Breeding of high-tolerance yeast by adaptive evolution and high-gravity brewing of mutant.

BACKGROUND: Ethanol and osmotic stresses are the major limiting factors for brewing strong beer with high-gravity wort. Breeding of yeast strains with high osmotic and ethanol tolerance and studying very-high-gravity (VHG) brewing technology is of great significance for brewing strong beer. RESULTS: This study used an optimized microbial microdroplet culture (MMC) system for adaptive laboratory evolution (ALE) of Saccharomyces cerevisiae YN81 to improve its tolerance to osmotic and ethanol stress. Meanwhile, we investigated the VHG and VHG with added ethanol (VHGAE) brewing processes for the evolved mutants in brewing strong beer. The results showed that three evolved mutants were obtained; among them, the growth performance of YN81mc-8.3 under 300, 340, 380, 420 and 460 g L-1 sucrose stresses was greater than that of the other strains. The ethanol tolerance of YN81mc-8.3 was 12%, which was 20% higher than that of YN81. During strong-beer brewing in a 100 L cylindrical cone-bottom tank, the sugar utilization and ethanol yield of YN81mc-8.3 outperformed those of YN81 in both the VHG and VHGAE brewing processes. Measurement of the diacetyl concentration showed that YN81mc-8.3 had a stronger diacetyl reduction ability; in particular, the real degree of fermentation of beers brewed by YN81mc-8.3 in VHG and VHGAE brewing processes was 75.35% and 66.71%, respectively - higher than those of the two samples brewed by YN81. Meanwhile, the visual, olfactive and gustative properties of the strong beer produced by YN81mc-8.3 were better than those of the other beers. CONCLUSION: In this study, the mutant YN81mc-8.3 and the VHGAE brewing process were optimal and represented a better alternative strong-beer brewing process. © 2023 Society of Chemical Industry.

A Fully Amorphous, Dynamic Cross-Linked Polymer Electrolyte for Lithium-Sulfur Batteries Operating at Subzero-Temperatures.

Solid-state lithium-sulfur batteries have shown prospects as safe, high-energy electrochemical storage technology for powering regional electrified transportation. Owing to limited ion mobility in crystalline polymer electrolytes, the battery is incapable of operating at subzero temperature. Addition of liquid plasticizer into the polymer electrolyte improves the Li-ion conductivity yet sacrifices the mechanical strength and interfacial stability with both electrodes. In this work, we showed that by introducing a spherical hyperbranched solid polymer plasticizer into a Li+ -conductive linear polymer matrix, an integrated dynamic cross-linked polymer network was built to maintain fully amorphous in a wide temperature range down to subzero. A quasi-solid polymer electrolyte with a solid mass content >90 % was prepared from the cross-linked polymer network, and demonstrated fast Li+ conduction at a low temperature, high mechanical strength, and stable interfacial chemistry. As a result, solid-state lithium-sulfur batteries employing the new electrolyte delivered high reversible capacity and long cycle life at 25 °C, 0 °C and -10 °C to serve energy storage at complex environmental conditions.

Refined Electrolyte and Interfacial Chemistry toward Realization of High-Energy Anode-Free Rechargeable Sodium Batteries.

Anode-free rechargeable sodium batteries represent one of the ultimate choices for the 'beyond-lithium' electrochemical storage technology with high energy. Operated based on the sole use of active Na ions from the cathode, the anode-free battery is usually reported with quite a limited cycle life due to unstable electrolyte chemistry that hinders efficient Na plating/stripping at the anode and high-voltage operation of the layered oxide cathode. A rational design of the electrolyte toward improving its compatibility with the electrodes is key to realize the battery. Here, we show that by refining the volume ratio of two conventional linear ether solvents, a binary electrolyte forms a cation solvation structure that facilitates flat, dendrite-free, planar growth of Na metal on the anode current collector and that is adaptive to high-voltage Na (de)intercalation of P2-/O3-type layered oxide cathodes and oxidative decomposition of the Na2C2O4 supplement. Inorganic fluorides, such as NaF, show a major influence on the electroplating pattern of Na metal and effective passivation of plated metal at the anode-electrolyte interface. Anode-free batteries based on the refined electrolyte have demonstrated high coulombic efficiency, long cycle life, and the ability to claim a cell-level specific energy of >300 Wh/kg.

Machine Learning Guided Discovery of Superoxide Dismutase Nanozymes for Androgenetic Alopecia.

