Hundred-Fold Enhancement in the Anomalous Hall Effect Induced by Hydrogenation.

The anomalous Hall effect (AHE) is one of the most fascinating transport properties in condensed matter physics. However, the AHE magnitude, which mainly depends on net spin polarization and band topology, is generally small in oxides and thus limits potential applications. Here, we demonstrate a giant enhancement of AHE in a LaCoO3-induced 5d itinerant ferromagnet SrIrO3 by hydrogenation. The anomalous Hall resistivity and anomalous Hall angle, which are two of the most critical parameters in AHE-based devices, are found to increase to 62.2 µΩ·cm and 3%, respectively, showing an unprecedentedly large enhancement ratio of ∼10000%. Theoretical analysis suggests the key roles of Berry curvature in enhancing AHE. Furthermore, the hydrogenation concomitantly induces the significant elevation of Curie temperature from 75 to 160 K and 40-fold reinforcement of coercivity. Such giant regulation and very large AHE magnitude observed in SrIrO3 could pave the path for 5d oxide devices.

Climate has contributed to population diversification of Daphnia galeata across Eurasia.

Climate is a fundamental abiotic factor that plays a key role in driving the evolution, distribution and population diversification of species. However, there have been few investigations of genomic signatures of adaptation to local climatic conditions in cladocerans. Here, we have provided the first high-quality chromosome-level genome assembly (~143 Mb, scaffold N50 12.6 Mb) of the waterflea, Daphnia galeata, and investigated genomic variation in 22 populations from Central Europe and Eastern China. Our ecological-niche models suggested that the historic distribution of D. galeata in Eurasia was significantly affected by Quaternary climate fluctuations. We detected pronounced genomic and morphometric divergences between European and Chinese D. galeata populations. Such divergences could be partly explained by genomic signatures of thermal adaptation to distinct climate regimes: a set of candidate single-nucleotide polymorphisms (SNPs) potentially associated with climate were detected. These SNPs were in genes significantly enriched in the Gene ontology terms "determination of adult lifespan" and "translation repressor activity", and especially, mthl5 and SOD1 involved in the IIS pathway, and EIF4EBP2 involved in the target of the rapamycin signalling pathway. Our study indicates that certain alleles might be associated with particular temperature regimes, playing a functional role in shaping the population structure of D. galeata at a large geographical scale. These results highlight the potential role of molecular variation in the response to climate variation, in the context of global climate change.

Phylogeography and genetic diversity of the Scapholeberis kingii species complex (Cladocera: Daphniidae) in China.

There is increasing interest in the diversity and phylogeography of aquatic invertebrate zooplankton in the Eastern Palearctic, yet this topic remains largely unexplored in China. Here, we investigated the lineage diversity and phylogeography of an important cladoceran taxon, the Scapholeberis kingii (Cladocera: Daphniidae) species complex, members of which live in the surface layers of freshwater ecosystems. We identified only the S. smirnovi morphospecies from this species complex in 29 of 491 Chinese water bodies examined. Its phylogenetic position was verified using both a mitochondrial (mitochondrial cytochrome c oxidase subunit I; COI) and a nuclear marker (the nuclear large subunit ribosomal RNA gene; 28S). Pronounced geographical separation among three S. smirnovi mitochondrial lineages was observed in China: only a single lineage (Lineage A) was present in the Eastern Plain, whereas Lineages B and C were restricted to the Inner Mongolia-Xinjiang Plateau and the Qinghai-Tibetan Plateau respectively. This deep mtDNA divergence and the substantial genetic differentiation among S. smirnovi populations from different regions is likely a result of the rapid uplift of the Qinghai-Tibetan Plateau and associated ecological changes. This study contributes to an understanding of the genetic diversity of the S. kingii complex, a key component of neustonic zooplankton.

Diversity of Brachionus plicatilis species complex (Rotifera) in inland saline waters from China: Presence of a new mitochondrial clade on the Tibetan Plateau.

