Field-tuned ferroquadrupolar quantum phase transition in the insulator TmVO4.

We report results of low-temperature heat-capacity, magnetocaloric-effect, and neutron-diffraction measurements of TmVO4, an insulator that undergoes a continuous ferroquadrupolar phase transition associated with local partially filled 4f orbitals of the thulium (Tm[Formula: see text]) ions. The ferroquadrupolar transition, a realization of Ising nematicity, can be tuned to a quantum critical point by using a magnetic field oriented along the c axis of the tetragonal crystal lattice, which acts as an effective transverse field for the Ising-nematic order. In small magnetic fields, the thermal phase transition can be well described by using a semiclassical mean-field treatment of the transverse-field Ising model. However, in higher magnetic fields, closer to the field-tuned quantum phase transition, subtle deviations from this semiclassical behavior are observed, which are consistent with expectations of quantum fluctuations. Although the phase transition is driven by the local 4f degrees of freedom, the crystal lattice still plays a crucial role, both in terms of mediating the interactions between the local quadrupoles and in determining the critical scaling exponents, even though the phase transition itself can be described via mean field. In particular, bilinear coupling of the nematic order parameter to acoustic phonons changes the spatial and temporal fluctuations of the former in a fundamental way, resulting in different critical behavior of the nematic transverse-field Ising model, as compared to the usual case of the magnetic transverse-field Ising model. Our results establish TmVO4 as a model material and electronic nematicity as a paradigmatic example for quantum criticality in insulators.

Electrostatic Gating of Spin Dynamics of a Quasi-2D Kagome Magnet.

Electrostatic gating has emerged as a powerful technique for tailoring the magnetic properties of two-dimensional (2D) magnets, offering exciting prospects including enhancement of magnetic anisotropy, boosting Curie temperature, and strengthening exchange coupling effects. Here, we focus on electrical control of the ferromagnetic resonance of the quasi-2D Kagome magnet Cu(1,3-bdc). By harnessing an electrostatic field through ionic liquid gating, significant shifts are observed in the ferromagnetic resonance field in both out-of-plane and in-plane measurements. Moreover, the effective magnetization and gyromagnetic ratios display voltage-dependent variations. A closer examination reveals that the voltage-induced changes can modulate magnetocrystalline anisotropy by several hundred gauss, while the impact on orbital magnetization remains relatively subtle. Density functional theory (DFT) calculations reveal varying d-orbital hybridizations at different voltages. This research unveils intricate physics within the Kagome lattice magnet and further underscores the potential of electrostatic manipulation in steering magnetism with promising implications for the development of spintronic devices.

Schlafen 5 suppresses human immunodeficiency virus type 1 transcription by commandeering cellular epigenetic machinery.

Schlafen-5 (SLFN5) is an interferon-induced protein of the Schlafen family, which are involved in immune responses and oncogenesis. To date, little is known regarding its anti-HIV-1 function. Here, the authors report that overexpression of SLFN5 inhibits HIV-1 replication and reduces viral mRNA levels, whereas depletion of endogenous SLFN5 promotes HIV-1 replication. Moreover, they show that SLFN5 markedly decreases the transcriptional activity of HIV-1 long terminal repeat (LTR) via binding to two sequences in the U5-R region, which consequently represses the recruitment of RNA polymerase II to the transcription initiation site. Mutagenesis studies show the importance of nuclear localization and the N-terminal 1-570 amino acids fragment in the inhibition of HIV-1. Further mechanistic studies demonstrate that SLFN5 interacts with components of the PRC2 complex, G9a and Histone H3, thereby promoting H3K27me2 and H3K27me3 modification leading to silencing HIV-1 transcription. In concert with this, they find that SLFN5 blocks the activation of latent HIV-1. Altogether, their findings demonstrate that SLFN5 is a transcriptional repressor of HIV-1 through epigenetic modulation and a potential determinant of HIV-1 latency.

Dietary supplementation with resistant starch contributes to intestinal health.

