New potential selective estrogen receptor modulators in traditional Chinese medicine for treating menopausal syndrome.

Women go through several predictable conditions and symptoms during menopause that are caused by age, changes in sex hormone levels, and other factors. Conventional menopause hormone therapy has raised serious concerns about the increased risks of cancers, blood clots, depression, etc. Selective estrogen receptor modulators (SERMs) that can be both agonists and antagonists of estrogen receptors in a tissue-specific manner are being developed to reduce the health concerns associated with menopause hormone therapy. Here, we have searched the Chinese national traditional Chinese medicine (TCM) patent database to identify potential SERM-like compounds with reduced health risks. TCM has been widely used for treating complex symptoms associated with menopause syndrome and thus can be a particularly rich source for pharmaceutical alternatives with SERM properties. After extensive literature review and molecular simulation, we conclude that protopanaxatriol, paeoniflorin, astragalin, catalpol, and hyperoside among others may be particularly promising as SERM-like compounds in treating the menopausal syndrome. Compounds in TCM hold promise in yielding comparable outcomes to hormone therapy but with reduced associated risks, thus presenting promising avenues for their clinical applications.

Study on rock fracture mechanism and hydraulic fracturing propagation law of heterogeneous tight sandstone reservoir.

Hydraulic fracturing technology is an effective way to develop tight sandstone reservoirs with low porosity and permeability. The tight sandstone reservoir is heterogeneous and the heterogeneity characteristics has an important influence on fracture propagation. To investigate hydraulic fracture performance in heterogeneous tight reservoir, the X-ray diffraction experiments are carried out, the Weibull distribution method and finite element method are applied to establish the uniaxial compression model and the hydraulic fracture propagation model of heterogeneous tight sandstone. Meanwhile, the sensitivity of different heterogeneity characterization factors and the multi-fracture propagation mechanism during hydraulic fracture propagation is analyzed. The results indicate that the pressure transfer in the heterogeneous reservoir is non-uniform, showing a multi-point initiation fracture mode. For different heterogeneity characterization factors, the heterogeneity characteristics based on elastic modulus are the most sensitive. The multi-fracture propagation of heterogeneous tight sandstone reservoir is different from that of homogeneous reservoir, the fracture propagation morphology is more complex. With the increase of stress difference, the fracture propagation length increases. With the increase of injection rate, the fracture propagation length increases. With the increase of cluster spacing, the propagation length of multiple fractures tends to propagate evenly. This study clarifies the influence of heterogeneity on fracture propagation and provides some guidance for fracturing optimization of tight sandstone reservoirs.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Hormesis and synergistic effects of disinfectants chloroxylenol and benzethonium chloride on highly efficient heterotrophic nitrification-aerobic denitrification functional strain: From performance to mechanism.

The heterotrophic nitrification-aerobic denitrification (HNAD) strain Exiguobacterium H1 (H1) was isolated in this study. The changes in nitrogen metabolism functions of H1 strain were discussed in presence of disinfectants chloroxylenol (PCMX) and benzethonium chloride (BEC) alone and combined pollution (PCMX+BEC). The H1 strain could use NH4+-N, NO2--N and NO3--N as nitrogen sources and had good nitrogen removal performance under conditions of C/N ratio 25, pH 5-8, 25-35 oC and sodium acetate as carbon. PCMX and BEC alone exhibited hormesis effects on H1 strain which promoted the growth of H1 strain at low concentrations but inhibited it at high concentrations, and combined pollution showed synergistic inhibitory on H1 strain. H1 strain owned a full nitrogen metabolic pathway according to functional genes quantification. PCMX encouraged nitrification process of H1, while BEC and combined pollution mostly blocked nitrogen removal. PCMX, but not BEC, mainly led to the enrichment of resistance genes. These findings will aid in systematic assessment of contaminant tolerance characteristics of HNAD strain and its application prospects.

Study on Spline Stress of Separator Plates in a Wet Multi-Plate Clutch.

The spline teeth fracture of separator plates in wet multi-plate clutches compromises driving safety and the vehicle's lifespan. Tooth fracture is mainly caused by stress concentration at the tooth root and uneven circumferential load distribution. This paper considers parameters such as torque, teeth count, tooth profile, and misalignment errors, establishing the corresponding finite element (FE) model to analyze the impact of the above-mentioned parameters on the strength of the separator plates. Analysis under even and biased load circumstances demonstrated that an optimum tooth count and profile can significantly increase the strength of the separator plates, offering advice for the optimized design of wet multi-plate clutch separator plates.

Dual Gene Detection of H5N1 Avian Influenza Virus Based on Dual RT-RPA.

