Plasticity in single-crystalline Mg3Bi2 thermoelectric material.

Most of the state-of-the-art thermoelectric materials are inorganic semiconductors. Owing to the directional covalent bonding, they usually show limited plasticity at room temperature1,2, for example, with a tensile strain of less than five per cent. Here we discover that single-crystalline Mg3Bi2 shows a room-temperature tensile strain of up to 100 per cent when the tension is applied along the (0001) plane (that is, the ab plane). Such a value is at least one order of magnitude higher than that of traditional thermoelectric materials and outperforms many metals that crystallize in a similar structure. Experimentally, slip bands and dislocations are identified in the deformed Mg3Bi2, indicating the gliding of dislocations as the microscopic mechanism of plastic deformation. Analysis of chemical bonding reveals multiple planes with low slipping barrier energy, suggesting the existence of several slip systems in Mg3Bi2. In addition, continuous dynamic bonding during the slipping process prevents the cleavage of the atomic plane, thus sustaining a large plastic deformation. Importantly, the tellurium-doped single-crystalline Mg3Bi2 shows a power factor of about 55 microwatts per centimetre per kelvin squared and a figure of merit of about 0.65 at room temperature along the ab plane, which outperforms the existing ductile thermoelectric materials3,4.

Sequential absorption of two photons creates a bistable form of RubyACR responsible for its strong desensitization.

Channelrhodopsins with red-shifted absorption, rare in nature, are highly desired for optogenetics because light of longer wavelengths more deeply penetrates biological tissue. RubyACRs (Anion ChannelRhodopsins), a group of four closely related anion-conducting channelrhodopsins from thraustochytrid protists, are the most red-shifted channelrhodopsins known with absorption maxima up to 610 nm. Their photocurrents are large, as is typical of blue- and green-absorbing ACRs, but they rapidly decrease during continuous illumination (desensitization) and extremely slowly recover in the dark. Here, we show that long-lasting desensitization of RubyACRs results from photochemistry not observed in any previously studied channelrhodopsins. Absorption of a second photon by a photocycle intermediate with maximal absorption at 640 nm (P640) renders RubyACR bistable (i.e., very slowly interconvertible between two spectrally distinct forms). The photocycle of this bistable form involves long-lived nonconducting states (Llong and Mlong), formation of which is the reason for long-lasting desensitization of RubyACR photocurrents. Both Llong and Mlong are photoactive and convert to the initial unphotolyzed state upon blue or ultraviolet (UV) illumination, respectively. We show that desensitization of RubyACRs can be reduced or even eliminated by using ns laser flashes, trains of short light pulses instead of continuous illumination to avoid formation of Llong and Mlong, or by application of pulses of blue light between pulses of red light to photoconvert Llong to the initial unphotolyzed state.

Diversity of B Cell Populations and Ig Repertoire in Human Lungs.

The human lung carries a unique microbiome adapted to the air-filled, mucous-lined environment, the presence of which requires an immune system capable of recognizing harmful populations while preventing reactions toward commensals. B cells in the lung play a key role in pulmonary immunity, generating Ag-specific Abs, as well as cytokine secretion for immune activation and regulation. In this study, we compared B cell subsets in human lungs versus circulating cells by analyzing patient-paired lung and blood samples. We found a significantly smaller pool of CD19+, CD20+ B cells in the lung relative to the blood. CD27+, IgD-, class-switched memory B cells (Bmems) composed a larger proportion of the pool of pulmonary B cells. The residency marker CD69 was also significantly higher in the lung. We also sequenced the Ig V region genes (IgVRGs) of class-switched Bmems that do, or do not, express CD69. We observed the IgVRGs of pulmonary Bmems to be as heavily mutated from the unmutated common ancestor as those in circulation. Furthermore, we found progenies within a quasi-clone can gain or lose CD69 expression, regardless of whether the parent clone expressed the residency marker. Overall, our results show that despite its vascularized nature, human lungs carry a unique proportion of B cell subsets. The IgVRGs of pulmonary Bmems are as diverse as those in blood, and progenies of Bmems retain the ability to gain or lose residency.

Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Metal Variance in Multivariate Metal-Organic Frameworks for Boosting Catalytic Conversion of CO2.