The biogeography and molecular phylogeny of invertebrate zooplankton populations from inland saline waters remains under-explored in the Eastern Palearctic, especially the Qinghai-Tibetan Plateau. Here, we surveyed the diversity of the Brachionus plicatilis Müller, 1786 species complex from inland saline waters across China. We compared morphometrics with DNA taxonomy (using two genetic markers: the mitochondrial cytochrome c oxidase subunit I (COI) gene and the nuclear internal transcribed spacer (ITS-1)). Our phylogenies based on the sequences of ITS-1 recognized two distinct clades (i.e. two species: B. plicatilis sensu stricto (s.s.) and B. asplanchnoidis) in China. We detected two mitochondrial clades within B. plicatilis s.s and one within B. asplanchnoidis across China, consistent with the three morphogroups present. One of these three clades was novel and restricted to the Qinghai-Tibetan Plateau, where it exhibited evidence of recent expansion across the region. The new mitochondrial clade fell within B. plicatilis s.s. but was sister to all other mitochondrial sequences of that species, suggesting a period of isolation from other populations. Moreover, significant morphological differences were identified: B. plicatilis s.s. from the Qinghai-Tibetan Plateau had a larger lorica length and width than did members of this species from lowland China. Our data demonstrate the successful adaptation of this species complex to the harsh environment of the Qinghai-Tibetan Plateau.

Ceriodaphnia (Cladocera: Daphniidae) in China: Lineage diversity, phylogeography and possible interspecific hybridization.

The distribution and species/lineage diversity of freshwater invertebrate zooplankton remains understudied in China. Here, we explored the species/lineage diversity and phylogeography of Ceriodaphnia species across China. The taxonomy of this genus is under-explored. Seven morphospecies of Ceriodaphnia (C. cornuta, C. laticaudata, C. megops, C. pulchella, C. quadrangula, C. rotunda and C. spinata) were identified across 45 of 422 water bodies examined. Rather little morphological variation was observed within any single morphospecies regardless of country of origin. Nevertheless, we recognized that some or all of these morphospecies might represent species complexes. To investigate this, phylogenetic relationships within and among these morphospecies were investigated based on mitochondrial (partial cytochrome c oxidase subunit I gene) and nuclear (partial 28S rRNA gene) markers. The mitochondrial marker placed these populations in nine lineages corresponding to the morphospecies: C. laticaudata and C. pulchella were each represented by two lineages, suggesting that both are species complexes. The remaining five morphospecies were each represented by a single mtDNA lineage. Three of the nine mitochondrial lineages (belonging to C. pulchella, C. rotunda and C. megops) are newly reported and exhibited a restricted distribution within China. The nuclear-DNA phylogeny also recognized seven Ceriodaphnia taxa within China. We detected occasional mito-nuclear discordances in Ceriodaphnia taxa across China, suggesting interspecific introgression and hybridization. Our study contributes to an understanding of the species/lineage diversity of Ceriodaphnia, a genus with understudied taxonomy.

Lipid-specific interactions determine the organization and dynamics of membrane-active peptide melittin.

The cell membranes of different cells deviate significantly in lipid compositions and thus provide varying biological environments to modulate the diffusion, organization and the resultant function of biomacromolecules. However, the detailed modulation mechanism remains elusive especially in consideration of the current overuse of the simplified membrane models such as the pure phosphatidylcholine (PC) membrane. In this work, with the typical membrane-active peptide melittin, we demonstrated that a more complicated membrane environment, such as the bacterial (IME) or plasma membrane (PM), would significantly change the organization and dynamics of melittin, by using molecular dynamics simulations as a "computational microscope". It was found that in these membrane systems, adding melittin would cause a varying degree of reduction in the lateral diffusion of lipids due to the different assembly states of peptides. Melittin tended to aggregate to oligomers in the pure PC membrane, mostly as a tetramer or trimer, while in IME or PM, its degree of oligomerization was significantly reduced. More surprisingly, melittin displayed a strong affinity with ganglioside GM3 in PM, leading to the formation of melittin-GM3 nanoclusters, which hindered its diffusion and further oligomerization. Additionally, small changes in the residue sequence of melittin could modulate the degree or structure of the peptide oligomer. Our work provides a typical example of a study on the organization and dynamics of pore-forming peptides in specific membrane environments and has great significance on the optimization of peptide sequences and the design of helix bundles in the membrane for target biological function.

