Multi-pathways-mediated mechanisms of selenite reduction and elemental selenium nanoparticles biogenesis in the yeast-like fungus Aureobasidium melanogenum I15.

Selenium (Se) plays a critical role in diverse biological processes and is widely used across manufacturing industries. However, the contamination of Se oxyanions also poses a major public health concern. Microbial transformation is a promising approach to detoxify Se oxyanions and produce elemental selenium nanoparticles (SeNPs) with versatile industrial potential. Yeast-like fungi are an important group of environmental microorganisms, but their mechanisms for Se oxyanions reduction remain unknown. In this study, we found that Aureobasidium melanogenum I15 can reduce 1.0 mM selenite by over 90% within 48 h and efficiently form intracellular or extracellular spherical SeNPs. Metabolomic and proteomic analyses disclosed that A. melanogenum I15 evolves a complicated selenite reduction mechanism involving multiple metabolic pathways, including the glutathione/glutathione reductase pathway, the thioredoxin/thioredoxin reductase pathway, the siderophore-mediated pathway, and multiple oxidoreductase-mediated pathways. This study provides the first report on the mechanism of selenite reduction and SeNPs biogenesis in yeast-like fungi and paves an alternative avenue for the bioremediation of selenite contamination and the production of functional organic selenium compounds.

A Conserved Intramolecular Ion-Pair Plays a Critical but Divergent Role in Regulation of Dimerization and Transport Function among the Monoamine Transporters.

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters. The disruption of the ion-pair interactions by mutations induced a significant spontaneous cross-linking of a cysteine mutant of SERT and an increase in cell surface expression but with an impaired specific transport activity. On the other hand, similar mutations of the corresponding ion-pair residues in both DAT and NET resulted in an opposite effect on their oxidation-induced dimerization, cell surface expression, and transport function. Reversible biotinylation experiments indicated that the ion-pair mutations slowed down the internalization of SERT but stimulated the internalization of DAT. In addition, cysteine accessibility measurements for monitoring SERT conformational changes indicated that substitution of the ion-pair residues resulted in profound effects on the rate constants for cysteine modification in both the extracellular and cytoplasmatic substrate permeation pathways. Furthermore, molecular dynamics simulations showed that the ion-pair mutations increased the interfacial interactions in a SERT dimer but decreased it in a DAT dimer. Taken together, we propose that the transport function is modulated by the equilibrium between monomers and dimers on the cell surface, which is regulated by a potential compensatory mechanism but with different molecular solutions among the monoamine transporters. The present study provided new insights into the structural elements regulating the transport function of the monoamine transporters through their dimerization.

Bi-path color tunable plasmonic micro-nano hybrid structures for encrypted printing.

Colored information is crucial for humans to perceive the world. Plasmonic spectra modulation can serve as an effective means to create different colors. Although several solutions for plasmonic color-printing have been proposed, further information encryption has not received any attention. Herein, we exhibit a fine color modulation strategy to construct noble-metal-based micro-nano hybrid structures in the bi-path of photo-thermal deformation and liquid-phase-chemical reaction. Ag/Ta2O5 bi-layer films are ablated at the center of the machined lines of nanosecond pulsed laser, while silver nanoparticles are formed in other regions by thermal radiation of the infrared laser, which can be further dissolved and shape-modulated in KCl solution under different periods. The variation of size and spacing of nano-Ag particles results in a precise shift of plasmonic spectra in visible region. Colored information can be hidden by adjusting the scan number and the energy density during laser processing, and will emerge after the subsequent chemical dissolution reactions. The bi-path color adjustment strategy is easy to operate and can play a role in key information protection and color image switching.

Discovery and development of novel 10,12-disubstituted aloperine derivatives against HCoV-OC43 by targeting allosteric site of host TMPRSS2.

By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC50 values of 4.7 and 4.1 µM. A mechanism study revealed that it inhibited the protease activity of host TMPRSS2 by binding to an allosteric site, rather than the known catalytic center, different from that of camostat. Also, the combination of compound 3i and molnupiravir, as an RdRp inhibitor, showed an additive antiviral effect against HCoV-OC43. The results provide a new binding mode and lead compound for targeting TMPRSS2, with an advantage in combating broad-spectrum coronavirus.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.