Developing efficient, low-cost, MOF catalysts for CO2 conversion at low CO2 concentrations under mild conditions is particularly interesting but remains highly challenging. Herein, we prepared an isostructural series of two-dimensional (2D) multivariate metal-organic frameworks (MTV-MOFs) containing copper- and/or silver-based cyclic trinuclear complexes (Cu-CTC and Ag-CTC). These MTV-MOFs can be used as efficient and reusable heterogeneous catalysts for the cyclization of propargylamine with CO2. The catalytic performance of these MTV-MOFs can be engineered by fine-tuning the Ag/Cu ratio in the framework. Interestingly, the induction of 10% Ag remarkably improved the catalytic efficiency with a turnover frequency (TOF) of 243 h-1, which is 20-fold higher than that of 100% Cu-based MOF (i.e., TOF = 10.8 h-1). More impressively, such a bimetallic MOF still exhibited high catalytic activity even for simulated flue gas with 10% CO2 concentration. Furthermore, the reaction mechanism has been examined through the employment of NMR monitoring experiments and DFT calculations.

Direct Visualization of Molecular Stacking in Quasi-2D Hexagonal Ice.

Understanding ice nucleation and growth is of great interest to researchers due to its importance in the biological, cryopreservation, and environmental fields. However, microstructural investigations of ice on the molecular scale are still lacking. In this paper, a simple method is proposed to prepare quasi-2-dimensional ice Ih films, which have been characterized via cryogenic transmission electron microscope. The intersecting stacking faults of basal (BSF) and prismatic (PSF) types have been directly visualized and resolved with a notable first-time report of PSF in ice Ih. Moreover, the possible growth pathways of BSF, namely, the Ic phase, were elucidated by the theoretical calculations and the chair conformation of H2O molecules. This study offers valuable insights that can enhance researchers' understanding of the growth kinetics of crystalline ice.

Multifunctional Metal-Organic Frameworks as Catalysts for Tandem Reactions.

Owing to well-defined structure as well as easy synthesis and modification, metal-organic frameworks (MOFs) have emerged as promising catalysts for tandem reactions. In this article, we aim to summarize the development of multifunctional MOFs, including mixed metal MOFs, MOFs that are synergistically catalyzed by metal nodes and organic linkers, MOFs loaded with metal nanoparticles, etc, as heterogenous catalysts for tandem reactions over the past five years. This concept briefly discusses on present challenges, future trends, and prospects of multifunctional MOFs catalysts in tandem reactions.

Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.

This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.

Structural characterization and screening of chemical markers of alkaloids in Aconiti lateralis radix Praeparata and its processed products by UHPLC/Q-TOF-MS/MS and GNPS combining multivariate statistical methods based on the clinic.

RATIONAL: Aconiti Lateralis Radix Praeparata (AC) is a traditional Chinese medicine with a long history of use. However, the current research on the material basis of AC and its processed products is still not comprehensive, especially the changes in lipo-diterpenoid alkaloids (LDAs) that can be hydrolyzed into diester-diterpenoid alkaloids in AC before and after processing. This study aimed to provide material basis guidance for the clinical use of AC and its processed products by comprehensively analyzing the changes in substances between AC and its processed products. METHODS: An ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) approach was optimized to chemical profiling. The MS data were processed using molecular networking combined with the in-house library database to fast characterize the compounds. Multivariate statistical methods were adopted to determine the dissimilarities of components in AC and its processed products. RESULTS: A total of 310 compounds were tentatively identified from AC, including 109 potential new alkaloids, of which 98 were potential novel LPAs. A metabolomics approach was applied to find the characteristic marker components. As a result, 52 potential chemical markers were selected to distinguish the AC samples of different extraction methods and 42 potential chemical markers for differentiating between AC and its processed products were selected. CONCLUSION: The results indicate that UHPLC/Q-TOF-MS/MS and Global Natural Products Social Molecular Networking coupled with multivariate analysis strategies was a powerful tool to rapidly identify and screen the chemical markers of alkaloids between the AC samples and its processed products. These results also indicate that the toxicity of water extracts of AC and its processed products were decreased. This research not only guides the clinical safe use of AC and its processed products, but also extends the application of the molecular networking strategy in traditional herbal medicine.

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

An Explainable Artificial Intelligence Model to Predict Malignant Cerebral Edema after Acute Anterior Circulating Large-Hemisphere Infarction.

