Hericium erinaceus polysaccharides ameliorate nonalcoholic fatty liver disease via gut microbiota and tryptophan metabolism regulation in an aged laying hen model.

Polysaccharides extracted from Hericium erinaceus (HEP) exhibit hepatoprotective activity in the alleviation of non-alcoholic fatty liver disease (NAFLD); however, the mechanisms underlying whether and how HEP regulation of the gut microbiota to alleviate liver-associated metabolic disorders are not well understood. This study used an aged laying hen model to explore the mechanisms through which HEP alleviates NAFLD, with a focus on regulatory function of HEP in the gut microbiome. The results showed that HEP ameliorated hepatic damage and metabolic disorders by improving intestinal barrier function and shaping the gut microbiota and tryptophan metabolic profiles. HEP increased the abundance of Lactobacillus and certain tryptophan metabolites, including indole-3-carboxylic acid, kynurenic acid, and tryptamine in the cecum. These metabolites upregulated the expression of ZO-1 and Occludin by activating the AhR and restoring the intestinal barrier integrity. The increased intestinal barrier functions decreased LPS transferring from the intestine to the liver, inhibited hepatic LPS/TLR4/MyD88/NF-κB pathway activation, and reduced hepatic inflammatory response and apoptosis. Fecal microbiota transplantation experiments further confirmed that the hepatoprotective effect is likely mediated by HEP-altered gut microbiota and their metabolites. Overall, dietary HEP could ameliorate the hepatic damage and metabolic disorders of NAFLD through regulating the "gut-liver" axis.

Polysaccharide from Hericium erinaceus improved laying performance of aged hens by promoting yolk precursor synthesis and follicle development via liver-blood-ovary axis.

Little information is available on the effect of Hericium erinaceus polysaccharides (HEP) on laying hens, especially on improving liver and ovarian health and function. Therefore, this study was conducted to investigate the impacts of HEP on liver and ovarian function to delay the decline in the laying performance of aged hens. A total of 360 fifty-eight-wk-old laying hens were randomly allocated to 4 treatments, with 6 replicates of 15 birds each. After 2 wk of adaptation, the birds were fed basal diet (CON) or basal diets supplemented with 250, 500, and 750 mg/kg of HEP (HEP250, HEP500, and HEP 750, respectively) for 12 wk. The results showed that, compared with CON, hens fed HEP had significantly increased laying performance (P < 0.05) and promoted follicle development, as evidenced by the increased numbers of hierarchical follicles, small follicles, and total follicles (P < 0.05). Birds fed 500 mg/kg of HEP improved the liver function by increasing T-AOC activity (P < 0.05) and decreasing hepatic oxidative stress and inflammatory responses (inflammatory cell infiltration) caused by aging. The lipid metabolism was improved, and yolk precursor synthesis was promoted in the liver of HEP-treated laying hens by upregulating the mRNA expression of FAS, MTTP, PPAR-α, APOVLDL-Ⅱ, and VTG-Ⅱ (P < 0.05). In addition, HEP significantly decreased ovarian inflammation by regulating the mRNA levels of NF-κB, IL-1ß, IL-6, and TNF-α (P < 0.05). As a result, the contents of E2, LH, and FSH in serum and the gene expression of ERα of the liver and FSHR of the ovary increased in HEP-treated hens (P < 0.05). In conclusion, dietary HEP supplementation exhibited potential hepatic and ovarian protective effects, thereby increasing the laying performance of aged hens by enhancing reproductive hormone secretion hormone secretion and promoting yolk precursor synthesis and follicle development via the liver-blood-ovary axis. The optimal supplementation level of HEP in aged hens was 500 mg/kg.

SDIPPWV: A novel hybrid prediction model based on stepwise decomposition-integration-prediction avoids future information leakage to predict precipitable water vapor from GNSS observations.