Androgenetic alopecia (AGA) is a common form of hair loss, which is mainly caused by oxidative stress induced dysregulation of hair follicles (HF). Herein, a highly efficient manganese thiophosphite (MnPS3) based superoxide dismutase (SOD) mimic was discovered using machine learning (ML) tools. Remarkably, the IC50 of MnPS3 is 3.61 µg·mL-1, up to 12-fold lower than most reported SOD-like nanozymes. Moreover, a MnPS3 microneedle patch (MnMNP) was constructed to treat AGA that could diffuse into the deep skin where HFs exist and remove excess reactive oxygen species. Compared with the widely used minoxidil, MnMNP exhibits higher ability on hair regeneration, even at a reduced frequency of application. This study not only provides a general guideline for the accelerated discovery of SOD-like nanozymes by ML techniques, but also shows a great potential as a next generation approach for rational design of nanozymes.

Mitigating Electron Leakage of Solid Electrolyte Interface for Stable Sodium-Ion Batteries.

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

Insights into Anion-Solvent Interactions to Boost Stable Operation of Ether-Based Electrolytes in Pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 Full Cells.

Ether solvents with superior reductive stability promise excellent interphasial stability with high-capacity anodes while the limited oxidative resistance hinders their high-voltage operation. Extending the intrinsic electrochemical stability of ether-based electrolytes to construct stable-cycling high-energy-density lithium-ion batteries is challenging but rewarding. Herein, the anion-solvent interactions were concerned as the key point to optimize the anodic stability of the ether-based electrolytes and an optimized interphase was realized on both pure-SiOx anodes and LiNi0.8 Mn0.1 Co0.1 O2 cathodes. Specifically, the small-anion-size LiNO3 and tetrahydrofuran with high dipole moment to dielectric constant ratio realized strengthened anion-solvent interactions, which enhance the oxidative stability of the electrolyte. The designed ether-based electrolyte enabled a stable cycling performance over 500 cycles in pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 full cell, demonstrating its superior practical prospects. This work provides new insight into the design of new electrolytes for emerging high-energy density lithium-ion batteries through the regulation of interactions between species in electrolytes.

Noncoordinating Flame-Retardant Functional Electrolyte Solvents for Rechargeable Lithium-Ion Batteries.

In Li-ion batteries, functional cosolvents could significantly improve the specific performance of the electrolyte, for example, the flame retardancy. In case the cosolvent shows strong Li+-coordinating ability, it could adversely influence the electrochemical Li+-intercalation reaction of the electrode. In this work, a noncoordinating functional cosolvent was proposed to enrich the functionality of the electrolyte while avoiding interference with the Li storage process. Hexafluorocyclotriphosphazene, an efficient flame-retardant agent with proper physicochemical properties, was chosen as a cosolvent for preparing functional electrolytes. The nonpolar phosphazene molecules with low electron-donating ability do not coordinate with Li+ and thus are excluded from the primary solvation sheath. In graphite-anode-based Li-ion batteries, the phosphazene molecules do not cointercalate with Li+ into the graphite lattice during the charging process, which helps to maintain integral anode structure and interface and contributes to stable cycling. The noncoordinating cosolvent was also applied to other types of electrode materials and batteries, paving a new way for high-performance electrochemical energy storage systems with customizable functions.

Hierarchical structure and mechanical properties of fish scales from Lutjanidae with different habitat depths.

In recent days, many researchers are focusing on emerging a new class of bio-inspired architectured materials. The primary strategy of these architecture designs is directly dependent on the types of available literature based on higher-ordered species such as nacre and fish scales. In this study, the authors have investigated the microstructural features and mechanical properties of five different ray-finned fish scales from Lutjanidae family collected in Iran. It was found that habitat depth and habits may result in significant changes in scale's surface morphology and mechanical properties. Interestingly, the variations in cross-sectional microstructural features such as fibre orientation and layer thickness ratios in scales did not show noticeable differences. It has also been proved that the mechanical performance of fish scales is influenced by the shape, array pattern and compactness of strips on posterior edges in a scale. Moreover, the radii count at anterior positions is higher in fishes living in wide-ranging depth; it supports in achieving higher scale stiffness and flexibility during movement. Consideration of these factors may help in optimising the performance of newly designed architectured materials subjected to mechanical loadings.

Competitive Doping Chemistry for Nickel-Rich Layered Oxide Cathode Materials.

Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel-rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than BIII . In the case of Al-preoccupation, the bulk diffusion of BIII is hindered. In this way, a B-rich surface and Al-rich bulk is formed, which helps to synergistically stabilize the structural evolution and surface chemistry of the cathode.

