Human TRMT1 catalyzes m2G or m22G formation on tRNAs in a substrate-dependent manner.

TRMT1 is an N2-methylguanosine (m2G) and N2,N2-methylguanosine (m22G) methyltransferase that targets G26 of both cytoplasmic and mitochondrial tRNAs. In higher eukaryotes, most cytoplasmic tRNAs with G26 carry m22G26, although the majority of mitochondrial G26-containing tRNAs carry m2G26 or G26, suggesting differences in the mechanisms by which TRMT1 catalyzes modification of these tRNAs. Loss-of-function mutations of human TRMT1 result in neurological disorders and completely abrogate tRNA:m22G26 formation. However, the mechanism underlying the independent catalytic activity of human TRMT1 and identity of its specific substrate remain elusive, hindering a comprehensive understanding of the pathogenesis of neurological disorders caused by TRMT1 mutations. Here, we showed that human TRMT1 independently catalyzes formation of the tRNA:m2G26 or m22G26 modification in a substrate-dependent manner, which explains the distinct distribution of m2G26 and m22G26 on cytoplasmic and mitochondrial tRNAs. For human TRMT1-mediated tRNA:m22G26 formation, the semi-conserved C11:G24 serves as the determinant, and the U10:A25 or G10:C25 base pair is also required, while the size of the variable loop has no effect. We defined the requirements of this recognition mechanism as the "m22G26 criteria". We found that the m22G26 modification occurred in almost all the higher eukaryotic tRNAs conforming to these criteria, suggesting the "m22G26 criteria" are applicable to other higher eukaryotic tRNAs.

Recognizing the Importance of Fast Nonisothermal Crystallization for High-Performance Two-Dimensional Dion-Jacobson Perovskite Solar Cells with High Fill Factors: A Comprehensive Mechanistic Study.

Two-dimensional (2D) Dion-Jacobson (DJ) perovskite solar cells (PSCs), despite their advantage in versatility of n-layer variation, are subject to poor photovoltaic efficiency, particularly in the fill factor (FF), compared to their three-dimensional counterparts. To enhance the performance of DJ PSCs, the process of growing crystals and hence the corresponding morphology of DJ perovskites are of prime importance. Herein, we report the fast nonisothermal (NIT) crystallization protocol that is previously unrecognized for 2D perovskites to significantly improve the morphology, orientation, and charge transport of the DJ perovskite films. Comprehensive mechanistic studies reveal that the NIT effect leads to the secondary crystallization stage, forming network-like channels that play a vital role in the FF's leap-forward improvement and hence the DJ PSC's performance. As a whole, the NIT crystallized PSCs demonstrate a high power conversion efficiency and an FF of up to 19.87 and 86.16%, respectively. This research thus provides new perspectives to achieve highly efficient DJ PSCs.

Freeze-thaw-stable high internal phase emulsions stabilized by soy protein isolate and chitosan complexes at pH 3.0 as promising mayonnaise replacers.

The development of cholesterol-free mayonnaise has attracted increasing interest in the food colloid field, due to the potential health concerns as a result of consumption of cholesterol-rich mayonnaise. One effective strategy in this regard is to substitute or partially substitute egg yolk with other organic emulsifiers and stabilizers, without affecting the quality of the product. In the work, we reported an effective strategy to fabricate high freeze-thaw-stability high internal phase emulsions (HIPEs), using complexes of a heated soy protein isolate (SPI) and chitosan (CS) at pH 3.0 as the emulsifiers and stabilizers. The SPI/CS complexes, formed even at a very low CS-to-SPI ratio, e.g., 1:10, showed a high capacity to stabilize HIPEs with a high freeze-thaw stability. Increasing the CS-to-SPI ratio in the complexes resulted in a progressive strengthening of gel network in the corresponding HIPEs, together with a gradual improvement of emulsification performance. The gel network of the HIPEs stabilized by the SPI/CS complexes was mainly maintained by the inter-droplet noncovalent interactions involving the CS molecules. The presence of CS also progressively increased the percentage of adsorbed proteins at the interface, and decreased the surface coverage of proteins at the interface. The high freeze-thaw stability of such HIPEs might be unrelated to the ice crystal formation during the freezing, and was more likely associated with the strong steric repulsion contributed to the adsorbed CS molecules between different droplets. The results indicated that the complexation of heated SPI and CS could provide an effective strategy to facilely fabricate outstanding freeze-thaw-stability HI PEs as potential mayonnaise replacers.

