups. The design principle relies on creating dissimilar hydrogen and halogen bonding non-covalent interactions at the organic-inorganic interface. For example, in organic cations like I-(CH2)3-NH2(CH3)+ (MIPA), -CH3 is substituted by -CH2I at one end, and -NH3+ is substituted by -NH2(CH3)+ at the other end. These substitutions of two -H atoms by -I and -CH3 reduce the rotational symmetry of MIPA at both ends, compared to an unsubstituted cation, for example, H3C-(CH2)3-NH3+. Consequently, the dissimilar hydrogen-iodine and iodine-iodine interactions at the organic-inorganic interface of (MIPA)2PbI4 2D perovskites break the local inversion symmetries of Pb-I octahedra. Owing to this non-centrosymmetry, (MIPA)2PbI4 displays visible to infrared tunable nonlinear optical properties with second and third harmonic generation susceptibility values of 5.73 pm V-1 and 3.45 × 10-18 m2 V-2, respectively. Also, the single crystal shows photocurrent on shining visible light at no external bias, exhibiting anomalous photovoltaic effect arising from the structural asymmetry. The design strategy was extended to synthesize four new non-centrosymmetric hybrid perovskite compounds. Among them, one-dimensional (H3N-(CH2)3-NH(CH3)2)BiI5 shows a second harmonic generation susceptibility of 7.3 pm V-1 and a high anomalous photovoltaic open-circuit voltage of 22.6 V.

Anion Tuned Structural Modulation and Nonlinear Optical Effects of Metal-Ion Directed 310 -Helix Networks.

Metals play an important role in the structure and functions of various proteins. The combination of metal ions and peptides have been emerging as an attractive field to create advanced structures and biomaterials. Here, we are reporting the anion-influenced, silver ion coordinated diverse networks of designed short tripeptide 310 -helices with terminal pyridyl groups. The short peptides adopted classical right-handed, left-handed and 310 EL -helical conformations in the presence of different silver salts. The peptides have displayed conformational flexibility to accommodate different sizes and interactions of anions to yield a variety of metal-coordinated networks. The complexes of metal ions and peptides have shown different porous networks, right- and left-handed helical polymers, transformation of helix into superhelix and 2 : 2 metal-peptide macrocycles. Further, the metal-peptide crystals with inherent dipoles of helical peptides gave striking second harmonic generation response. The optical energy upconversion from NIR to red and green light is demonstrated. Overall, we have shown the utilization of short 310 -helices for the construction of diverse metal-coordinated helical networks and notable non-linear optical effects.

DNA damage response in adult stem cells: pathways and consequences.

In contrast to postmitotic or short-lived somatic cells, tissue-specific stem cells must persist and function throughout life to ensure tissue homeostasis and repair. The enormous functional demands and longevity of stem cells raises the possibility that stem cells might be uniquely equipped to maintain genomic integrity in ways different than somatic cells. Indeed, evidence suggests that stem cell compartments possess unique properties that combine to either limit or, in some instances, accelerate DNA damage accrual.

Finite Field Transport Response of a Dilute Magnetic Topological Insulator-Based Josephson Junction.

Hybrid samples combining superconductors with magnetic topological insulators are a promising platform for exploring exotic new transport physics. We examine a Josephson junction of such a system based on the dilute magnetic topological insulator (Hg,Mn)Te and the type II superconductor MoRe. In the zero and very low field limits, to the best of our knowledge, the device shows, for the first time, an induced supercurrent through a magnetically doped semiconductor, in this case, a topological insulator. At higher fields, a rich and hysteretic magnetoresistance is revealed. Careful analysis shows that the explanation of this behavior can be found in magnetic flux focusing stemming from the Meissner effect in the superconductor, without invoking any role of proximity-induced superconductivity. The phenomena is important because it will ubiquitously coexist with any exotic new physics that may be present in this class of devices.

Introducing Intermolecular Cation-π Interactions for Water-Stable Low Dimensional Hybrid Lead Halide Perovskites.

Optoelectronically active hybrid lead halide perovskites dissociate in water. To prevent this dissociation, here, we introduce long-range intermolecular cation-π interactions between A-site cations of hybrid perovskites. An aromatic diamine like 4,4'-trimethylenedipyridine, if protonated, can show a long-range cation-π stacking, and therefore, serves as our A-site cation. Consequently, 4,4'-trimethylenedipyridinium lead bromide [(4,4'-TMDP)Pb2 Br6 ], a one-dimensional hybrid perovskite, remains completely stable after continuous water treatment for six months. Mechanistic insights about the cation-π interactions are obtained by single-crystal X-ray diffraction and nuclear magnetic resonance spectroscopy. The concept of long-range cation-π interaction is further extended to another A-site cation 4,4'-ethylenedipyridinium ion (4,4'-EDP), forming water-stable (4,4'-EDP)Pb2 Br6 perovskite. These water-stable perovskites are then used to fabricate white light-emitting diode and for light up-conversion through tunable third-harmonic generation. Note that the achieved water stability is the intrinsic stability of perovskite composition, unlike the prior approach of encapsulating the unstable perovskite material (or device) by water-resistant materials. The introduced cation-π interactions can be a breakthrough strategy in designing many more compositions of water-stable low-dimensional hybrid perovskites.