The non-canonical functions of telomerase reverse transcriptase gene GlTert on regulating fungal growth, oxidative stress, and ganoderic acid biosynthesis in Ganoderma lucidum.

The telomerase reverse transcriptase (TERT) is the core catalytic subunit of telomerase. Its canonical function is synthesizing telomeric repeats to maintain telomere length and chromosomal stability. Accumulating evidence suggests that TERT has other important fundamental functions in addition to its catalytic telomere repeat synthesis activity. However, the non-canonical roles of TERT independent of its enzymatic activity are not clear in filamentous fungi. In the present study, we characterized the GlTert gene in Ganoderma lucidum. The non-canonical roles of GlTert were explored using GlTert-silenced strains (Terti8 and Terti25) obtained by RNA interference. Silencing GlTert delayed the fungal growth, decreased the length between hyphal branches, and induced fungal resistance to oxidative stress in G. ludicum. Further examination revealed that the intracellular ROS (reactive oxygen species) levels were increased while the enzyme activities of the antioxidant systems (superoxide dismutase, catalase, glutathione peroxidase, and ascorbate peroxidase) were decreased in GlTert-silenced strains. In addition, silencing GlTert decreased the ganoderic acid (GA) biosynthesis of G. lucidum. Taken together, our results indicate that GlTert plays a fundamental function on fungal growth, oxidative stress, and GA biosynthesis in G. lucidum, providing new insights for the canonical functions of TERT in filamentous fungi. KEY POINTS: • GlTert affected fungal growth and hyphal branching of G. lucidum. • Silencing GlTert increased the intracellular ROS levels of G. lucidum. • GlTert regulated GA biosynthesis of G. lucidum.

Combination of attenuated Salmonella carrying PD-1 siRNA with nifuroxazide for colon cancer therapy.

Colon cancer is a member of malignant tumors in the digestive system. Traditional treatment strategies are ineffective and improving the treatment of colon cancer is an urgent need. Targeting programmed cell death-1 (PD-1) by monoclonal antibodies has shown some therapeutic effectiveness and has advantages. Additionally, the Stat3 inhibitor nifuroxazide was employed to promote the antitumor activity. Here, we hypothesized that combining nifuroxazide with PD-1 small interfering RNA carried by attenuated Salmonella would exert a synergistic antitumor effect on colon cancer. Indeed, treatment with this combination effectively inhibited the development of colon cancer in mice and improved the survival rate. These two novel anticancer agents worked synergistically to elicit potent antitumor immunity and achieve improved therapeutic efficacy. The underlying mechanisms are mainly involved with immune regulation and cell apoptosis. This study provides a previous framework for combining this Stat3 inhibitor with RNAi designed to block immune checkpoint signaling for cancer therapy.

A case of vitiligo cured with cucumber and sulfur.

This study investigates a 42-year-old man who used sulfur powder adhered to cucumber slices to successfully self-treat a vitiligo condition. The treatment has resulted in no recurrence of the disease for 21 years. We analyzed the mechanism of this folk prescription for vitiligo, concluding that the success of the self-treatment may be mainly associated with hydrogen sulfide (H2 S). The antibacterial activity of pentathionic acid (H2 S5 O6 ) and the antioxidant activity of cucumber might also play a role in the treatment.

Pseudomonas sp. UW4 acdS gene promotes primordium initiation and fruiting body development of Agaricus bisporus.

To simplify industrial mushroom cultivation, we introduced a bacterial Pseudomonas sp. UW4 acdS gene, encoding 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase (AcdS), into fungus Agaricus bisporus. Transformant A. bisporus-acdS14 cased with sterilized-vermiculite generated primordia 5 days sooner than wild-type strain, confirming the specific role of the AcdS enzyme. Being consistent with the AcdS enzyme activity increased by 84%, the mycelium growth rate was increased by 25%; but, the ACC and ethylene concentrations were reduced by 71% and 36%, respectively, in the A. bisporus-acdS14 transformant. And the bacterium P. sp. UW4 attachment on the mycelium of the A. bisporus-acdS14 transformant was drastically reduced. We conclude that the heterogeneously expressed bacterial acdS gene degrades ACC and reduces ethylene-synthesis, eliminating ethylene inhibition on the mycelium growth and primordium formation in A. bisporus. Our results provide new insights into the mechanism underlying casing soil bacterium, and help formulate a casing-less cultivation for the next-generation mushroom industry.

The correlation between subendocardial viability ratio and the degree of coronary artery stenosis in patients with coronary heart disease and its predictive value for the incidence of short-term cardiovascular events.