A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.

Position 34 of tRNA is a discriminative element for m5C38 modification by human DNMT2.

Dnmt2, a member of the DNA methyltransferase superfamily, catalyzes the formation of 5-methylcytosine at position 38 in the anticodon loop of tRNAs. Dnmt2 regulates many cellular biological processes, especially the production of tRNA-derived fragments and intergenerational transmission of paternal metabolic disorders to offspring. Moreover, Dnmt2 is closely related to human cancers. The tRNA substrates of mammalian Dnmt2s are mainly detected using bisulfite sequencing; however, we lack supporting biochemical data concerning their substrate specificity or recognition mechanism. Here, we deciphered the tRNA substrates of human DNMT2 (hDNMT2) as tRNAAsp(GUC), tRNAGly(GCC) and tRNAVal(AAC). Intriguingly, for tRNAAsp(GUC) and tRNAGly(GCC), G34 is the discriminator element; whereas for tRNAVal(AAC), the inosine modification at position 34 (I34), which is formed by the ADAT2/3 complex, is the prerequisite for hDNMT2 recognition. We showed that the C32U33(G/I)34N35 (C/U)36A37C38 motif in the anticodon loop, U11:A24 in the D stem, and the correct size of the variable loop are required for Dnmt2 recognition of substrate tRNAs. Furthermore, mammalian Dnmt2s possess a conserved tRNA recognition mechanism.

The Observation of Interchain Motion in Self-Assembled Crystalline Platinum(II) Complexes: An Exquisite Case but By No Means the Only One in Molecular Solids.

In organic and organometallic solids, upon electronic excitation, most intermolecular structural relaxations follow a pathway along the π-π stacking direction or metal-metal bond with significant coupling strength. Differently, we discovered that the self-assembled platinum(II) complexes, Pt(fppz)2, exhibit an unusual interchain contraction. The ground-state and excited-state multiple local minima were distinguished by temperature-dependent excitation/emission spectra, indicating the existence of multiple local minima. The time-resolved emission decay revealed the excited-state structural relaxation lifetime with τobs = 41 ns at 298 K. Temperature-dependent X-ray diffraction analysis showed that the packing geometries contract 0.6 Å along the interchain direction (a-axis) at 50 K compared to the geometries at 298 K. Such structural displacements render the slow internal conversion rate in the excited states. We thus demonstrate the correlation between the packing geometries and the excited-state dynamics of the self-assembled Pt(II) complexes, shedding light on the unique direction of interchain structural deformation of the molecular aggregates.

[2,2](5,8)Picenophanedienes: Syntheses, Structural Analyses, Molecular Dynamics, and Reversible Intramolecular Structure Conversion.

This study presents an important and efficient synthetic approach to 5,8-dibromo-2,11-di-tert-butylpicene (3), with multigram scale, which was then converted to a new series of picenophanes (6-10). The tub-shaped [2,2](5,8)picenophanediene 8 with two cis-ethylene linkers was explored using X-ray crystallography. The tub-to-tub inversion proceed through the successive bending of the linkers and the barrier for isopropyl-substituted derivative 10 was experimentally estimated to be 18.7 kcal/mol. Picenophanes with a large π-system and semi-rigid structure exhibited anomalous photophysical properties. The ethano-bridged picenophane shows the weak exciton delocalization while the cis-ethylene-bridged picenophane exhibits dual emission rendered by the weakly delocalized exciton and excimer. With the aid of the ultrafast time-resolved emission spectroscopy, the mechanism of the excimer formation is resolved, showing a unique behavior of two-state reversible reaction with fast structural deformation whose lifetime is around 20 ps at 298 K. This work demonstrates that the slight difference in the bridge of tub-shaped picenophanes renders distinct photophysical behavior, revealing the potential of harnessing inter-moiety reaction in the picenophane systems.

