Tunable Toxicity of Bufadienolides is Regulated through a Configuration Inversion Catalyzed by a Short-Chain Dehydrogenase/Reductase.

Bufadienolides are toxic components widely found in amphibious toads that exhibit a wide range of biological activities. Guided by UPLC-QTOF-MS analysis, several 3-epi-bufadienolides with unique structures were isolated from the bile of the Asiatic toad, Bufo gargarizans. However, the enzymatic machinery of this epimerization in toads and its significance in chemical ecology remains poorly understood. Herein, we firstly compared the toxicities of two typical bufadienolides, bufalin (featuring a 14ß-hydroxyl) and resibufogenin (containing a 14, 15-epoxy group), with their corresponding 3-epi isomers in a zebrafish model. The results of the toxicology assays showed that the ratio of maximum non-toxic concentrations of these two pairs of compounds are 256 and 96 times, respectively, thereby indicating that 3-hydroxyl epimerization leads to a significant decrease in toxicity. Aiming to investigate the biotransformation of 3-epi bufadienolides in toads, we applied liver lysate to transform bufalin and found that it could stereoselectively catalyze the conversion of bufalin into its 3α-hydroxyl epimer. Following this, we cloned and characterized a short-chain dehydrogenase/reductase, HSE-1, from the toad liver cDNA library and verified its 3(ß→α)-hydroxysteroid epimerization activity. To the best of our knowledge, this is the first hydroxyl epimerase identified from amphibians that regulates the toxicity of animal-derived natural products.

Controllable high-performance memristors based on 2D Fe2GeTe3oxide for biological synapse imitation.

Memristors are an important component of the next-generation artificial neural network, high computing systems, etc. In the past, two-dimensional materials based memristors have achieved a high performance and low power consumption, though one at the cost of the other. Furthermore, their performance can not be modulated frequently once their structures are fixed, which remains the bottleneck in the development. Herein, a series of forming free memristors are fabricated with the same Cu/Fe3GeTe2oxide/Fe3GeTe2/Al structure, yet the On/Off ratio and set voltage is modulated continuously by varying the oxidation time during fabrication. With an optimal oxidation time, a large On/Off ratio (1.58 × 103) and low set voltage (0.74 V) is achieved in a single device. The formation and rapture of Al conductive filaments are found to be responsible for the memristors, and the filaments density and the cross-section area increase with the increase of current compliance, which achieves a higher On/Off ratio. The memristor can imitate basic biological synaptic functions using voltage pulses, demonstrating the potential for low-power consuming neuromorphic computing applications.

Bufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 µM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.

Flash healing of laser-induced graphene.

The advancement of laser-induced graphene (LIG) technology has streamlined the fabrications of flexible graphene devices. However, the ultrafast kinetics triggered by laser irradiation generates intrinsic amorphous characteristics, leading to high resistivity and compromised performance in electronic devices. Healing graphene defects in specific patterns is technologically challenging by conventional methods. Herein, we report the rapid rectification of LIG's topological defects by flash Joule heating in milliseconds (referred to as F-LIG), whilst preserving its overall structure and porosity. The F-LIG exhibits a decreased ID/IG ratio from 0.84 - 0.33 and increased crystalline domain from Raman analysis, coupled with a 5-fold surge in conductivity. Pair distribution function and atomic-resolution imaging delineate a broader-range order of F-LIG with a shorter C-C bond of 1.425 Å. The improved crystallinity and conductivity of F-LIG with excellent flexibility enables its utilization in high-performance soft electronics and low-voltage disinfections. Notably, our F-LIG/polydimethylsiloxane strain sensor exhibits a gauge factor of 129.3 within 10% strain, which outperforms pristine LIG by 800%, showcasing significant potential for human-machine interfaces.

Mushroom-like cobalt nickle metaphosphate@nickel diselenide core-shell nanorods for asymmetric supercapacitors.