OBJECTIVES: This study aimed to analyze the ability of subendocardial viability ratio (SEVR) to predict the degree of coronary artery stenosis and the relationship between SEVR and the incidence of short-term cardiovascular endpoint events. METHOD: The indexes of 243 patients with chest pain were collected.. Binary logistic regression analyses were performed using the dichotomous outcome of high and non-high SYNTAX scores. Receiver operating characteristic curves were employed to comparatively analyze the diagnostic efficiencies of the indices and models. A survival analysis combined with the Cox regression analysis was performed using the Kaplan-Meier method to understand the relationship between the SEVR and the incidence of cardiovascular events within 1 year in patients with coronary heart disease (CHD). RESULTS: SEVR was significantly lower (P < 0.05) in the high-stenosis group than control and low-stenosis groups. The diagnostic efficacy of SEVR [area under the curve (AUC) = 0.861] was better than those of age (AUC = 0.745), ABI (AUC = 0.739), and AIx@HR75 (AUC = 0.659). The cutoff SEVR was 1.105. In patients with confirmed CHD who had been discharged from the hospital for 1 year, only SEVR affected survival outcomes (hazard ratio = 0.010; 95% confidence interval: 0.001-0.418; P = 0.016). CONCLUSION: A significant decrease in SEVR predicted severe coronary artery stenosis, with a cutoff value of 1.105 and an accuracy of 0.861. In patients with CHD, the lower the SEVR, the higher was the rate of cardiovascular events at 1 year after hospital discharge.

Characteristics of exopolysaccharides from Paecilomyces hepiali and their simulated digestion and fermentation in vitro by human intestinal microbiota.

The metabolic process of polysaccharides in gastrointestinal digestions and the effects of the resulting carbohydrates on the composition of gut microbes are important to explore their prebiotic properties. Therefore, the purpose of this study was to investigate the simulated digestion and fecal fermentation in vitro of three fractions (PHEPSs-1, PHEPSs-2 and PHEPSs-3) purified from the crude exopolysaccharides of Paecilomyces hepiali HN1 (PHEPSs) and to explore the potential prebiotic mechanisms. The three purified fractions were characterized by HPLC, UV, FT-IR, SEM and AFM, and they were all of galactoglucomannan family with molecular weight of 178, 232 and 119 kDa, respectively. They could resist the simulated gastrointestinal digestions, but they were metabolized in fecal fermentation in vitro. Furthermore, the mannose in PHEPSs showed a higher utilization rate than that of glucose or galactose. The proliferation effects of PHEPSs on Bifidobacterium and Lactobacillus were weaker significantly than those of fructooligosaccharides before 12 h of fecal fermentation, but stronger after 24 h of fecal fermentation. Meanwhile, higher levels of short-chain fatty acids were found in PHEPSs groups when the fecal fermentation extended to 36 h. Therefore, PHEPSs are expected to have a potent gut healthy activity and can be explored as functional food ingredients.

Prospects and challenges of CAR-T cell therapy combined with ICIs.

Immune checkpoint molecules are a group of molecules expressed on the surface of immune cells that primarily regulate their immune homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology that realizes tumor-targeted killing by constructing synthetic T cells expressing specific antigens through biotechnology. Currently, CAR-T cell therapy has achieved good efficacy in non-solid tumors, but its treatment of solid tumors has not yielded the desired results. Immune checkpoint inhibitors (ICIs) combined with CAR-T cell therapy is a novel combination therapy with high expectations to defeat solid tumors. This review addresses the challenges and expectations of this combination therapy in the treatment of solid tumors.

[Effects of Different Modified Materials on Soil Fungal Community Structure in Saline-Alkali Soil].

Studying the effects of different modified materials on the physicochemical properties and fungal community structure of saline-alkali soil can provide theoretical basis for reasonable improvement of saline-alkali soil. High-throughput sequencing technology was used to explore the effects of five treatments, namely, control (CK), desulfurization gypsum (T1), soil ameliorant (T2), organic fertilizer (T3), and desulfurization gypsum compounds soil ameliorant and organic fertilizer (T4), on soil physicochemical properties and fungal community diversity, composition, and structure of saline-alkali soil in Hetao Plain, Inner Mongolia. The results showed that compared with those in CK, the contents of available phosphorus, available potassium, organic matter, and alkali hydrolysis nitrogen were significantly increased in modified material treatments, and the T4 treatment significantly decreased soil pH. Modified treatments increased the Simpson and Shannon indexes of fungi but decreased the Chao1 index. The dominant fungi were Ascomycota, Basidiomycota, and Mortierellomycota, and the dominant genera were Mortierella, Conocybe, Botryotrichum, Fusarium, and Pseudogymnoascus. The application of modified materials increased the relative abundance of Ascomycota, Basidiomycota, Fusarium, and Pseudogymnoascus, while decreasing the relative abundance of Mortierellomycota, Chytridiomycota, and Mortierella. LEfSe analysis showed that modified treatments altered the fungal community biomarkers. Correlation analysis showed that pH and available potassium were the main environmental factors affecting fungal community structure. The results can provide scientific basis for improving saline-alkali soil and increasing soil nutrients in Hetao Plain, Inner Mongolia.