PURPOSE OF REVIEW: Resistant starch has received much attention recently as a healthy carbohydrate component of the diet. Resistant starch is not digested in the small intestine and can thus affect the gut microbiota of the host because of its fermentability. This review summarizes the interactions along the resistant starch-gut microbiota-host axis to help understand the health effects of resistant starch. RECENT FINDINGS: Recent studies indicate that resistant starch can be a helpful dietary component for special disease states like diabetes, metabolic syndrome, chronic kidney disease, constipation, and colitis. Its health effects are associated with modulation of the gut microbiota, and with gut microbes converting resistant starch into active and bioavailable metabolites that promote intestinal health. SUMMARY: The results from human clinical trials and studies in animal models indicate that supplementation of the diet with resistant starch in different metabolic diseases help remodel gut microbiota, especially increasing short-chain fatty acid (SCFA)-producing bacteria, and produce bioactive metabolites like SCFA, bile acids, and amino acids responsible for a variety of health effects. The gut microbiota and microbial metabolites probably mediate the effects of resistant starch on intestinal health.

Evidence of Magnon-Mediated Orbital Magnetism in a Quasi-2D Topological Magnon Insulator.

We explore spin dynamics in Cu(1,3-bdc), a quasi-2D topological magnon insulator. The results show that the thermal evolution of the Landé g factor (g) is anisotropic: gin-plane decreases while gout-of-plane increases with increasing temperature T. Moreover, the anisotropy of the g factor (Δg) and the anisotropy of saturation magnetization (ΔMs) are correlated below 4 K, but they diverge above 4 K. We show that the electronic orbital moment contributes to the g anisotropy at lower T, while the topological orbital moment induced by thermally excited spin chirality dictates the g anisotropy at higher T. Our work suggests an interplay among topology, spin chirality, and orbital magnetism in Cu(1,3-bdc).

Quasi-One-Dimensional Metallicity in Compressed CsSnI3.

Low-dimensional metal halides exhibit strong structural and electronic anisotropies, making them candidates for accessing unusual electronic properties. Here, we demonstrate pressure-induced quasi-one-dimensional (quasi-1D) metallicity in δ-CsSnI3. With the application of pressure up to 40 GPa, the initially insulating δ-CsSnI3 transforms to a metallic state. Synchrotron X-ray diffraction and Raman spectroscopy indicate that the starting 1D chain structure of edge-sharing Sn-I octahedra in δ-CsSnI3 is maintained in the high-pressure metallic phase while the SnI6 octahedral chains are distorted. Our experiments combined with first-principles density functional theory calculations reveal that pressure induces Sn-Sn hybridization and enhances Sn-I coupling within the chain, leading to band gap closure and formation of conductive SnI6 distorted octahedral chains. In contrast, the interchain I...I interactions remain minimal, resulting in a highly anisotropic electronic structure and quasi-1D metallicity. Our study offers a high-pressure approach for achieving diverse electronic platforms in the broad family of low-dimensional metal halides.

Freezing of the Lattice in the Kagome Lattice Heisenberg Antiferromagnet Zn-Barlowite ZnCu_{3}(OD)_{6}FBr.

We use ^{79}Br nuclear quadrupole resonance (NQR) to demonstrate that ultraslow lattice dynamics set in below the temperature scale set by the Cu-Cu superexchange interaction J (≃160 K) in the kagome lattice Heisenberg antiferromagnet Zn-barlowite. The lattice completely freezes below 50 K, and ^{79}Br NQR line shapes become twice broader due to increased lattice distortions. Moreover, the frozen lattice exhibits an oscillatory component in the transverse spin echo decay, a typical signature of pairing of nuclear spins by indirect nuclear spin-spin interaction. This indicates that some Br sites form structural dimers via a pair of kagome Cu sites prior to the gradual emergence of spin singlets below ∼30 K. Our findings underscore the significant roles played by subtle structural distortions in determining the nature of the disordered magnetic ground state of the kagome lattice.

Maize Root Exudates Recruit Bacillus amyloliquefaciens OR2-30 to Inhibit Fusarium graminearum Infection.