Psychological distress in Nepalese residents during COVID-19 pandemic: a community level survey.

BACKGROUND: COVID-19 pandemic has created unprecedented health and economic impact. Psychological stress, anxiety and depression are affecting not only COVID-19 patients but also health professionals, and general population. Fear of contracting COVID-19, forced restrictive social measures, and economic hardship are causing mental trauma. Nepal is a developing country from South Asia where the COVID-19 pandemic is still evolving. This online survey has been carried out to understand impact of COVID- 19 on mental health of Nepalese community dwellers. METHODS: The COVID-19 Peritraumatic Distress Index (CPDI) questionnaire adapted from the Shanghai Mental Health Centre was used for online data collection from 11 April-17 May 2020. Collected data were extracted to Microsoft excel-13 and imported and analyzed using SPSS (Statistical Package for Social Sciences) version-22. An initial univariate analysis was conducted for all variables to assess the distribution. Logistic regression analyses were done to estimate the odds ratios of relevant predicting variables. RESULTS: A total of 410 participants completed the self-rated questionnaires. Mean age of study participants was 34.8 ± 11.7 years with male preponderance. 88.5% of the respondents were not in distress (score less than 28) while, 11% had mild to moderate distress and 0.5% had severe distress. The prevalence of distress is higher among age group > 45 years, female gender, and post-secondary education group. Health professional were more likely to get distressed. Respondents with post-secondary education had higher odds (OR = 3.32; p = 0.020) of developing distress as compared to respondents with secondary education or lower. CONCLUSION: There is lower rate of psychological distress in city dwellers and people with low education. Adequate intervention and evaluation into mental health awareness, and psychosocial support focused primarily on health care workers, female and elderly individuals is necessary.

Ultralow Thermal Conductivity in Chain-like TlSe Due to Inherent Tl+ Rattling.

Understanding the mechanism that correlates phonon transport with chemical bonding and solid-state structure is the key to envisage and develop materials with ultralow thermal conductivity, which are essential for efficient thermoelectrics and thermal barrier coatings. We synthesized thallium selenide (TlSe), which is comprised of intertwined stiff and weakly bonded substructures and exhibits intrinsically ultralow lattice thermal conductivity (κL) of 0.62-0.4 W/mK in the range 295-525 K. Ultralow κL of TlSe is a result of its low energy optical phonon modes which strongly interact with the heat carrying acoustic phonons. Low energy optical phonons of TlSe are associated with the intrinsic rattler-like vibration of Tl+ cations in the cage constructed by the chains of (TlSe2)nn-, as evident in low temperature heat capacity, terahertz time-domain spectroscopy, and temperature dependent Raman spectroscopy. Density functional theoretical analysis reveals the bonding hierarchy in TlSe which involves ionic interaction in Tl+-Se while Tl3+-Se bonds are covalent, which causes significant lattice anharmonicity and intrinsic rattler-like low energy vibrations of Tl+, resulting in ultralow κL.

Terahertz Spectroscopic Probe of Hot Electron and Hole Transfer from Colloidal CsPbBr3 Perovskite Nanocrystals.

Colloidal all inorganic CsPbX3 (X = Cl, Br, I) nanocrystals (NCs) have emerged to be an excellent material for applications in light emission, photovoltaics, and photocatalysis. Efficient interfacial transfer of photogenerated electrons and holes are essential for a good photovoltaic and photocatalytic material. Using time-resolved terahertz spectroscopy, we have measured the kinetics of photogenerated electron and hole transfer processes in CsPbBr3 NCs in the presence of benzoquinone and phenothiazine molecules as electron and hole acceptors, respectively. Efficient hot electron/hole transfer with a sub-300 fs time scale is the major channel of carrier transfer thus overcomes the problem related to Auger recombination. A secondary transfer of thermalized carriers also takes place with time scales of 20-50 ps for electrons and 137-166 ps for holes. This work suggests that suitable interfaces of CsPbX3 NCs with electron and hole transport layers would harvest hot carriers, increasing the photovoltaic and photocatalytic efficiencies.

The H2 S Dimer is Hydrogen-Bonded: Direct Confirmation from Microwave Spectroscopy.