Water vapor is an important meteorological parameter. Accurate prediction of water vapor content can be used to provide important reference information for heavy rainfall forecast and artificial precipitation operation. The current water vapor hybrid prediction model has the problem of future data leakage, and the error is accumulated by reconstructing the subsequence after prediction. Therefore, this paper proposes a stepwise decomposition-integration-prediction precipitable water vapor mechanism, named SDIPPWV, which can effectively solve the above problems. Firstly, High-precision precipitable water vapor (PWV) sequence is retrieved from Global Navigation Satellite System (GNSS) observation files. Then stepwise decomposition process uses a fixed-size window to segment the PWV sequence and Seasonal-Trend decomposition based on Loess (STL) to decompose the sequences within the window. Next, the features of the three sub-sequences are integrated to construct the feature space. Finally the prediction of PWV is obtained using 1D Convolutional Neural Network-Bidirectional Long Short Term Memory (1D CNN-BiLSTM). The model performance is verified using observation data from eight GNSS stations. The performance of the PWV prediction model proposed in this paper is effectively improved compared with the single prediction models and other hybrid models. The mean root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE) and coefficient of determination (R2) of the eight stations are 0.2146 mm, 0.1132 mm, 1.29 %, and 0.9998, respectively. The results show that the model proposed in this paper improves the prediction accuracy of water vapor content while solving the data leakage problem.

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.

Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis.

The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.

Nitrogen Application Timing and Levels Affect the Fate and Budget of Fertilizer Nitrogen in the Apple-Soil System.

This study aimed to determine the effects of the nitrogen (N) application period and level on the fate of fertilizer N and the contribution of N absorption and translocation to apple organ N. Two N application periods (labeled by the 15N tracer technique in spring and summer, represented by SP and SU, respectively) and three N levels (N0, MN, and HN) were used to determine the physiological indexes and aboveground, root, and soil 15N content of 4-year-old dwarf ('Red Fuji'/M9T337) and arborized ('Red Fuji'/Malus hupehensis Rehd.) apple trees. The results showed that HN led to shoot overgrowth, which was not conducive to the growth of the apple root system (root length, root tips, root surface area, and root volume) or the improvement of root activity. The contribution of soil N to apple organ N accounted for more than 50%, and the contribution of N application in summer to fruit N was higher than that in spring. Under HN treatment, the proportion of soil N absorbed by trees decreased, while that of fertilizer N increased; however, the highest proportion was still less than 50%, so apple trees were highly dependent on soil N. Under MN treatment, fertilizer N residue was similar to soil N consumption, and soil N fertility maintained a basic balance. Under HN treatment, fertilizer N residue was significantly higher than soil N consumption, indicating that excessive N application increased fertilizer N residue in the soil. Overall, the 15N utilization rate of arborized trees (17.33-22.38%) was higher than that of dwarf trees (12.89-16.91%). A total of 12.89-22.38% of fertilizer 15N was absorbed by trees, 30.37-35.41% of fertilizer 15N remained in the soil, and 44.65-54.46% of fertilizer 15N was lost. The 15N utilization rate and 15N residual rate of summer N application were higher than those of spring N application, and the 15N loss rate was lower than that of spring N application. High microbial biomass N (MBN) may be one of the reasons for the high N utilization rate and the low loss rate of N application in summer.

Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound.

Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces a fragment-by-fragment growth RL forward molecular generation and optimization strategy based on a low activity lead compound. This process integrates fragment growth-based reaction templates, while target docking and drug-likeness prediction were simultaneously performed. This comprehensive approach considers molecular similarity, internal diversity, synthesizability, and effectiveness, thereby enhancing the quality and efficiency of molecular generation. Finally, a series of tyrosinase inhibitors were generated and synthesized. Most compounds exhibited more improved activity than lead, with an optimal candidate compound surpassing the effects of kojic acid and demonstrating significant antipigmentation activity in a zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural optimization strategies will play a promising role in accelerating the drug discovery and improving traditional efficiency.

Systematic review of the efficacy and safety of lenvatinib in various solid tumors.

OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. METHOD: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures. RESULTS: A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, p < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, p < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities. CONCLUSIONS: Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.

Taking spontaneous plants as a natural strategy for vegetation restoration in construction and demolition waste landfills: a case study in Suzhou, China.