A phosphine-mediated domino sequence of salicylaldehyde with but-3-yn-2-one: rapid access to chromanone.

Chromanone is a privileged structure with a wide range of unique biological activities. A phosphine-promoted, three-component domino sequence of salicylaldehyde with but-3-yn-2-one was well designed for the construction of the chromanone skeleton under mild conditions. As a consequence, a series of novel chromanone analogues bearing an all-carbon quaternary center were facilely assembled from commercially available starting materials with moderate to good yields, which hold promising applications in pharmacological studies. Mechanistic experiments were conducted to confirm the proposed mechanism.

Visible-Light-Driven, Photoredox-Catalyzed Cascade of ortho-Hydroxycinnamic Esters To Access 3-Fluoroalkylated Coumarins.

A general and straightforward protocol for di-/perfluoroalkylation of ortho-hydroxycinnamic esters via a photoredox-catalyzed cascade was developed to access a variety of 3-fluoroalkylated coumarins. This method was characterized by all-in-one synthetic design, simplified operation, mild reaction conditions, and broad substrate scope. Moreover, a sequential one-pot procedure starting from commercially available salicylaldehyde was also successfully realized to synthesize 3-fluoroalkylated coumarins.

Construction of Bispirooxindole Heterocycles via Palladium-Catalyzed Ring-Opening Formal [3 + 2]-Cycloaddition of Spirovinylcyclopropyl Oxindole and 3-Oxindole Derivatives.

A palladium-catalyzed ring-opening oxo-formal [3 + 2]-cycloaddition reaction of novel donor-acceptor spirovinylcyclopropyl oxindole with 3-oxindole is described. The developed protocol provides facile access to oxo-bispirooxindole derivatives in good yields (up to 82% yield) with excellent diastereoselectivities (up to 20:1 dr).

Intramolecular hydrogen-bonding-assisted phosphine-catalysed [3 + 2] cyclisation of ynones with o-hydroxy/amino benzaldehydes.

A new strategy for the synthesis of functionalized tetrahydrofuran derivatives was developed via a phosphine-catalysed [3 + 2] cyclization reaction of aromatic aldehydes with 4-phenylbut-3-yn-2-one. This is the first example of intermolecular cyclization of ynones with benzaldehydes, which essentially benefited from the intramolecular hydrogen bonding. This new protocol features a broad substrate scope, mild reaction conditions, operational simplicity and easy scale-up.

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane.

Antimicrobial peptides (AMPs), as a key component of the immune defense systems of organisms, are a promising solution to the serious threat of drug-resistant bacteria to public health. As one of the most representative and extensively studied AMPs, melittin has exceptional broad-spectrum activities against microorganisms, including both Gram-positive and Gram-negative bacteria. Unfortunately, the action mechanism of melittin with bacterial membranes, especially the underlying physics of peptide-induced membrane poration behaviors, is still poorly understood, which hampers efforts to develop melittin-based drugs or agents for clinical applications. In this mini-review, we focus on recent advances with respect to the membrane insertion behavior of melittin mostly from a computational aspect. Membrane insertion is a prerequisite and key step for forming transmembrane pores and bacterial killing by melittin, whose occurrence is based on overcoming a high free-energy barrier during the transition of melittin molecules from a membrane surface-binding state to a transmembrane-inserting state. Here, intriguing simulation results on such transition are highlighted from both kinetic and thermodynamic aspects. The conformational changes and inter-peptide cooperation of melittin molecules, as well as melittin-induced disturbances to membrane structure, such as deformation and lipid extraction, are regarded as key factors influencing the insertion of peptides into membranes. The associated intermediate states in peptide conformations, lipid arrangements, membrane structure, and mechanical properties during this process are specifically discussed. Finally, potential strategies for enhancing the poration ability and improving the antimicrobial performance of AMPs are included as well.

Membrane-Active Peptides Attack Cell Membranes in a Lipid-Regulated Curvature-Generating Mode.