Ice and solid H2 S look as different as pears and oranges, leading Pauling to conclude that H2 O has hydrogen bonds and H2 S has van der Waals interactions. Now it is shown that the H2 S dimer, like the H2 O dimer, is indeed hydrogen-bonded.

Intrinsic Rattler-Induced Low Thermal Conductivity in Zintl Type TlInTe2.

Understanding the nature of chemical bonding and lattice dynamics together with their influence on phonon-transport is essential to explore and design crystalline solids with ultralow thermal conductivity for various applications including thermoelectrics. TlInTe2, with interlocked rigid and weakly bound substructures, exhibits lattice thermal conductivity as low as ca. 0.5 W/mK near room temperature, owing to rattling dynamics of weakly bound Tl cations. Large displacements of Tl cations along the c-axis, driven by electrostatic repulsion between localized electron clouds on Tl and Te ions, are akin to those of rattling guests in caged-systems. Heat capacity of TlInTe2 exhibits a broad peak at low-temperatures due to contribution from Tl-induced low-frequency Einstein modes as also evidenced from THz time domain spectroscopy. First-principles calculations reveal a strong coupling between large-amplitude coherent optic vibrations of Tl-rattlers along the c-axis, and acoustic phonons that likely causes the low lattice thermal conductivity in TlInTe2.

Terahertz Conductivity within Colloidal CsPbBr3 Perovskite Nanocrystals: Remarkably High Carrier Mobilities and Large Diffusion Lengths.

Colloidal CsPbBr3 perovskite nanocrystals (NCs) have emerged as an excellent light emitting material in last one year. Using time domain and time-resolved THz spectroscopy and density functional theory based calculations, we establish 3-fold free carrier recombination mechanism, namely, nonradiative Auger, bimolecular electron-hole recombination, and inefficient trap-assisted recombination in 11 nm sized colloidal CsPbBr3 NCs. Our results confirm a negligible influence of surface defects in trapping charge carriers, which in turn results into desirable intrinsic transport properties, from the perspective of device applications, such as remarkably high carrier mobility (∼4500 cm(2) V(-1) s(-1)), large diffusion length (>9.2 µm), and high luminescence quantum yield (80%). Despite being solution processed and possessing a large surface to volume ratio, this combination of high carrier mobility and diffusion length, along with nearly ideal photoluminescence quantum yield, is unique compared to any other colloidal quantum dot system.

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-ß receptor tyrosine kinase signaling.

The inhibitory reversible oxidation of protein tyrosine phosphatases (PTPs) is an important regulatory mechanism in growth factor signaling. Studies on PTP oxidation have focused on pathways that increase or decrease reactive oxygen species levels and thereby affect PTP oxidation. The processes involved in reactivation of oxidized PTPs remain largely unknown. Here the role of the thioredoxin (Trx) system in reactivation of oxidized PTPs was analyzed using a combination of in vitro and cell-based assays. Cells lacking the major Trx reductase TrxR1 (Txnrd1(-/-)) displayed increased oxidation of PTP1B, whereas SHP2 oxidation was unchanged. Furthermore, in vivo-oxidized PTP1B was reduced by exogenously added Trx system components, whereas SHP2 oxidation remained unchanged. Trx1 reduced oxidized PTP1B in vitro but failed to reactivate oxidized SHP2. Interestingly, the alternative TrxR1 substrate TRP14 also reactivated oxidized PTP1B, but not SHP2. Txnrd1-depleted cells displayed increased phosphorylation of PDGF-ß receptor, and an enhanced mitogenic response, after PDGF-BB stimulation. The TrxR inhibitor auranofin also increased PDGF-ß receptor phosphorylation. This effect was not observed in cells specifically lacking PTP1B. Together these results demonstrate that the Trx system, including both Trx1 and TRP14, impacts differentially on the oxidation of individual PTPs, with a preference of PTP1B over SHP2 activation. The studies demonstrate a previously unrecognized pathway for selective redox-regulated control of receptor tyrosine kinase signaling.

Activation of TADF in Photon Upconverting Crystals of Dinuclear Cu(I)-Iodide Complexes by Ligand Engineering.

This work reports that ligand engineering can modulate the triplet harvesting mechanism in iodide-bridged rhombic Cu2I2 complexes. Complex-1, with a smaller Cu-Cu distance, exhibits phosphorescence from 3(M+X)LCT and 3CC states with 66% quantum yield, whereas an increased Cu-Cu distance in complex-2 results in a switch of the emission from phosphorescence to TADF, which occurs via 1/3(M+X)LCT states with 83% quantum yield. The TADF property of complex-2 has been utilized for the fabrication of a pc-LED emitting efficient warm white light. Moreover, the high charge-transfer nature of these complexes leads to the emergence of third-harmonic generation (THG). Interestingly, complex-1 exhibits efficient third-harmonic generation with a χ(3) value of 1.15 × 10-18 m2 V-2 and LIDT value of 14.73 GW/cm2. This work aims to provide a structure-property relationship to achieve effective harvestation of triplet excitons in iodide-bridged rhombic Cu2I2 complexes and their effective utilization in OLED device fabrication and nonlinear photon upconversion processes.