Bacillus spp. can exert plant growth-promoting effects and biocontrol effects after effective colonization, and bacterial chemotaxis toward plant root exudates is the initial step to colonize. Under biotic stress, plants are able to alter their root exudates to attract or avoid different types of microbes. Hence, Bacillus chemotaxis toward root exudates after pathogen infection is crucial for exerting their beneficial effects. In this study, the Bacillus amyloliquefaciens OR2-30 strain, which exhibited greater chemotaxis ability toward maize root exudates after Fusarium graminearum infection, was screened from 156 rhizosphere microorganisms. The infected maize root exudates were further confirmed to improve the swarming and biofilm formation ability of the OR2-30 strain. Chemotaxis, swarming, and biofilm formation ability were able to influence bacterial colonization. Indeed, the the OR2-30 strain displayed more effective colonization ability in the maize rhizosphere after F. graminearum inoculation. Moreover, lipopeptides produced by OR2-30 were identified as iturins and responsible for suppressing F. graminearum growth. Further study showed that lipopeptides suppressed the growth of F. graminearum by inhibiting conidia formation and germination, inducing reactive oxygen species production and causing cell death in mycelium. Eventually, the OR2-30 strain increased maize resistance against F. graminearum. These results suggested that maize root exudates could recruit B. amyloliquefacines OR2-30 after F. graminearum infection, and that OR2-30 then suppresses the F. graminearum by producing lipopeptides, such as iturins, to protect maize.

Design and Evaluation of Novel HIV-1 Protease Inhibitors Containing Phenols or Polyphenols as P2 Ligands with High Activity against DRV-Resistant HIV-1 Variants.

With the increasing prevalence of drug-resistant variants, novel potent HIV-1 protease inhibitors with broad-spectrum antiviral activity against multidrug-resistant causative viruses are urgently needed. Herein, we designed and synthesized a new series of HIV-1 protease inhibitors with phenols or polyphenols as the P2 ligands and a variety of sulfonamide analogs as the P2' ligands. A number of these new inhibitors showed superb enzymatic inhibitory activity and antiviral activity. In particular, inhibitors 15d and 15f exhibited potent enzymatic inhibitory activity in the low picomolar range, and the latter showed excellent activity against the Darunavir-resistant HIV-1 variant. Furthermore, the molecular modeling studies provided insight into the ligand-binding site interactions between inhibitors and the enzyme cavity, and they sparked inspiration for the further optimization of potent inhibitors.

Impact of the Lattice on Magnetic Properties and Possible Spin Nematicity in the S=1 Triangular Antiferromagnet NiGa_{2}S_{4}.

NiGa_{2}S_{4} is a triangular lattice S=1 system with strong two dimensionality of the lattice, actively discussed as a candidate to host spin-nematic order brought about by strong quadrupole coupling. Using Raman scattering spectroscopy we identify a phonon of E_{g} symmetry which can modulate magnetic exchange J_{1} and produce quadrupole coupling. Additionally, our Raman scattering results demonstrate a loss of local inversion symmetry on cooling, which we associate with sulfur vacancies. This will lead to disordered Dzyaloshinskii-Moriya interactions, which can prevent long-range magnetic order. Using magnetic Raman scattering response we identify 160 K as a temperature of an upturn of magnetic correlations. The temperature range below 160 K, but above 50 K where antiferromagnetic correlations start to increase, is a candidate for spin-nematic regime.

Microwave spectroscopy evidence of superconducting pairing in the magnetic-field-induced metallic state of InO(x) films at zero temperature.

We investigate the field-tuned quantum phase transition in a 2D low-disorder amorphous InO(x) film in the frequency range of 0.05 to 16 GHz employing microwave spectroscopy. In the zero-temperature limit, the ac data are consistent with a scenario where this transition is from a superconductor to a metal instead of a direct transition to an insulator. The intervening metallic phase is unusual with a small but finite resistance that is much smaller than the normal state sheet resistance at the lowest measured temperatures. Moreover, it exhibits a superconducting response on short length and time scales while global superconductivity is destroyed. We present evidence that the true quantum critical point of this 2D superconductor metal transition is located at a field B(sm) far below the conventionally defined critical field B(cross) where different isotherms of magnetoresistance cross each other. The superfluid stiffness in the low-frequency limit and the superconducting fluctuation frequency from opposite sides of the transition both vanish at B≈B(sm). The lack of evidence for finite-frequency superfluid stiffness surviving B(cross) signifies that B(cross) is a crossover above which superconducting fluctuations make a vanishing contribution to dc and ac measurements.