Erratum: Author correction to 'Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects' [Acta Pharmaceutica Sinica B 13 (2023) 2138-2151].

[This corrects the article DOI: 10.1016/j.apsb.2022.12.009.].

Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications.

Prostate cancer is the second most prevalent cancer in men globally. De novo neuroendocrine prostate cancer (NEPC) is uncommon at initial diagnosis, however, (treatment-induced) t-NEPC emerges in up to 25% of prostate adenocarcinoma (PRAD) cases treated with androgen deprivation, carrying a drastically poor prognosis. The transition from PRAD to t-NEPC is underpinned by several key genetic mutations; TP53, RB1, and MYCN are the main genes implicated, bearing similarities to other neuroendocrine tumours. A broad range of epigenetic alterations, such as aberrations in DNA methylation, histone post-translational modifications, and non-coding RNAs, may drive lineage plasticity from PRAD to t-NEPC. The clinical diagnosis of NEPC is hampered by a lack of accessible biomarkers; recent advances in liquid biopsy techniques assessing circulating tumour cells and ctDNA in NEPC suggest that the advent of non-invasive means of monitoring progression to NEPC is on the horizon. Such techniques are vital for NEPC management; diagnosis of t-NEPC is crucial for implementing effective treatment, and precision medicine will be integral to providing the best outcomes for patients.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation.

We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from ∼7.1 to ∼1.7 nm, corresponding to a pulse-width-tuning range from ∼350 fs to ∼1.56 ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of ∼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.

Insights into the differential molecular response of non-germinated and germinated spores of Ameson portunus in vitro by comparative transcriptome analysis.

Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.

Differential molecular responses of hemolymph and hepatopancreas of swimming crab, Portunus trituberculatus, infected with Ameson portunus (Microsporidia).

Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.

Unique Substrate Recognition and Sodium-Substrate Binding Stoichiometry in a Bacterial Serotonin Transporter, TuriSERT.

All resolved high-resolution structures of the transporters in the neurotransmitter sodium symporter (NSS) family revealed that the NSS members share common structural and mechanistic features for substrate and ion binding and transport. However, a recently reported bacterial orthologue of the human serotonin transporter (hSERT), TuriSERT, possesses a structural characteristic specific for amino acid substrate binding but does transport a biogenic amine. The unique structural feature of TuriSERT requires a novel configuration for coordinating its substrate and ions. In the present study, we characterized TuriSERT expressed in Escherichia coli cells with a fluorescent substrate by biochemical, structural, and pharmacological approaches. Substrate transport by TuriSERT requires Na+ but not Cl-. Replacement of Asp262 by asparagine renders TuriSERT Cl--dependent. Substitutions of the corresponding Na1 residues did not alter Na+ dependence on substrate transport, whereas the mutation of a Na2 site residue led to a loss of transport activity, suggesting that Na+ binds only to the Na2 site in TuriSERT. In addition, substitutions of several residues essential for recognizing 5-hydroxytryptamine (5-HT) in hSERT had little effect on 5-HT displacement potency in transport assay for TuriSERT. In contrast, mutations of the residues that are proposed to coordinate with 5-HT in our docking model dramatically reduced 5-HT displacement. Furthermore, our results indicated that all tested antidepressants showed a weak inhibitory effect on TuriSERT. The present study demonstrated the existence of a unique substrate binding site and 1:1 stoichiometry of sodium-substrate binding in TuriSERT, a novel structural finding for the NSS transporters.

Research on the collapse characteristics of single cavitation bubble near solid particle by the VOF method.