Construction and demolition waste (CDW) landfills around the city have caused serious damage to the ecological environment and menaced the public health. Restoration of closed CDW landfills is critical to compensate for the degraded ecosystem and ensure safety in further development and utilization. Vegetation restoration is an essential part of the restoration of CDW landfills, in which the use of spontaneous plants is the foundation of the nature-based strategy. In this study, Fenghuangshan CDW landfill in Suzhou, China, was selected as the research site, and the species composition and diversity of the spontaneous plants were analyzed. Moreover, the types of habitats and growth indexes of 8 species with high frequency and 18 species with medium frequency in the CDW landfill were investigated, and a comprehensive evaluation of growth rate and expansion capacity of the 26 species was conducted. The results showed that, herbs were the main type of the spontaneous plants in the CDW landfill. The species and quantities of the spontaneous plants in the CDW landfill were obviously fewer than those in the surrounding areas of the CDW landfill, and the Shannon-Wiener index and Pielou index of the spontaneous plants were lower compared with the surrounding areas of the CDW landfill. Meanwhile, the differences of dominant families and the distribution of origins, life forms and growth types between these two fields were insignificant. The heliophilous and drought tolerance species were widely distributed in the CDW landfill while the shade-tolerant or hygrophilous species were few. The relatively large comprehensive evaluation indexes of Elymus dahuricus, Daucus carota, Sonchus asper, Geranium carolinianum, Rumex acetosa, Metaplexis japonica, Carex breviculmis, Erigeron canadensis, Trigonotis peduncularis, Lamium amplexicaule reflected their high growth rates and strong expansion capacity, demonstrating their great potentiality in the vegetation restoration of CDW landfills as indispensable components of the nature-based solution.

Detection of extreme hydrological droughts in the poyang lake basin during 2021-2022 using GNSS-derived daily terrestrial water storage anomalies.

Poyang Lake is the largest freshwater lake in China, serving as a natural reservoir and playing a paramount role in climate regulation, ecological environment, and water resource management. However, in recent years, Poyang Lake has approached desiccation multiple times, with severe droughts becoming increasingly common. Consequently, precise quantification and analysis of the terrestrial water storage anomalies (TWSA) and drought characteristics of the Poyang Lake basin (PLB) are of profound scientific and practical significance. This paper, for the first time, utilizes data for the period 2021-2022 from 77 newly-established GNSS observation stations in the PLB to precisely determine its vertical crustal displacement, invert daily and monthly TWSA, and investigate extreme hydrological drought. The results reveal the following: 1) The annual amplitude range of vertical surface displacements at GNSS stations in the Poyang Lake basin is from 7 to 14 mm, with the most substantial seasonal vertical displacements occurring during the months of June and July; 2) monthly GNSS-TWSA maintains a commendable consistency with TWSA data obtained from the Gravity Recovery and Climate Experiment (GRACE), the Global Land Data Assimilation System (GLDAS), and precipitation, with correlation coefficients of 0.67, 0.55, and 0.62, respectively; 3) at daily scale, the GNSS-derived Drought Severity Index (GNSS-DSI) accurately recorded the severity and intensity of eight drought events in the PLB during 2021-2022, in particular the period of extensive drought between October 2021 and February 2022, when drought intensity reaching a notable 1.03, which is classified as an extreme and prolonged drought event. Additionally, at local temporal scales, daily GNSS-DSI exhibits heightened sensitivity to drought signals. This study provides novel technological tools and datasets for multi-source satellite-based drought monitoring in the PLB.

Enabling Uniform and Stable Lithium-Ion Diffusion at the Ultrathin Artificial Solid-Electrolyte Interface in Siloxene Anodes.

Constructing a stable and robust solid electrolyte interphase (SEI) has a decisive influence on the charge/discharge kinetics of lithium-ion batteries (LIBs), especially for silicon-based anodes which generate repeated destruction and regeneration of unstable SEI films. Herein, a facile way is proposed to fabricate an artificial SEI layer composed of lithiophilic chitosan on the surface of two-dimensional siloxene, which has aroused wide attention as an advanced anode for LIBs due to its special characteristics. The optimized chitosan-modified siloxene anode exhibits an excellent reversible cyclic stability of about 672.6 mAh g-1 at a current density of 1000 mA g-1 after 200 cycles and 139.9 mAh g-1 at 6000 mA g-1 for 1200 cycles. Further investigation shows that a stable and LiF-rich SEI film is formed and can effectively adhere to the surface during cycling, redistribute lithium-ion flux, and enable a relatively homogenous lithium-ion diffusion. This work provides constructive guidance for interface engineering strategy of nano-structured silicon anodes.

Ultracold field-linked tetratomic molecules.