Although transition metal metaphosphates (TMPOs) display special physical/chemical features and high theoretical capacities, their applications for supercapacitors (SCs) are still restricted by their low energy densities and inferior cycling stability. Herein, a novel strategy has been proposed to address these issues through in situ construction of cobalt nickle metaphosphate (Co0.2Ni0.8(PO3)2)@nickel diselenide (NiSe2) core-shell heterostructure on carbon paper (CP) as a self-supporting flexible electrode for SCs. Particularly, this unique mushroom-like porous nanoarchitecture assembled by one-dimensional (1D) Co0.2Ni0.8(PO3)2 nanorods and zero-dimensional (0D) NiSe2 nanospheres can expose abundant active sites and afford multi-dimensional channels, which favors rapid electron ions/electron transfer, accelerates the reaction kinetics, and alleviates volume changes during charging/discharging processes. Profiting from its well-aligned 1D/0D nanostructure and strong synergistic effect between Co0.2Ni0.8(PO3)2 and NiSe2, the Co0.2Ni0.8(PO3)2@NiSe2/CP electrode delivers a specific capacity of 219.4 mAh/g/0.414 mAh cm-2 at 1 A/g and good cycling stability with capacity retention of 90.7% after 5000 cycles, outperforming many previously reported TMPO-based electrodes in literature. Impressively, an asymmetric supercapacitor (ASC) device assembled with Co0.2Ni0.8(PO3)2@NiSe2 as cathode and porous carbon as anode achieves an energy density of 69.2 Wh kg-1 at 736.0 W kg-1 and maintains a capacity retention of 97.6% after 20,000 charge-discharge cycles. This work provides an efficient approach to design multi-dimensional hybrid nanomaterials for high-performance SCs.

Tunable asymmetric magnetoresistance in an Fe3GeTe2/graphite/Fe3GeTe2 lateral spin valve.

van der Waals (vdW) ferromagnetic heterojunctions, characterized by an ultraclean device interface and the absence of lattice matching, have emerged as indispensable and efficient building blocks for future spintronic devices. In this study, we present a seldom observed antisymmetric magnetoresistance (MR) behavior with three distinctive resistance states in a lateral van der Waals (vdW) structure comprising Fe3GeTe2 (FGT)/graphite/FGT. In contrast to traditional spin valves governed by the magnetization configurations of ferromagnetic electrodes (FEs), this distinct feature can be attributed to the interaction between FGT and the FGT/graphite interface, which is primarily influenced by the internal spin-momentum locking effect. Furthermore, modulation of the MR behavior is accomplished by employing the coupling between antiferromagnetic and ferromagnetic materials to adjust the coercive fields of two FEs subsequent to the in situ growth of an FGT oxide layer on FGT. This study elucidates the device physics and mechanism of property modulation in lateral spin valves and holds the potential for advancing the development of gate-tunable spintronic devices and next-generation integrated circuits.

Research progress of diabetic retinopathy and gut microecology.

According to the prediction of the International Diabetes Federation, global diabetes mellitus (DM) patients will reach 783.2 million in 2045. The increasing incidence of DM has led to a global epidemic of diabetic retinopathy (DR). DR is a common microvascular complication of DM, which has a significant impact on the vision of working-age people and is one of the main causes of blindness worldwide. Substantial research has highlighted that microangiopathy and chronic low-grade inflammation are widespread in the retina of DR. Meanwhile, with the introduction of the gut-retina axis, it has also been found that DR is associated with gut microecological disorders. The disordered structure of the GM and the destruction of the gut barrier result in the release of abnormal GM flora metabolites into the blood circulation. In addition, this process induced alterations in the expression of various cytokines and proteins, which further modulate the inflammatory microenvironment, vascular damage, oxidative stress, and immune levels within the retina. Such alterations led to the development of DR. In this review, we discuss the corresponding alterations in the structure of the GM flora and its metabolites in DR, with a more detailed focus on the mechanism of gut microecology in DR. Finally, we summarize the potential therapeutic approaches of DM/DR, mainly regulating the disturbed gut microecology to restore the homeostatic level, to provide a new perspective on the prevention, monitoring, and treatment of DR.

Proximity Effect-Induced Magnetoresistance Enhancement in a Fe3GeTe2/NbSe2/Fe3GeTe2 Magnetic Tunnel Junction.

The coupling between van der Waals-layered magnetic and superconducting materials holds the possibility of revealing novel physical mechanisms and realizing spintronic devices with new functionalities. Here, we report on the realization and investigation of a maximum ∼17-fold magnetoresistance (MR) enhancement based on a vertical magnetic tunnel junction of Fe3GeTe2 (FGT)/NbSe2/FGT near the NbSe2 layer's superconducting critical temperature (TC) of 6.8 K. This enhancement is attributed to the band splitting in the atomically thin NbSe2 spacer layer induced by the magnetic proximity effect on the material interfaces. However, the band splitting is strongly suppressed by the interlayer coupling in the thick NbSe2 layer. Correspondingly, the device with a thick NbSe2 layer displays no MR increase near TC but a current dependent on transport properties at extremely low temperatures. This work carefully investigates the mechanism of MR enhancement, paving an efficient way for the modulation of spintronics' properties and the achievement of spin-based integrated circuits.