In this paper, the collapse behavior of a single cavitation bubble at different distances near a solid particle of typical scales is numerically simulated and researched with the volume of fluid (VOF) method. Based on the key parameters analysis of the pressure field, velocity vector, collapse time the tendency of cavitation bubble collapse characteristics at different distances during the change of particle size is studied with the variable of the distance and relative size between the particle and the cavitation bubble. The dimensionless distance parameter 'γ' is specifically presented in the simulation process, the cavitation bubble collapse impact is largely directed to the particle when 3>γ > 2, while the wall hardly affects the interaction between the cavitation bubble and the solid particle as γ > 3. The results illustrate that as the solid particle and wall exist, the distance and particle size affect both the peak collapse pressure and the collapse jet velocity of the cavitation bubble, and the influence of solid wall on the cavitation bubble at the same distance is much greater than that of solid particles. When the particle size increases, the particle gradually affects the cavitation bubble in a way similar to the wall. While as the distance decreases or the particle size increases, the influence of particle and wall on the evolution process of the cavitation bubble expands, meanwhile, the collapse pressure and collapse jet velocity of the cavitation bubble are promoted with the optimized distance and particle size, which brings marvelous cavitation effect. The numerical methods and conclusions of this paper provide a valuable reference for cavitation applications of sand-containing fluids.

Semi-spontaneous temporal evolution of relief/fluorescence hybrid gratings for holographic encryption.

Holographic systems can reconstruct the entire wavefront of light which are developed as an excellent platform of information encryption. Although holography has utilized multiple modulation dimensions, little attention is given to its combination with fluorescence emitting. Herein, we propose a semi-spontaneous time-dependent encryption strategy of hybrid holographic fringes with surface relief and fluorescent emission mediated by a plasmonic polymer doped with fluorescent dyes. It is found that the two kinds of optical characteristic regions exhibit unique temporal evolution from the overlapped mode to the staggered one. The mode switching is closely related to the strong quenching effect of gold ions and nanoparticles which are dominant at the early and later recording stages, respectively. Thus, the real and deceptive information are recorded at different holographic writing periods. High-secret information of texts or images is constructed by the array of different sets of holographic fringes and is identified by comparing the dual-channel results of confocal laser scanning microscopes. This work puts a bright way to dynamic holographic encryption.

Activation of 2D titanate nanosheet photocatalysts by nitrogen doping and solution plasma processing.

Novel two-dimensional (2D) oxides are of great interest for photocatalysis because of their superlative physical features, namely, large surface areas, short charge diffusion pathways, high crystallinity and easy surface modification. However, most 2D oxides suffer from weak visible light absorption and severe photogenerated carrier recombination. Nitrogen doping can successfully narrow the bandgap of 2D oxides but can hardly improve the charge separation. In this work, we pre-dope nitrogen into 2D titanate nanosheets (HTiO), followed by surface processing with solution plasma. By dual modification of nitrogen doping and solution plasma processing (SPP), the modified 2D titanate nanosheets (N-HTiO-SPP) display broad absorption extending to the visible light region and the healing of oxygen vacancies brought about by nitrogen doping. Compared with HTiO and nitrogen doped titanate (N-HTiO), a higher removal rate and mineralization rate towards the photocatalytic degradation of acetaldehyde were achieved over N-HTiO-SPP under solar light. This work provides a powerful way to activate 2D wide bandgap semiconductors for enhanced photocatalytic activity.

First Natural Yeast Strain Trichosporon asahii HZ10 with Robust Flavonoid Productivity and Its Potential Biosynthetic Pathway.

Flavonoids are generally thought to be essential plant natural products with diverse bioactivities and pharmacological effects. Conventional approaches for the industrial production of flavonoids through plant extraction and chemical synthesis face serious economic and environmental challenges. Searching for natural robust flavonoid-producing microorganisms satisfying green and sustainable development is one of the good alternatives. Here, a natural yeast, Trichosporon asahii HZ10, isolated from raw honeycombs, was found to accumulate 146.41 mg/L total flavonoids intracellularly. Also, T. asahii HZ10 represents a broad flavonoid metabolic profiling, covering 40 flavonoids, among which nearly half were silibinin, daidzein, and irigenin trimethyl ether, especially silibinin occupying 21.07% of the total flavonoids. This is the first flavonoid-producing natural yeast strain worldwide. Furthermore, T. asahii HZ10-derived flavonoids represent favorable antioxidant activities. Interestingly, genome mining and transcriptome analysis clearly showed that T. asahii HZ10 possibly evolves a novel flavonoid synthesis pathway for the most crucial step of flavonoid skeleton synthesis, which is different from that in plants and filamentous fungi. Therefore, our results not only enrich the diversity of the natural flavonoid biosynthesis pathway but also pave an alternative way to promote the development of a synthetic biology strategy for the microbial production of flavonoids.