Ultracold polyatomic molecules offer opportunities1 in cold chemistry2,3, precision measurements4 and quantum information processing5,6, because of their rich internal structure. However, their increased complexity compared with diatomic molecules presents a challenge in using conventional cooling techniques. Here we demonstrate an approach to create weakly bound ultracold polyatomic molecules by electroassociation7 (F.D. et al., manuscript in preparation) in a degenerate Fermi gas of microwave-dressed polar molecules through a field-linked resonance8-11. Starting from ground-state NaK molecules, we create around 1.1 × 103 weakly bound tetratomic (NaK)2 molecules, with a phase space density of 0.040(3) at a temperature of 134(3) nK, more than 3,000 times colder than previously realized tetratomic molecules12. We observe a maximum tetramer lifetime of 8(2) ms in free space without a notable change in the presence of an optical dipole trap, indicating that these tetramers are collisionally stable. Moreover, we directly image the dissociated tetramers through microwave-field modulation to probe the anisotropy of their wavefunction in momentum space. Our result demonstrates a universal tool for assembling weakly bound ultracold polyatomic molecules from smaller polar molecules, which is a crucial step towards Bose-Einstein condensation of polyatomic molecules and towards a new crossover from a dipolar Bardeen-Cooper-Schrieffer superfluid13-15 to a Bose-Einstein condensation of tetramers. Moreover, the long-lived field-linked state provides an ideal starting point for deterministic optical transfer to deeply bound tetramer states16-18.

Correlation analysis between camrelizumab trough concentration levels and efficacy or safety in East Asian patients with advanced lung cancer.

BACKGROUND: Camrelizumab combined with chemotherapy is approved across tumor types. However, only a fraction of patients benefits from immunotherapy, and biomarkers such as the expression of PD-L1, tumor mutational burden, and CXCL11 are expensive and suboptimal specificity for cancer patients. An exposure-response (E-R) relationship has been reported in many immune checkpoint inhibitors (ICIs), and the trough concentrations and other drug exposure metrics are broadly used to guide dosing decisions, assess exposure-outcomes relationships, and ultimately predict outcomes based on those relationships. However, the potential use of trough concentration levels for camrelizumab is still not clear. METHODS: Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration. RESULTS: We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05). CONCLUSIONS: Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.

Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 µmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 µg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 µg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Discovery and bioassay of disubstituted ß-elemene-NO donor conjugates: synergistic enhancement in the treatment of leukemia.

Natural products are essential sources of antitumor drugs. One such molecule, ß-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor ß-elemene derivatives were designed, with ß-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.

Interactions between enzyme preparations and trace element sources on growth performance and intestinal health of broiler chicks.

This experiment was conducted to explore the interactions between enzyme preparations and trace element sources on growth performance and intestinal health of broilers chicks. A total of 480 one-day-old healthy male yellow-feather broilers with similar weight were randomly arranged in a 2  ×  2 factorial design with 2 kinds of compound trace element sources (inorganic [I] and organic [O] trace element supplemented with 80, 8, 60, 40, 0.15 mg/kg of Fe, Cu, Mn, Zn, and Se, respectively) and 2 levels of enzyme preparations (0 and 200 mg/kg). The 4 groups named I, O, IE, and OE with 6 replicates and 20 birds per replicate. The trail lasted for 28 days. Results showed that the average weight (ABW), average daily gain (ADG) of broilers in IE and OE groups significantly increased while the F/G significantly decreased as compared with group I and O (P < 0.05). Enzyme preparation supplementation, regardless of the trace element sources, significantly increased the duodenal and jejunal endogenous enzyme (e.g., Try and AACT) activity, and improved the morphology and jejunal barrier function evidenced by the increased villus height and MUC-2 mRNA expression (P < 0.05). Sequencing data manifested that enzyme preparations favorably modulated the cecal microflora by increasing bacterial diversity and abundance of short-chain fatty acid (SCFA)-producing bacteria (e.g., Anaerostipes, Anaerofusis, and Pygmaioactor), while decreasing the abundance of harmful bacteria (e.g., Desulfovibrio). Factorial analysis indicated that there were no interactions between enzyme preparation and trace element sources on growth performance and intestinal health of broiler chicks. In conclusion, dietary supplementation with enzyme preparations, regardless of the trace element sources, could enhance endogenous enzyme activity, improve intestinal morphology and barrier functions, and favorably modulate the cecal microflora, thereby improving the intestinal health and growth performance of broiler chicks.

Research progress of biomimetic materials in oral medicine.

Biomimetic materials are able to mimic the structure and functional properties of native tissues especially natural oral tissues. They have attracted growing attention for their potential to achieve configurable and functional reconstruction in oral medicine. Though tremendous progress has been made regarding biomimetic materials, significant challenges still remain in terms of controversy on the mechanism of tooth tissue regeneration, lack of options for manufacturing such materials and insufficiency of in vivo experimental tests in related fields. In this review, the biomimetic materials used in oral medicine are summarized systematically, including tooth defect, tooth loss, periodontal diseases and maxillofacial bone defect. Various theoretical foundations of biomimetic materials research are reviewed, introducing the current and pertinent results. The benefits and limitations of these materials are summed up at the same time. Finally, challenges and potential of this field are discussed. This review provides the framework and support for further research in addition to giving a generally novel and fundamental basis for the utilization of biomimetic materials in the future.