Highly Emissive Dinuclear Platinum(III) Complexes.

Dinuclear Pt(III) complexes were commonly reported to have short-lived lowest-lying triplet states, resulting in extremely weak or no photoluminescence. To overcome this obstacle, a new series of dinuclear Pt(III) complexes, named Pt2a-Pt2c, were strategically designed and synthesized using donor (D)-acceptor (A)-type oxadiazole-thiol chelates as bridging ligands. These dinuclear Pt(III) complexes possess a d7-d7 electronic configuration and exhibit intense phosphorescence under ambient conditions. Among them, Pt2a exhibits orange phosphorescence maximized at 618 nm in degassed dichloromethane solution (Φp ≈ 8.2%, τp ≈ 0.10 µs) and near-infrared (NIR) emission at 749 nm (Φp ≈ 10.1% τp ≈ 0.66 µs) in the crystalline powder and at 704 nm (Φp ≈ 33.1%, τp ≈ 0.34 µs) in the spin-coated neat film. An emission blue-shifted by more than 3343 cm-1 is observed under mechanically ground crystalline Pt2a, affirming intermolecular interactions in the solid states. Time-dependent density functional theory (TD-DFT) discloses the lowest-lying electronic transition of Pt2a-Pt2c complexes to be a bridging ligand-metal-metal charge transfer (LMMCT) transition. The long-lived triplet states of these dinuclear platinum(III) complexes may find potential use in lighting. Employing Pt2a as an emitter, high-performance organic light-emitting diodes (OLEDs) were fabricated with NIR emission at 716 nm (η = 5.1%), red emission at 614 nm (η = 8.7%), and white-light emission (η = 11.6%) in nondoped, doped (in mCP), and hybrid (in CzACSF) devices, respectively.

Tuning Electron-Withdrawing Strength on Phenothiazine Derivatives: Achieving 100 % Photoluminescence Quantum Yield by NO2 Substitution.

The weak fluorescence (quantum yield <1 % in cyclohexane) of phenothiazine (PTZ) impedes its further application. In addition, the nitro group (NO2 ) is a well-known fluorescence quencher. Interestingly, we obtained a highly fluorescent chromophore by combining these two moieties, forming 3-nitrophenothiazine (PTZ-NO2 ). For comparison, a series of PTZ derivatives bearing electron-withdrawing groups (EWGs; CN and CHO) or electron-donating groups (EDGs; OMe) at the 3-position have been designed and synthesized. The phenothiazines bearing EWGs exhibited enhanced emission compared with the parent PTZ or EDG derivatives. Computational approaches unveiled that for PTZ and PTZ-OMe, the transitions are from HOMOs dominated by π orbitals to LUMOs of mixed sulfur nonbonding-π* orbitals, and hence are partially forbidden. In contrast, the EWGs lower the energy level of the lone-pair electrons on the sulfur atom, thereby suppressing the mixing of the nonbonding orbital with the π* orbital in the LUMO, such that the allowed ππ* transition becomes dominant. This work thus demonstrates a judicious chemical design to fine-tune the transition character in PTZ analogues, with PTZ-NO2 attaining 100 % emission quantum yields in nonpolar solvent.

Clinical Analysis of 1593 Patients with Infectious Endophthalmitis: A 12-Year Study at a Tertiary Referral Center in Western China.

BACKGROUND: Infectious endophthalmitis is a severe ocular inflammation which can cause devastating visual loss. The aim of the study was to identify the demographic and clinical features of infectious endophthalmitis in Western China for better prophylaxis and treatment of this disease. METHODS: A.retrospective, cross-sectional study was conducted based on the medical records of inpatients having infectious endophthalmitis in a tertiary referral center in Western China between 2005 and 2016. RESULTS: The common cause of infectious endophthalmitis was trauma (82.6%), endogenous (7.8%), ophthalmic surgery (6.9%), and corneal ulcer with perforation (2.7%). These four etiological groups differed in age, gender, enucleation rate, visual outcome, etc. The number of cases in the first 6 years accounted for 38.7% of the total collection, which in the second 6 years accounted for 61.3%. The etiology patterns were different between these two periods. Altogether 51.3% of patients received pars plana vitrectomy, 13.9% of patients underwent evisceration, and the remaining 34.8% received other treatments. Of the 670 cases that had culture results, 266 (39.7%) were culture positive and 177 (66.5%) were Gram-positive organisms, 64 (24.1%) were Gram-negative organisms, 11 (4.1%) had fungal infection, and 14 (5.3%) were infected by multiple pathogens. CONCLUSIONS: There was an upward trend of the occurrence of infectious endophthalmitis in Western China for the past decade. The demographic and clinical characteristics of infectious endophthalmitis in Western China had its own characteristics and differed from those of developed countries. Here, open globe trauma was the most common cause of endophthalmitis, most traumatic endophthalmitis patients were male, and most of the injuries were work related, implicate that we should strengthen the education and application of ocular safety regulation specifically targeting the workplace.