Membrane-active peptides (MAPs) exhibit great potential in biomedical applications due to their unique ability to overcome the cell membrane barrier. However, the interactions between MAPs and membranes are complex, and little is known about the possibility of MAP action being specific to certain types of membranes. In this study, a combination of molecular dynamics simulations and theoretical analysis was utilized to investigate the interactions between typical MAPs and realistic cell membrane systems. Remarkably, the simulations revealed that MAPs can attack membranes by generating and sensing positive mean curvature, which is dependent on lipid composition. Furthermore, theoretical calculations demonstrated that this lipid-regulated curvature-based membrane attack mechanism is an integrated result of multiple effects, including peptide-induced membrane wedge and softening effects, the lipid shape effect, the area-difference elastic effect, and the boundary edge effect of formed peptide-lipid nanodomains. This study enhances our comprehension of MAP-membrane interactions and highlights the potential for developing membrane-specific MAP-based agents.

Chromosome-scale genome assembly of the freshwater cladoceran crustacean Chydorus sphaericus: A resource for discovery of genes responsive to ecological challenges.

The genus Chydorus Leach 1816 (family Chydoridae) is a diverse and ecologically important taxon within freshwater ecosystems. Despite having been widely used in ecological, evolutionary and eco-toxicological studies, no high-quality genomic resource is available for any member of the genus. Here, we present a high-quality chromosome-level assembly of the C. sphaericus genome by combining 7.40 Gb (∼ 50 × coverage) PacBio reads, 19.28 Gb (∼ 135 × coverage) Illumina paired-end reads, and 34.04 Gb Hi-C reads. Our genome assembly is approximately 151 Mb, with contig and scaffold N50 lengths of 1.09 Mb and 13.70 Mb, respectively. The assembly captured 94.9% of the complete eukaryotic BUSCO. Repetitive elements accounted for 17.6% of the genome, and 13,549 protein-coding genes were predicted (based on transcriptome sequencing data, ab-initio or homology-based prediction), of which 96.4% have been functionally annotated in the NCBI-NR database. We identified 303 gene families specific to C. sphaericus, mainly families enriched in functions related to immune response, visual senses and detoxification. Interestingly, we also found 53 significantly expanded gene families in C. sphaericus, mostly with functions related to detoxification. This high-quality assembly genome will act as a reference genome for C. sphaericus and benefit studies on functional and comparative genomics of Chydorus and other crustaceans.

A broad-spectrum gas sensor based on correlated two-dimensional electron gas.

Designing a broad-spectrum gas sensor capable of identifying gas components in complex environments, such as mixed atmospheres or extreme temperatures, is a significant concern for various technologies, including energy, geological science, and planetary exploration. The main challenge lies in finding materials that exhibit high chemical stability and wide working temperature range. Materials that amplify signals through non-chemical methods could open up new sensing avenues. Here, we present the discovery of a broad-spectrum gas sensor utilizing correlated two-dimensional electron gas at a delta-doped LaAlO3/SrTiO3 interface with LaFeO3. Our study reveals that a back-gating on this two-dimensional electron gas can induce a non-volatile metal to insulator transition, which consequently can activate the two-dimensional electron gas to sensitively and quantitatively probe very broad gas species, no matter whether they are polar, non-polar, or inert gases. Different gas species cause resistance change at their sublimation or boiling temperature and a well-defined phase transition angle can quantitatively determine their partial pressures. Such unique correlated two-dimensional electron gas sensor is not affected by gas mixtures and maintains a wide operating temperature range. Furthermore, its readout is a simple measurement of electric resistance change, thus providing a very low-cost and high-efficient broad-spectrum sensing technique.

Interactions between polymyxin B and various bacterial membrane mimics: A molecular dynamics study.

Polymyxin B (PMB) is clinically used as a last-line therapy against life-threatening Gram-negative "superbugs". However, thorough understanding of the membrane actions of PMB at a molecular level is still lacking. In this work, a variety of bacterial membrane mimics with varying lipid compositions were built, and their interactions with PMB were systematically investigated using coarse-grained molecular dynamics simulation. PMB demonstrated characteristic preference to specific lipid species during its interaction with different membrane systems, such as the rough mutant lipipolysacchrides (Re LPS) preference in an outer membrane (OM) or the cardiolipin and POPG affinity in an inner membrane (IM). As a result of the lipid-specific actions, complicated membrane interaction states of PMB were observed, including adsorption on the OM surface. In contrast, for the IM or a mutative OM containing "impurity lipids" like POPE, POPG or lipid A, it could insert into the membrane via its acyl chain. Such actions of PMB influence the structure and lipid mobility of the membrane. In particular, the OM-bound PMB breaks the synchronous movement of Re LPS molecules in the outer leaflet and makes them diffuse more randomly, while its insertion into IM blocks the phospholipid diffusion and makes the membrane more homogeneous in the trajectory space. Our results provide insight into the action mechanism of PMB at a membrane level and a foundation for developing novel and safer polymyxin strategies for better clinical use.