Mammalian trans-editing factor ProX is able to deacylate tRNAThr mischarged with alanine.

The precise coupling of tRNAs with their cognate amino acids, known as tRNA aminoacylation, is a stringently regulated process that governs translation fidelity. To ensure fidelity, organisms deploy multiple layers of editing mechanisms to correct mischarged tRNAs. Prior investigations have unveiled the propensity of eukaryotic AlaRS to erroneously attach alanine onto tRNACys and tRNAThr featuring the G4:U69 base pair. In light of this, and given ProXp-ala's capacity in deacylating Ala-tRNAPro, we embarked on exploring whether this trans-editing factor could extend its corrective function to encompass these mischarged tRNAs. Our in vitro deacylation assays demonstrate that murine ProXp-ala (mProXp-ala) is able to efficiently hydrolyze Ala-tRNAThr, while Ala-tRNACys remains unaffected. Subsequently, we determined the first structure of eukaryotic ProXp-ala, revealing a dynamic helix α2 involved in substrate binding. By integrating molecular dynamics simulations and biochemical assays, we pinpointed the pivotal interactions between mProXp-ala and Ala-tRNA, wherein the basic regions of mProXp-ala as well as the C3-G70 plays essential role in recognition. These observations collectively provide a cogent rationale for mProXp-ala's deacylation proficiency against Ala-tRNAThr. Our findings offer valuable insights into the translation quality control within higher eukaryotic organisms, where the fidelity of translation is safeguarded by the multi-functionality of extensively documented proteins.

Effect of Composition Adjustment on the Thermoelectric Properties of Mg3Bi2-Based Thermoelectric Materials.

Thermoelectric materials are widely used in refrigeration chips, thermal power generation, catalysis and other fields. Mg3Bi2-based thermoelectric material is one of the most promising thermoelectric materials. Herein, the Mg3Bi2-based samples were prepared by high temperature synthesis, and the influence of Mg/Sb content on the electrical transport properties and semi-conductivity/semi-metallicity of the materials has been studied. The results indicate that the efficiency of introducing electrons from excess Mg prepared by high temperature synthesis is lower than that introduced by ball milling, due to the high vapor pressure of Mg. The doping of Sb/Te at the Bi site would make it easier for the material to change from p-type conduction to n-type conduction. With the increase in Mg content, the semi-conductivity of the material becomes weaker, the semi-metallicity becomes stronger, and the corresponding conductivity increases. With the increase in Sb content, the samples exhibit the opposite changes. The highest power factor of ~1.98 mWm-1K-2 is obtained from the Mg3.55Bi1.27Sb0.7Te0.03 sample.

Study on the Targeted Improvement Mechanism of the Carrier Concentration and Mobility of BiCuSeO Ceramics.

BiCuSeO has great application prospects in thermoelectric power generation and thermoelectric catalysis, but it is limited by its lower thermoelectric performance. Herein, BiCuSeO bulk materials were prepared using a solid-phase reaction method and a ball-milling method combined with spark plasma sintering, and then the thermoelectric properties were improved by synergistically increasing carrier concentration and mobility. Al was adopted to dope into the BiCuSeO matrix, aiming to adjust the carrier mobility through energy band adjustment. The results show that Al doping would widen the bandgap and enhance the carrier mobility of BiCuSeO. After Al doping, the thermoelectric properties of the material are improved in the middle- and high-temperature range. Based on Al doping, Pb is adopted as the doping element to dope BiCuSeO to modify the carrier concentration. The results show that Al/Pb dual doping in the BiCuSeO matrix can increase the carrier concentration under the premise of increasing carrier mobility. Therefore, the electrical conductivity of BiCuSeO can be improved while maintaining a large Seebeck coefficient. The power factor of Al/Pb doping reached ~7.67 µWcm-1K-2 at 873 K. At the same time, the thermal conductivity of all doped samples within the test temperature range maintained a low level (<1.2 Wm-1K-1). Finally, the ZT value of the Al/Pb-doped BiCuSeO reached ~1.14 at 873 K, which is ~2.72 times that of the pure phase, and the thermoelectric properties of the matrix were effectively improved.