The H5N1 avian influenza virus seriously affects the health of poultry and humans. Once infected, the mortality rate is very high. Therefore, accurate and timely detection of the H5N1 avian influenza virus is beneficial for controlling its spread. This article establishes a dual gene detection method based on dual RPA for simultaneously detecting the HA and M2 genes of H5N1 avian influenza virus, for the detection of H5N1 avian influenza virus. Design specific primers for the conserved regions of the HA and M2 genes. The sensitivity of the dual RT-RPA detection method for HA and M2 genes is 1 × 10-7 ng/µL. The optimal primer ratio is 1:1, the optimal reaction temperature is 40 °C, and the optimal reaction time is 20 min. Dual RT-RPA was used to detect 72 samples, and compared with RT-qPCR detection, the Kappa value was 1 (p value < 0.05), and the clinical sample detection sensitivity and specificity were both 100%. The dual RT-RPA method is used for the first time to simultaneously detect two genes of the H5N1 avian influenza virus. As an accurate and convenient diagnostic tool, it can be used to diagnose the H5N1 avian influenza virus.

Europium Nanoparticle-Based Lateral Flow Strip Biosensors for the Detection of Quinoxaline Antibiotics and Their Main Metabolites in Fish Feeds and Tissues.

Olaquindox (OLA) and quinocetone (QCT) have been prohibited in aquatic products due to their significant toxicity and side effects. In this study, rapid and visual europium nanoparticle (EuNP)-based lateral flow strip biosensors (LFSBs) were developed for the simultaneous quantitative detection of OLA, QCT, and 3-methyl-quinoxaline-2-carboxylic acid (MQCA) in fish feed and tissue. The EuNP-LFSBs enabled sensitive detection for OLA, QCT, and MQCA with a limit of detection of 0.067, 0.017, and 0.099 ng/mL (R2 ≥ 0.9776) within 10 min. The average recovery of the EuNP-LFSBs was 95.13%, and relative standard deviations were below 9.38%. The method was verified by high-performance liquid chromatography (HPLC), and the test results were consistent. Therefore, the proposed LFSBs serve as a powerful tool to monitor quinoxalines in fish feeds and their residues in fish tissues.

Facilely tuning the coating layers of Fe nanoparticles from iron carbide to iron nitride for different performance in Fenton-like reactions.

In this study, a series of Fe-based materials are facilely synthesized using MIL-88A and melamine as precursors. Changing the mass ratio of melamine and MIL-88A could tune the coating layers of generated zero-valent iron (Fe0) particles from Fe3C to Fe3N facilely. Compared to Fe/Fe3N@NC sample, Fe/Fe3C@NC exhibits better catalytic activity and stability to degrade carbamazepine (CBZ) with peroxymonosulfate (PMS) as oxidant. Free radical quenching tests, open-circuit potential (OCP) test and electron paramagnetic resonance spectra (EPR) prove that hydroxyl radicals (OH) and superoxide radical (O2-) are dominant reactive oxygen species (ROSs) with Fe/Fe3C@NC sample. For Fe/Fe3N@NC sample, the main ROSs are changed into sulfate radicals (SO4-) and high valent iron-oxo (Fe (IV)=O) species. In addition, the better conductivity of Fe3C is beneficial for the electron transfer from Fe0 to the Fe3C, thus could keep the activity of the surface sites and obtain better stability. DFT calculation reveals the better adsorption and activation ability of Fe3C than Fe3N. Moreover, PMS can also be adsorbed on the Fe sites of Fe3N with shorter FeO bonds and longer SO bonds than on Fe3C, the Fe (IV)=O is thus present in the Fe/Fe3N@NC/PMS system. This study provides a novel strategy for the development of highly active Fe-based materials for Fenton-like reactions and thus could promote their real application.

Advances in Aptamer-Based Conjugate Recognition Techniques for the Detection of Small Molecules in Food.

Small molecules are significant risk factors for causing food safety issues, posing serious threats to human health. Sensitive screening for hazards is beneficial for enhancing public security. However, traditional detection methods are unable to meet the requirements for the field screening of small molecules. Therefore, it is necessary to develop applicable methods with high levels of sensitivity and specificity to identify the small molecules. Aptamers are short-chain nucleic acids that can specifically bind to small molecules. By utilizing aptamers to enhance the performance of recognition technology, it is possible to achieve high selectivity and sensitivity levels when detecting small molecules. There have been several varieties of aptamer target recognition techniques developed to improve the ability to detect small molecules in recent years. This review focuses on the principles of detection platforms, classifies the conjugating methods between small molecules and aptamers, summarizes advancements in aptamer-based conjugate recognition techniques for the detection of small molecules in food, and seeks to provide emerging powerful tools in the field of point-of-care diagnostics.

Phase transition-driven encapsulation of biomolecules using liquid metal with on-demand release for biomedical applications.

Robust encapsulation and controllable release of biomolecules have wide biomedical applications ranging from biosensing, drug delivery to information storage. However, conventional biomolecule encapsulation strategies have limitations in complicated operations, optical instability, and difficulty in decapsulation. Here, we report a simple, robust, and solvent-free biomolecule encapsulation strategy based on gallium liquid metal featuring low-temperature phase transition, self-healing, high hermetic sealing, and intrinsic resistance to optical damage. We sandwiched the biomolecules with the solid gallium films followed by low-temperature welding of the films for direct sealing. The gallium can not only protect DNA and enzymes from various physical and chemical damages but also allow the on-demand release of biomolecules by applying vibration to break the liquid gallium. We demonstrated that a DNA-coded image file can be recovered with up to 99.9% sequence retention after an accelerated aging test. We also showed the practical applications of the controllable release of bioreagents in a one-pot RPA-CRISPR/Cas12a reaction for SARS-COV-2 screening with a low detection limit of 10 copies within 40 min. This work may facilitate the development of robust and stimuli-responsive biomolecule capsules by using low-melting metals for biotechnology.