Chiral carbon dots - a functional domain for tyrosinase Cu active site modulation via remote target interaction.

The nano-hybrid enzyme is an ideal catalytic system that integrates various advantages from biocatalysis and nanocatalysis into homogeneous and heterogeneous catalysis. However, great efforts are still needed to fully understand the interactions between nanoparticles and enzymes. Here, we show chiral carbon dots (CDs) as a new functional domain for tyrosinase Cu active site modulation via remote target interaction. Three kinds of chiral CDs (LCDs-1/-2/-3; DCDs-1/-2/-3) were fabricated by thermal treatment of citric acid and L/D-aspartic acid. Then a series of CDs/tyrosinase composites (namely, nano-hybrid-enzymes) were prepared, demonstrating good regulation of enzyme catalytic kinetics. Especially, we find that LCDs-1 is an irreversible inhibitor with great inhibition effect while the others are all reversible inhibitors. Furthermore, it is suggested by both experiments and all-atom molecular dynamics simulations that the joint effect of LCDs-1 and tyrosinase makes LCDs-1 serve as a new functional domain, which has a distinguished ability to control the conformational changes of the key sites of the active center of the tyrosinase (e.g., H60) and thus the escaping behavior of copper ions and the catalytic activity. This work opens a new route for nano-hybrid-enzyme design and enzyme activity regulation with chiral carbon materials as functional domains via remote target interaction.

[Effect of ischemia on the structure of bladder in rabbits with partial bladder outlet obstruction].

OBJECTIVE: To compare the structures and functions of rabbit bladder after partial bladder outlet obstruction versus without ischemia so as to explore the effects of ischemia on bladder pathogenesis in rabbits with partial bladder outlet obstruction. METHODS: A total of 64 mature male rabbits were divided into 4 groups (n = 16 each). Four of each group underwent operation to establish an ischemic animal model (ischemia group), another 4 underwent operation to establish a partial bladder outlet obstruction animal model (obstruct group), the other 4 underwent operation to establish an ischemic and partial bladder outlet obstruction animal model (combination group) and the remaining 4 underwent a sham operation as control. The rabbits in 4 groups were evaluated at Week 1, 2, 4 and 8 post-operation respectively. The weight of bladder, the thickness of mucosal, submucosa, muscular layer and placenta percreta and the activities of sarco/endoplasmic reticulum Ca(2+) ATPase citrate synthase of cystic smooth muscle were detected respectively. MASSON staining was used to observe the smooth muscle and collagen in stroma of bladder and S-100 staining for observing the neurons in bladder. RESULTS: In obstruct and combination groups, the weights of bladder at week 1 were (5.10 ± 0.29) g and (4.80 ± 0.37) g respectively. They were both significantly higher than control group [(1.93 ± 0.17) g, all P < 0.05]. The weights of bladder in obstruct and combination groups peaked at Week 4 and they were (18.48 ± 2.03) g and (12.35 ± 0.39) g respectively. The weight of bladder in obstruct group was significantly heavier than combination group in the same terms. And they were both significantly heavier than control and ischemia groups (all P < 0.05). Muscular tissue vicariously thickened during the first 4 weeks, and collagen and stroma increased at Week 4 in obstruct group. Muscular tissue, collagen and stroma all increased initially. But at Week 2 only collagen and stroma increased in combination group. Compare with control group, the other groups all have deletion of neurons, especially in combination group. The activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle of obstruct group peaked at Week 4. In combination group, the activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle were decreased over 2 - 8 weeks. In the same terms, the activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle in control group were significantly higher than those in obstruct and combination groups (all P < 0.05). CONCLUSION: Ischemia can reduce the tolerance of bladder and aggravate the impairment of bladder to partial outlet obstruction.