Macroscopic Quantum Tunneling of a Topological Ferromagnet.

The recent advent of topological states of matter spawned many significant discoveries. The quantum anomalous Hall (QAH) effect is a prime example due to its potential for applications in quantum metrology, as well as its influence on fundamental research into the underlying topological and magnetic states and into axion electrodynamics. Here, electronic transport studies on a (V,Bi,Sb)2 Te3 ferromagnetic topological insulator nanostructure in the QAH regime are presented. This allows access to the dynamics of an individual ferromagnetic domain. The domain size is estimated to be in the 50-100 nm range. Telegraph noise resulting from the magnetization fluctuations of this domain is observed in the Hall signal. Careful analysis of the influence of temperature and external magnetic field on the domain switching statistics provides evidence for quantum tunneling (QT) of magnetization in a macrospin state. This ferromagnetic macrospin is not only the largest magnetic object in which QT is observed, but also the first observation of the effect in a topological state of matter.

Engineering TADF, mechanochromism, and second harmonic up-conversion properties in regioisomeric substitution space.

This research article explores the distinct TADF efficiency of three donor-acceptor based regio-isomers: DPAOCN (ortho-isomer), DPAMCN (meta-isomer), and DPAPCN (para-isomer). DPAPCN exhibits maximum TADF efficiency in both solution and solid-state with an impressive reverse inter-system crossing (RISC) rate of ∼106 s-1; the underlying cause being the minimum singlet-triplet splitting energy or ΔEST and maximum SOC (spin-orbit coupling) between the S1 & T1 states. Apart from TADF, differences in crystal packing of the regio-isomers result in intriguing bulk phase properties. DPAOCN, with its non-centrosymmetric P212121 space group and substantial crystal void volume, exhibits reversible tri-color mechanochromic luminescence behavior, while the meta and para isomers, due to their centrosymmetric packing and diminished crystal void volume, remain inert to mechanical pressure. Expanding the horizon of possibilities, the non-centrosymmetric nature of ortho-isomer further renders it an excellent SHG material, with a χ(2) value of 0.19 pm V-1 at 1220 nm and a laser-induced damage threshold (LIDT) value of 13.27 GW cm-2. Overall, a comprehensive investigation into the regio-isomers has been carried out, encompassing their TADF, SHG, and mechanochromic luminescent properties.

Mitochondrial thioredoxin reductase is essential for early postischemic myocardial protection.

BACKGROUND: Excessive formation of reactive oxygen species contributes to tissue injury and functional deterioration after myocardial ischemia/reperfusion. Especially, mitochondrial reactive oxygen species are capable of opening the mitochondrial permeability transition pore, a harmful event in cardiac ischemia/reperfusion. Thioredoxins are key players in the cardiac defense against oxidative stress. Mutations in the mitochondrial thioredoxin reductase (thioredoxin reductase-2, Txnrd2) gene have been recently identified to cause dilated cardiomyopathy in patients. Here, we investigated whether mitochondrial thioredoxin reductase is protective against myocardial ischemia/reperfusion injury. METHODS AND RESULTS: In mice, α-MHC-restricted Cre-mediated Txnrd2 deficiency, induced by tamoxifen (Txnrd2-/-ic), aggravated systolic dysfunction and cardiomyocyte cell death after ischemia (90 minutes) and reperfusion (24 hours). Txnrd2-/-ic was accompanied by a loss of mitochondrial integrity and function, which was resolved on pretreatment with the reactive oxygen species scavenger N-acetylcysteine and the mitochondrial permeability transition pore blocker cyclosporin A. Likewise, Txnrd2 deletion in embryonic endothelial precursor cells and embryonic stem cell-derived cardiomyocytes, as well as introduction of Txnrd2-shRNA into adult HL-1 cardiomyocytes, increased cell death on hypoxia and reoxygenation, unless N-acetylcysteine was coadministered. CONCLUSIONS: We report that Txnrd2 exerts a crucial function during postischemic reperfusion via thiol regeneration. The efficacy of cyclosporin A in cardiac Txnrd2 deficiency may indicate a role for Txnrd2 in reducing mitochondrial reactive oxygen species, thereby preventing opening of the mitochondrial permeability transition pore.