[Purtscher-like retinopathy associated with antibiotic anaphylaxis].

OBJECTIVE: We report a case of an 18-year-old woman with systemic antibiotic anaphylaxis who presented anasarca and bilateral visual loss two weeks after the intravenous use of pazufloxacin. Ancillary fundus tests revealed bilateral cotton-wool spots, Purtscher flecken, edema, and retinal arteriolar occlusion around the optic disc. After pulse corticosteroid, administration of anti-anaphylactic agent, and general support therapy for one month, the patient showed a favorable change, with the symptoms lessened or free systemically, except the continuous aggravation of fundus ischemic change. After two intravitreal injections of Ranibizumab, there were still a large area of capillary non-perfusion and neovacularizations in the binocular retina, resulting in vitreous hemorrhage. The patient's visual acuity had still light perception after right-eye vitrectomy and presented no improvement during the postoperative follow-up of two years. Literature review revealed that there were many causes associated with Purtscher-like retinopathy, and the consequent visual impairment varied significantly. Prompt management of the underlying condition is crucial in giving the patient the best chance to restore vision.

Single-Drop Raman Imaging Exposes the Trace Contaminants in Milk.

Better milk safety control can offer important means to promote public health. However, few technologies can detect different types of contaminants in milk simultaneously. In this regard, the present work proposes a single-drop Raman imaging (SDRI) strategy for semiquantitation of multiple hazardous factors in milk solutions. By developing SDRI strategy that incorporates the coffee-ring effect (a natural phenomenon often presents in a condensed circle pattern after a drop evaporated) for sample pretreatment and discrete wavelet transform for spectra processing, the method serves well to expose typical hazardous molecular species in milk products, such as melamine, sodium thiocyanate and lincomycin hydrochloride, with little sample preparation. The detection sensitivity for melamine, sodium thiocyanate, and lincomycin hydrochloride are 0.1 mg kg-1, 1 mg kg-1, and 0.1 mg kg-1, respectively. Theoretically, we establish that the SDRI represents a novel and environment-friendly method that screens the milk safety efficiently, which could be well extended to inspection of other food safety.

[Protective effects of polysacchride of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan induced diabetic rats].

OBJECTIVE: To study the protective effects of polysaccharide of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan (ALX) induced diabetic rats. METHOD: With the doses of polysaccharide of Spirulina platensis (PSP) and Sargassum thunbeergii (PST) compound (1:1) 12.261, 36.783, 110.349 mg x kg(-1) by i.g. administration to alloxan induced diabetic rats respectively for 6 weeks. Then the blood glucose and the TC, HDL-C, TG, NO, ET in serum were detected. The contraction and relaxation response to NE and ACh in aortic rings of the alloxan induced diabetic rats has been studied. RESULT: The results showed the compound of PSP and PST could decrease the blood glucose and the TC, TG, NO, ET in serum and increase HDL-C than in the alloxan induced diabetic rats. The contraction responses to NE in aortic rings of the alloxan induced diabetic rats were significantly elevated in the normal rats, and the responses to ACh were significantly lower. PSP and PST compound could significantly lower the responses to NE and significantly elevate the responses to ACh in aortic rings of the alloxan induced diabetic rats. CONCLUSION: PSP and PST compound could decrease blood glucose and could protect the vascular of alloxan induced diabetic rats.