Soil fungal community is more sensitive than bacterial community to modified materials application in saline-alkali land of Hetao Plain.

Soil salinization has become a major challenge that severely threatens crop growth and influences the productivity of agriculture. It is urgent to develop effective management measures to improve saline-alkali soil. Thus, in this study, soil properties, microbial communities, and function under desulfurization gypsum (DE), soil amendment (SA), farm manure (FA), and co-application of desulfurization gypsum, soil amendment, and farm manure (TA) in a field experiment were examined by high-throughput sequencing. The results showed that the application of modified materials is an effective approach in improving saline-alkali soil, especially TA treatment significantly increased the content of available phosphorus (AP), available potassium (AK), soil organic matter (SOM), and alkaline hydrolysis nitrogen (AHN) and decreased pH, bulk density (BD), and electrical conductivity (EC). The application of modified materials resulted in notable enhancement in fungal diversity and altered the composition and structure of the fungal community. Conversely, the effect on the bacterial community was comparatively minor, with changes limited to the structure of the community. Regarding the fungal community composition, Ascomycota, Mortierellomycota, and Basidiomycota emerged as the dominant phyla across all treatments. At each taxonomic level, the community composition exhibited significant variations in response to different modified materials, resulting in divergent soil quality. The TA treatment led to a decrease in Mortierellomycota and an increase in Ascomycota, potentially enhancing the ability to decompose organic matter and facilitate soil nutrient cycling. Additionally, the sensitivity of fungal biomarkers to modified materials surpassed that of the bacterial community. The impact of modified materials on soil microbial communities primarily stemmed from alterations in soil EC, AP, AK, and SOM. FUNGuild analysis indicated that the saprotroph trophic mode group was the dominant component, and the application of modified materials notably increased the symbiotroph group. PICRUSt analysis revealed that metabolism was the most prevalent functional module observed at pathway level 1. Overall, the application of modified materials led to a decrease in soil EC and an increase in nutrient levels, resulting in more significant alterations in the soil fungal community, but it did not dramatically change the soil bacterial community. Our study provides new insights into the application of modified materials in increasing soil nutrients and altering soil microbial communities and functions and provides a better approach for improving saline-alkali soil of Hetao Plain.

An ultralight, pulverization-free integrated anode toward lithium-less lithium metal batteries.

The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).

Spatiotemporal Dynamic Distribution, Regional Differences and Spatial Convergence Mechanisms of Carbon Emission Intensity: Evidence from the Urban Agglomerations in the Yellow River Basin.

Low-carbon transition is of great importance in promoting the high-quality and sustainable development of urban agglomerations in the Yellow River Basin (YRB). In this study, the spatial Markov chain and Dagum's Gini coefficient are used to describe the distribution dynamics and regional differences in the carbon emission intensity (CEI) of urban agglomerations in the YRB from 2007 to 2017. Additionally, based on the spatial convergence model, this paper analyzed the impact of technological innovation, industrial structure optimization and upgrading, and the government's attention to green development on the CEI's convergence speed for different urban agglomerations. The research results show that: (1) The probability of adjacent type transfer, cross-stage transfer, and cross-space transfer of the CEI of urban agglomerations in the YRB is small, indicating that the overall spatiotemporal distribution type of CEI is relatively stable. (2) The CEI of urban agglomerations in the YRB has decreased significantly, but the spatial differences are still significant, with a trend of continuous increase, and regional differences mainly come from the differences between urban agglomerations. (3) Expanding innovation output, promoting the optimization and upgrading of industrial structure, and enhancing the government's attention to green development has a significant positive effect on the convergence rate of the CEI of urban agglomerations in the YRB. This paper holds that implementing differentiated emission reduction measures and actively expanding regional collaborative mechanisms will play an important role in reducing the spatial differences in carbon emissions in urban agglomerations in the YRB, realizing the goals of peak carbon and carbon neutrality.