Magnetoresistance studies of two-dimensional Fe3GeTe2nano-flake.

The magneto-transport properties of two-dimensional (2D) Fe3GeTe2(FGT) nano-flakes are carefully investigated with the variation of the temperature and the direction of the applied magnetic field (B). Four magnetoresistance (MR) behavior are obtained at different temperatures withBparalleling the flake's surface, because of the competition between the merging of different domains, spin fluctuation, and the spin momentum flipping. Different from the reported negative MR of bulk FGT, 2D FGT shows a positive MR behavior with the increase ofBat a low temperature in a lowBrange, owning to the domination of the spin momentum flipping induced by the weakening of the coupling between different layers with the decrease of the thickness of the FGT flake. The angle-dependence of the FGT MR is also investigated and can be well explained by the competition mentioned above.

Phylogenetic Analysis and Pathogenicity Assessment of Two Strains of Avian Influenza Virus Subtype H9N2 Isolated from Migratory Birds: High Homology of Internal Genes with Human H10N8 Virus.

Two human-infecting avian influenza viruses (AIVs), H7N9 and H10N8, have emerged in China, which further indicate that the H9N2 subtype of AIVs, as an internal gene donor, may have an important role in the generation of new viruses with cross-species transmissibility and pathogenicity. H9N2 viruses that contain such internal genes widely exist in poultry but are rarely reported in migratory birds. In this study, two strains of the H9N2 virus were isolated from fecal samples of migratory birds in 2014: one strain from Caizi Lake in Anhui Province and one from Chen Lake in Hubei Province of China. Nucleotide sequence analysis revealed high homology of all six internal genes of these two strains with the internal genes of the human H10N8 virus in Jiangxi Province, as well as with the human H7N9 virus. Phylogenetic analysis indicated a possible origin of these two strains from poultry in South China. Both of the two viruses tested could replicated in respiratory organs of infective mice without adaption, by both strains of the H9N2 AIVs from wild birds, suggesting their potential capacity for directly infecting mammals. Our findings indicate the existence of H9N2 viruses that contain internal genes highly homologous with human H10N8 or H7N9 viruses. Wild birds can contribute to the spread of the H9N2 virus that contains the "harmful" internal gene complex, leading to gene rearrangement with other influenza viruses and to the generation of new pathogenic viruses. Therefore, strengthening AIV surveillance in wild birds can promote an understanding of the presence and prevalence of viruses and provide scientific evidence for the prevention and control of AIVs and human-infecting AIVs.

Clinical observation of different surgical methods for metaphyseal sequelae of ulna / 中国骨伤

OBJECTIVE@#To investigate the effect and safety of ulnar osteochondroma resection, ulnar minimally invasive osteotomy, external fixation and ulnar lengthening in the treatment of forearm deformity of metaphyseal extension of ulna.@*METHODS@#From August 2005 to December 2013, there were 20 cases of ulnar metaphyseal sequelae, including 15 males and 5 females, aged from 7 to 13(10.00±2.34) years, the course of disease ranged for 6 to 11(8.10±1.52) months. The clinical manifestations were shortening of the affected forearm and bending to the ulnar side. The postoperative evaluation included pain, activities of daily living, orthopedic effect and the range of motion of wrist, elbow and forearm. The radiological evaluation included ulnar length, radial joint inclination angle and wrist epiphysis growth.@*RESULTS@#All patients healed without infection. The only operation related to complications was ulnar lengthening, including 1 case of nonunion, 2 cases of ulnar lengthening callus fracture and 1 case of temporary radial nerve palsy. All patients were followed up for 4 to 7.5 years, with an average of (6.03±1.33) years. There were statistically significant differences in changes of wrist radial deviation, ulnar deviation, forearm pronation and supination in all cases (@*CONCLUSION@#Ulnar lengthening is not beneficial to prevent the development of long-term deformity. Simple resection of osteochondroma of distal ulna is beneficial to prevent the development of deformity. Patients with limited rotation of wrist joint and forearm and strong demand for improvement of appearance can be actively treated.

Development of Chinese forensic Y-STR DNA database / 法医学杂志

Y chromosome is a male-specific paternal inherited chromosome. The STR markers on Y chromosome have been widely used in forensic practices. This article summarizes the characteristics of Y-STR and some factors are considered of selecting appropriate Y-STR markers for Chinese population. The prospects of existing and potential forensic applications of Y-STR profiles are discussed including familial excluding, familial searching, crowd source deducing, mixture sample testing, and kinship identifying. The research, development, verification of Y-STR kit, Y-STR mutation rate, and search software are explored and some suggestions are given.