INTRODUCTION: Malignant cerebral edema (MCE) is a serious complication and the main cause of poor prognosis in patients with large-hemisphere infarction (LHI). Therefore, the rapid and accurate identification of potential patients with MCE is essential for timely therapy. This study utilized an artificial intelligence-based machine learning approach to establish an interpretable model for predicting MCE in patients with LHI. METHODS: This study included 314 patients with LHI not undergoing recanalization therapy. The patients were divided into MCE and non-MCE groups, and the eXtreme Gradient Boosting (XGBoost) model was developed. A confusion matrix was used to measure the prediction performance of the XGBoost model. We also utilized the SHapley Additive exPlanations (SHAP) method to explain the XGBoost model. Decision curve and receiver operating characteristic curve analyses were performed to evaluate the net benefits of the model. RESULTS: MCE was observed in 121 (38.5%) of the 314 patients with LHI. The model showed excellent predictive performance, with an area under the curve of 0.916. The SHAP method revealed the top 10 predictive variables of the MCE such as ASPECTS score, NIHSS score, CS score, APACHE II score, HbA1c, AF, NLR, PLT, GCS, and age based on their importance ranking. CONCLUSION: An interpretable predictive model can increase transparency and help doctors accurately predict the occurrence of MCE in LHI patients not undergoing recanalization therapy within 48 h of onset, providing patients with better treatment strategies and enabling optimal resource allocation.

Systematical Investigation on Anti-Fatigue Function and Underlying Mechanism of High Fischer Ratio Oligopeptides from Antarctic Krill on Exercise-Induced Fatigue in Mice.

High Fischer ratio oligopeptides (HFOs) have a variety of biological activities, but their mechanisms of action for anti-fatigue are less systematically studied at present. This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism of action through establishing the fatigue model of endurance swimming in mice. Therefore, according to the comparison with the endurance swimming model group, HFOs-AK were able to dose-dependently prolong the endurance swimming time, reduce the levels of the metabolites (lactic acid, blood urea nitrogen, and blood ammonia), increase the content of blood glucose, muscle glycogen, and liver glycogen, reduce lactate dehydrogenase and creatine kinase extravasation, and protect muscle tissue from damage in the endurance swimming mice. HFOs-AK were shown to enhance Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities and increase ATP content in muscle tissue. Meanwhile, HFOs-AK also showed significantly antioxidant ability by increasing the activities of superoxide dismutase and glutathione peroxidase in the liver and decreasing the level of malondialdehyde. Further studies showed that HFOs-AK could regulate the body's energy metabolism and thus exert its anti-fatigue effects by activating the AMPK signaling pathway and up-regulating the expression of p-AMPK and PGC-α proteins. Therefore, HFOs-AK can be used as an auxiliary functional dietary molecules to exert its good anti-fatigue activity and be applied to anti-fatigue functional foods.

The role of microRNAs in the regulation of critical genes and signalling pathways that determine endometrial receptivity.

Endometrial receptivity is the ability of the endometrium to accept embryos. Thus, endometrial receptivity dysfunction is an important factor leading to embryo implantation failure. A good endometrial receptivity provides a suitable environment for embryo implantation, improving the embryo implantation rate. The "implantation window" stage, or the receptive stage of the endometrium, is regulated by various hormones, genes, proteins and cytokines, among which microRNAs (miRNAs) and their target genes have a regulatory effect on endometrial receptivity. This review outlines the relationship between endometrial receptivity and pregnancy, the mRNAs and related signalling pathways that regulate endometrial receptivity, and the regulatory role of miRNA in endometrial receptivity, providing a deeper understanding of the regulatory mechanisms of miRNA on endometrial receptivity in humans and animals and reference for the endometrial receptivity-related research.

New polyketides from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2.

One new rare carbon-bridged citrinin dimer quinocitrindimer C (1) as a pair of epimers, two new polyketide penicilliodes D (3) and E (4) together with nine known citrinin derivatives, were isolated from the fermentation broth of starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Their structures and configurations were elucidated by comprehensively spectroscopic data analysis and electronic circular dichroism calculations. Eleven citrinin derivatives were tested by Colletotrichum gloeosporioides, and compound 2 played a significant antifungal activity against Colletotrichum gloeosporioides with LC50 value of 0.27 µg/ml.

The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment.

The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.

An Umbrella Insight into the Phytochemistry Features and Biological Activities of Corn Silk: A Narrative Review.

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.

[Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the incidence and risk factors of deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA). METHODS: The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed, including demographic characteristics, concomitant diseases, laboratory examinations (blood routine, biochemistry, coagulation, inflammatory markers, rheumatoid factor, antiphospholipid antibodies and lupus anticoagulant, etc.) and treatment regimens. The patients were compared according to the presence or absence of DVT, and the t test, Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT, followed by Logistic regression analysis to determine risk factors for DVT in patients with RA. RESULTS: The incidence of DVT in the RA patients was 9.6% (31/322); the median age of RA in DVT group was significantly older than that in non-DVT group [64 (54, 71) years vs. 50 (25, 75) years, P < 0.001]; the level of disease activity score using 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) in DVT group was higher than that in non-DVT group [5.2 (4.5, 6.7) vs. 4.5(4.5, 5.0), P < 0.001]; the incidence of hypertension, chronic kidney disease, fracture or surgery history within 3 months, and varicose veins of the lower extremities in DVT group was higher than that in non-DVT group (P < 0.001). The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group (P=0.009, P=0.004), while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group (P < 0.001). The use rate of glucocorticoid in DVT group was higher than that in non-DVT group (P=0.009). Logistic regression analysis showed that the age (OR=1.093, P < 0.001), chronic kidney disease (OR=7.955, P=0.005), fracture or surgery history within 3 months (OR=34.658, P=0.002), DAS28-ESR (OR=1.475, P=0.009), and the use of glucocorticoid (OR=5.916, P=0.003) were independent risk factors for DVT in RA patients. CONCLUSION: The incidence of DVT in hospitalized RA patients was significantly increased, in addition to traditional factors, such as age and chronic kidney disease, increased DAS28-ESR level and the use of glucocorticoid were also independent risk factors for DVT.

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles.

A convenient and efficient method for the synthesis of optically active difluoro-substituted indoline derivatives starting from the corresponding 3H-indoles by chiral phosphoric acid-catalyzed transfer hydrogenation was developed. Using Hantzsch ester as the hydrogen source under mild reaction conditions, the target products can be obtained with excellent yield and enantioselectivity.

Enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase is essential for the production of DHA in zebrafish.

Compared with other species, freshwater fish are more capable of synthesizing DHA via same biosynthetic pathways. Freshwater fish have a "Sprecher" pathway to biosynthesize DHA in a peroxisome-dependent manner. Enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh) is involved in the hydration and dehydrogenation reactions of fatty acid ß-oxidation in peroxisomes. However, the role of Ehhadh in the synthesis of DHA in freshwater fish remains largely unclear. In this study, the knockout of Ehhadh significantly inhibited DHA synthesis in zebrafish. Liver transcriptome analysis showed that Ehhadh deletion significantly inhibited SREBF and PPAR signaling pathways and decreased the expression of PUFA synthesis-related genes. Our results from the analysis of transgenic zebrafish (Tg:Ehhadh) showed that Ehhadh overexpression significantly increased the DHA content in the liver and significantly upregulated the expression of genes related to PUFA synthesis. In addition, the DHA content in the liver of Tg:Ehhadh fed with linseed oil was significantly higher than that of wildtype, but the expression of PUFA synthesis-related genes fads2 and elovl2 were significantly lower, indicating that Ehhadh had a direct effect on DHA synthesis. In conclusion, our results showed that Ehhadh was essential for DHA synthesis in the "Sprecher" pathway, and Ehhadh overexpression could promote DHA synthesis. This study provides insight into the role of Ehhadh in freshwater fish.

Recombinase-mediated gene stacking in cotton.

Site-specific gene stacking could reduce the number of segregating loci and expedite the introgression of transgenes from experimental lines to field lines. Recombinase-mediated site-specific gene stacking provides a flexible and efficient solution, but this approach requires a recombinase recognition site in the genome. Here, we describe several cotton (Gossypium hirsutum cv. Coker 312) target lines suitable for Mycobacteriophage Bxb1 recombinase-mediated gene stacking. Obtained through the empirical screening of random insertion events, each of these target lines contains a single intact copy of the target construct with precise sequences of RS2, lox, and attP sites that is not inserted within or close to a known gene or near a centromere and shows good expression of the reporter gene gfp. Gene stacking was tested with insertion of different combinations of three candidate genes for resistance to verticillium wilt into three cotton target lines: CTS1, CTS3, and CTS4. Nine site-specific integration events were recovered from 95 independently transformed embryogenic calluses. Southern and DNA sequence analyses of regenerated plants confirmed precise site-specific integration, and resistance to verticillium wilt was observed for plant CTS1i3, which has a single precise copy of site-specifically integrated DNA. These cotton target lines can serve as foundation lines for recombinase-mediated gene stacking to facilitate precise DNA integration and introgression to field cultivars.