Relationship Between the Ovarian Cyst and Depression: A Two-Sample Mendelian Randomization Study.

Objective: Explore the causal relationship between the ovarian cyst and depression using a two-sample Mendelian randomization approach (MR). Methods: Based on data pooled from genome-wide association studies, genetic variants of the ovarian cyst and depression were selected as instrumental variables, as well as the Mendelian randomization analysis was conducted using inverse variance weighted (IVW) as the main analysis method and MR-Egger regression analysis, MR-PRESSO and other sensitivity analysis methods as supplements. Results: The IVW analysis showed a direct causal association between ovarian cysts and depression (OR=1.040; 95% CI: 1.003, 1.078; p=0.031). Meantime, there was a causal effect of genetically predicted depression on ovarian cysts (OR=1.327.; 95% CI: 1.197, 1.470; p<0.001). Sensitivity analyses such as MR-Egger regression analysis and MR-PRESSO indicated that the IVW results were robust and reliable. Conclusion: This study suggested since ovarian cysts and female depression are mutually causal, the comorbidity of ovarian cysts and depression in women should be actively attended to and given appropriate prevention and treatment besides the diagnosis and treatment of depression or ovarian cysts.

Bioactive polysaccharides promote gut immunity via different ways.

Numerous kinds of bioactive polysaccharides are identified as having intestinal immunomodulatory activity; however, the ways in which the different polysaccharides work differ. Therefore, we selected nine representative bioactive polysaccharides, including xanthan gum, inulin, guar gum, arabinogalactan, carrageenan, glucomannan, araboxylan, xylan, and fucoidan, and compared their intestinal immunomodulatory mechanisms. A cyclophosphamide (CTX)-induced immunosuppressed model was used in this experiment, and the effects of these polysaccharides on the number of T cells in the intestinal mucosa, expression of transcription factors and inflammatory factors, intestinal metabolome and gut microbiota were compared and discussed. The results revealed that the nine polysaccharides promote intestinal immunity in different ways. In detail, guar gum, inulin and glucomannan better alleviated immune suppression in intestinal mucosal T cells. Inulin improved the intestinal microenvironment by significantly upregulating the abundance of Lactobacillus and Monoglobus and promoted short chain fatty acid (SCFA) production. Fucoidan and carrageenan promoted the colonization of the beneficial bacteria Rikenella and Roseburia. In addition, fucoidan, inulin and carrageenan inhibited the colonization of harmful bacteria Helicobacter, upregulated the abundance of Clostridia_UCG-014 and alleviated the accumulation of amino acids, bile acids and indoles in the large intestine. In conclusion, our study uncovered the different intestinal immunomodulatory mechanisms of the different polysaccharides and provided a guideline for the development of superior intestinal immunomodulatory polysaccharides.

Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response.

The law and mechanism of the interaction between polysaccharides and pattern recognition receptors (PRRs) has been unclear. Herein, three glucomannans with different structures were selected to explore the universal mechanism for PRRs to recognize glucomannans. Screening results showed that the silence of TLR4 but not TLR2 severely blocked the production of inflammatory cytokines and the transduction of signal pathways. In-depth results revealed that the participation of myeloid differentiation protein 2 (MD2) and CD14 and the dimerization of the TLR4-MD2 complex were required for glucomannan-activated TLR4 signal transduction. Mannose receptor (MR) was also engaged in glucomannan-induced respiratory burst, endocytosis, and inflammatory signaling pathways in a spleen tyrosine kinase-dependent manner. The internalization of glucomannans into the cytoplasm by MR directly initiated complex intracellular signaling cascades. Finally, molecular docking characterized the binding energy and binding sites between glucomannans and multiple receptors from other perspectives. The essence of glucomannans recognized by PRRs was the non-covalent interaction of multiple receptors and the subsequent transmission of the signal cascade was triggered in a multi-channel and cooperative manner. As a result, the hypothesis that "Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response" was proposed to outline these meaningful phenomena.

Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota.

Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). The above results provided new insights into the hypolipidemic mechanism of TP and EGCG.

Stabilizing Au2+ in a mixed-valence 3D halide perovskite.