Role of Txnrd3 in NiCl2-induced kidney cell apoptosis in mice: Potential therapeutic effect of melatonin.

Nickel (Ni) exposure is a significant risk factor for kidney dysfunction and oxidative stress injury in humans. Thioredoxin reductase 3 (Txnrd3), an important enzyme in animals, plays a role in maintaining cellular homeostasis and regulating oxidative stress. However, its protective effect against kidney injury has been determined. Melatonin (Mel) has antioxidant and anti-apoptotic effects and therefore may be a preventive and therapeutic agent for kidney injury. Our study aimed to investigate the roles of Mel and Txnrd3 in the treatment of nickel-induced renal injury. We divided 80 wild-type mice and 80 Txnrd3 -/- mice (C57BL/6 N) into a control group treated with saline, Ni group treated with 10 mg/kg NiCl2, Mel group treated with 2 mg/kg Mel, and Ni + Mel group given NiCl2 and Mel for 21 days. Histopathological and ultrastructural observation of the kidney showed that nuclei were wrinkled and mitochondrial cristae were broken in the Ni group, and these changes were significantly attenuated by Mel treatment. Mitochondrial and nuclear damage improved significantly in the Ni + Mel and Txnrd3-/- Ni + Mel groups. Furthermore, NiCl2 exposure decreased T-AOC, SOD, and GSH activities in the kidney. The decreases in antioxidant enzyme activity were attenuated by Mel, and these improvements were abolished by Txnrd3 knockout. NiCl2-induced increases in the mRNA and protein levels of apoptosis factors (Bax, Cyt-c, caspase-3, and caspase-9) were attenuated by Mel treatment, and Txnrd3 knockout abolished the repressive effect of Mel on apoptosis genes. Overall, we concluded that Mel improves oxidative stress and apoptosis induced by NiCl2 by regulating Txnrd3 expression in the kidney. Our results provide evidence for the role of Mel in NiCl2-induced kidney injury and identify Txnrd3 as a potential therapeutic target for renal injury.

Association of C-type lectin-like receptor 2 and galectin-1 with portal vein system thrombosis in HBV-related liver cirrhosis.

Background and aims: Hepatitis B virus (HBV) infection is the most common cause of liver cirrhosis. Portal venous system thrombosis (PVST) is a major complication of liver cirrhosis. Recently, it has been shown that C-type lectin-like receptor 2 (CLEC-2) and galectin-1 participate in the activation and aggregation of platelets, thereby promoting the development of thrombosis. This cross-sectional study aims to evaluate the association of serum CLEC-2 and galectin-1 levels with PVST in patients with HBV-related liver cirrhosis. Methods: Overall, 65 patients with HBV-related liver cirrhosis were included, of whom 23 had PVST and 42 did not have. Serum CLEC-2 and galectin-1 levels were measured using enzyme-linked immunosorbent assay kits. PVST was assessed by contrast-enhanced computed tomography and/or magnetic resonance imaging scans. Subgroup analyses were conducted according to the degree and location of PVST. Results: Patients with PVST had significantly higher serum CLEC-2 (p = 0.006) and galectin-1 (p = 0.009) levels than those without. Patients with partial/complete PVST or fibrotic cord (p = 0.007; p = 0.002), but not those with mural PVST (p = 0.199; p = 0.797), had significantly higher serum CLEC-2 and galectin-1 levels than those without PVST. Patients with superior mesenteric vein thrombosis had significantly higher serum CLEC-2 (p = 0.013) and galectin-1 (p = 0.025) levels than those without PVST. Patients with main portal vein thrombosis had higher serum CLEC-2 (p = 0.020) and galectin-1 (p = 0.066) levels than those without PVST, but the difference in serum galectin-1 level was not significant between them. Conclusion: Serum CLEC-2 and galectin-1 levels may be associated with the presence of PVST in HBV-related cirrhotic patients, but this association should be dependent upon the degree of PVST.

Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.