[Changes in prostatic stromal composition and benign prostatic hyperplasia].

OBJECTIVE: To investigate whether there are different stromal compositions in the prostate tissue of patients with benign prostatic hyperplasia (BPH) and evaluate their significance in the course of the disease. METHODS: Forty-three surgical or bioptic prostatic specimens of BPH and 5 autoptic normal prostatic specimens were stained by the Masson method to display the elements of the muscle fiber and collagen. The relationship of the changes in the prostatic stromal composition was analyzed with the degree of bladder outlet obstruction (BOO) , IPSS and medication results. RESULTS: The mean ratio of muscle fiber to collagen in the normal prostate tissue was (3.2 +/- 0.2):1, significantly higher than that of the BPH patients (1: [4.7 +/- 3.1] ) (P < 0.01); that in the BPH patients with BOO was 1: (5.4 +/- 3.7) markedly lower than in those without BOO (1: [2.5 +/- 1.1] ) (P = 0.02); that in the BPH patients with severe prostatic symptoms was 1: (9.1 +/- 2.9), remarkably lower than in those with moderate (1: [5.3 +/- 3.4]) and mild prostatic symptoms (1: [2.8 +/- 1.7]) (P < 0.01); and that in the BPH patients with satisfactory medicinal therapeutic results was 1:(2.3 +/- 1.9), significantly higher than in those with poor therapeutic results (1: [7.6 +/- 4.3]) (P < 0.01). CONCLUSION: The stromal composition in the prostatic tissue of BPH patients undergoes different degrees of changes. More obvious BPH symptoms and poorer therapeutic results are associated with a bigger proportion of collagens and a smaller proportion of muscle fibers in the prostatic tissue. These changes may play an important role in the development and progression of BPH.

Cardiolipin Selectively Binds to the Interface of VsSemiSWEET and Regulates Its Dimerization.

Lipid-regulated oligomerization of membrane proteins plays a critical role in many cell-transduction pathways. However, molecular details of such processes are often hard to define experimentally. Here we reveal the key role of interfacial cardiolipin in regulating the functional dimerization of VsSemiSWEET (one of the smallest transporters) using molecular dynamics simulations. Four binding sites for cardiolipins are identified by calculating the spatiotemporal density distribution of cardiolipins and the free energy surface. Two types of dimerization modes (i.e., arm-to-body and body-to-body) are observed in the assembly process of VsSemiSWEET protomers. Binding of enough cardiolipin molecules at the dimer interface on the cytoplasmic side is found to be crucial in adjusting the monomer-dimer equilibrium and regulating the formation of functional dimers with proper conformation. Our results provide useful information on the relationship between lipid binding and functional dimerization of VsSemiSWEET and are helpful to understand the molecular mechanism of biological function of sugar transporters.

[Arteriosclerotic risk factors and benign prostatic hyperplasia].

OBJECTIVE: To evaluate the correlation between arteriosclerotic risk factors and the severity of benign prostatic hyperplasia (BPH). METHODS: A total of 877 patients with diagnosed BPH were selected according to the inclusion criteria. The weight of the prostate was estimated by transrectal ultrasonography, the degree of bladder outlet obstruction determined by urodynamic examination, and the symptoms quantified by the International Prostate Symptom Score (IPSS). Arteriosclerotic risk factors included age, hypertension, dyslipidemia, type 2 diabetes mellitus, and smoking. Comparative studies were made on the data obtained by univariate and multivariate analyses. RESULTS: The severity of BPH was increased with the increase in the severity of the risk factors and the incidence of the disease. The logistic regression analysis showed that type 2 diabetes mellitus was a prominent predictor of the prostate volume, IPSS and degree of bladder outlet obstruction (OR = 3.179, 3.862 and 2.847, P < 0.001), while the level of serum triglyceride was not (P > 0.05). Age, hypertension, high LDL, low HDL and smoking were all prominent predictors of the severity of BPH. CONCLUSION: Arteriosclerotic risk factors are obviously correlated with the development and severity of BPH, among which type 2 diabetes mellitus is the most important.