Although Cu2+ is ubiquitous, the relativistic destabilization of the 5d orbitals makes the isoelectronic Au2+ exceedingly rare, typically stabilized only through Au-Au bonding or by using redox non-innocent ligands. Here we report the perovskite Cs4AuIIAuIII2Cl12, an extended solid with mononuclear Au2+ sites, which is stable to ambient conditions and characterized by single-crystal X-ray diffraction. The 2+ oxidation state of Au was assigned using 197Au Mössbauer spectroscopy, electron paramagnetic resonance, and magnetic susceptibility measurements, with comparison to paramagnetic and diamagnetic analogues with Cu2+ and Pd2+, respectively, as well as to density functional theory calculations. This gold perovskite offers an opportunity to study the optical and electronic transport of the uncommon Au2+/3+ mixed-valence state and the characteristics of the elusive Au2+ ion coordinated to simple ligands. Compared with the perovskite Cs2AuIAuIIICl6, which has been studied since the 1920s, Cs4AuIIAuIII2Cl12 exhibits a 0.7 eV reduction in optical absorption onset and a 103-fold increase in electronic conductivity.

Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors.

The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein. Computation modeling predicts that these compounds interact with the residues in the receptor binding domain. More importantly, these teicoplanin derivatives inhibit the entry of both pseudotyped SARS-CoV-2 Delta and Omicron variants. Our study demonstrates the feasibility of developing small molecule entry inhibitors by targeting the interaction of viral S protein and ACE2. Together, considering the proven safety and pharmacokinetics of teicoplanin as a glycopeptide antibiotic, the teicoplanin derivatives hold great promise of being repurposed as pan-SARS-CoV-2 inhibitors.

Resistant starches and gut microbiota.

Resistant starches (RS), which are considered as one of the dietary fibers, could exert widely beneficial impacts, reduce fat accumulation, show significant effects on regulating blood glucose metabolism and insulin levels, and have protective effects on the gut. Five types of RS have different responses to chronic disease by modulating gut microbiota. Short-chain fatty acids are the linkage between gut microbiota and RS, and RS could improve the metabolism of gut microbiota as well as increase the abundance of beneficial microbes in the gut. The composition of gut microbiota is associated with RS properties, which is reflected by the changes of butyrate-producing bacteria primarily influenced by consumption of RS with various fine structures and types of crystallinities. RS with different fine structures and properties is consumed to varying degrees by gut microbiota, which can be applied to produce functional foods for gut health in future.

Interaction between polysaccharides and toll-like receptor 4: Primary structural role, immune balance perspective, and 3D interaction model hypothesis.

Various structural types of polysaccharides are recognized by toll-like receptor 4 (TLR4). However, the mechanism of interaction between the polysaccharides with different structures and TLR4 is unclarified. This review summarized the primary structure of polysaccharides related to TLR4, mainly including molecular weight, monosaccharide composition, glycosidic bonds, functional groups, and branched-chain structure. The optimal primary structure for interacting with TLR4 was obtained by the statistical analysis. Besides, the dual-directional regulation of TLR4 signaling cascade by polysaccharides was also elucidated from an immune balance perspective. Finally, the 3D interaction model of polysaccharides to TLR4-myeloid differentiation factor 2 (MD2) complex was hypothesized according to the LPS-TLR4-MD2 dimerization model and the polysaccharides solution conformation. The essence of polysaccharides binding to TLR4-MD2 complex is a multivalent non-covalent bond interaction. All the arguments summarized in this review are intended to provide some new insights into the interaction between polysaccharides and TLR4.

Biosynthesis of rumbrins and inspiration for discovery of HIV inhibitors.

Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets. The polyketide rumbrin (1) is a lipid peroxide production and calcium accumulation inhibitor, which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products. Here, we identify the biosynthetic gene cluster (BGC) rum of 1 and its isomer 12E-rumbrin (2) from Auxarthron umbrinum DSM3193, and elucidate their biosynthetic pathway based on heterologous expression, chemical complementation, and isotopic labeling. We show that rumbrins are assembled by a highly reducing polyketide synthase (HRPKS) that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit, and followed by methylation and chlorination. Sequent precursor-directed biosynthesis was able to yield a group of rumbrin analogues. Remarkably, inspired by the presence of a human immunodeficiency virus (HIV)-Nef-associated gene in the rum cluster, we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level. This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.