Development of an atmospheric pressure plasma-based OES device for in-situ mapping of Cd and related elements in plants.

We have developed an innovative optical emission spectrometry imaging device integrating a diode laser for sample introduction and an atmospheric pressure plasma based on dielectric barrier discharge for atomization and excitation. By optimizing the device parameters and ensuring appropriate leaf moisture, we achieved effective imaging with a lateral resolution as low as 50 µm. This device allows for tracking the accumulation of Cd and related species such as K, Zn, and O2+∙, in plant leaves exposed to different Cd levels and culture times. The results obtained are comparable to established in-lab imaging and quantitative methods. With its features of compact construction, minimal sample preparation, ease of operation, and low limit of detection (0.04 µg/g for Cd), this novel methodology shows promise as an in-situ elemental imaging tool for interdisciplinary applications.

A multiplex digital PCR assay for detection and quantitation of porcine circovirus type 2 and type 3.

Porcine circovirus (PCV) has become a major pathogen, causing major economic losses in the global pig industry, and PCV type 2 (PCV2) and 3 (PCV3) are distributed worldwide. We designed specific primer and probe sequences targeting PCV2 Cap and PCV3 Rap and developed a multiplex crystal digital PCR (cdPCR) method after optimizing the primer concentration, probe concentration, and annealing temperature. The multiplex cdPCR assay permits precise and differential detection of PCV2 and PCV3, with a limit of detection of 1.39 × 101 and 1.27 × 101 copies/reaction, respectively, and no cross-reaction with other porcine viruses was observed. The intra-assay and interassay coefficients of variation (CVs) were less than 8.75%, indicating good repeatability and reproducibility. To evaluate the practical value of this assay, 40 tissue samples and 70 feed samples were tested for both PCV2 and PCV3 by cdPCR and quantitative PCR (qPCR). Using multiplex cdPCR, the rates of PCV2 infection, PCV3 infection, and coinfection were 28.45%, 1.72%, and 12.93%, respectively, and using multiplex qPCR, they were 25.00%, 0.86%, and 4.31%, respectively This highly specific and sensitive multiplex cdPCR thus allows accurate simultaneous detection of PCV2 and PCV3, and it is particularly well suited for applications that require the detection of small amounts of input nucleic acid or samples with intensive processing and complex matrices.

Decoding the specificity of m6A RNA methylation and its implication in cancer therapy.

N6-methyladenosine (m6A) is the most abundant endogenous modification in eukaryotic RNAs. It plays important roles in various biological processes and diseases, including cancers. More and more studies have revealed that the deposition of m6A is specifically regulated in a context-dependent manner. Here, we review the diverse mechanisms that determine the topology of m6A along RNAs and the cell-type-specific m6A methylomes. The exon junction complex (EJC) as well as histone modifications play important roles in determining the topological distribution of m6A along nascent RNAs, while the transcription factors and RNA-binding proteins, which usually bind specific DNAs and RNAs in a cell-type-specific manner, largely account for the cell-type-specific m6A methylomes. Due to the lack of specificity of m6A writers and readers, there are still challenges to target the core m6A machinery for cancer therapies. Therefore, understanding the mechanisms underlying the specificity of m6A modifications in cancers would be important for future cancer therapies through m6A intervention.

Friction-Wear and Noise Characteristics of Friction Disks with Circular Texture.

The reduction of friction-induced noise is a crucial research area for enhancing vehicle comfort, and this paper proposes a method based on circular pit texture to achieve this goal. We conducted a long-term sliding friction test using a pin-on-disc friction and a wear test bench to verify the validity of this method. To compare the friction noise of different surfaces, texture units with varying line densities were machined on the surface of friction disk samples. The resulting friction-wear and noise characteristics of the samples were analyzed in conjunction with the microscopic morphology of the worn surfaces. The results indicate that surfaces with textures can delay the onset of squeal noise, and the pattern of its development differs from that of smooth surfaces. The noise reduction effect is most evident due to the proper distribution of textures that can form furrow-like wear marks at the wear interface. The finite element results demonstrate that this morphology can improve pressure distribution at the leading point and reduce the tendency of system instability.

LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion.

The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will inevitably develop, particularly by LTK mutations, as observed in NSCLC induced by oncogenic tyrosine kinases treated with corresponding tyrosine kinase inhibitors (TKIs). In this study, we evaluate eight LTK mutations corresponding to ALK mutations that lead to on-target resistance to lorlatinib. All LTK mutations show resistance to lorlatinib with the L650F mutation being the highest. In vitro and in vivo analyses demonstrate that gilteritinib can overcome the L650F-mediated resistance to lorlatinib. In silico analysis suggests that introduction of the L650F mutation may attenuate lorlatinib-LTK binding. Our study provides preclinical evaluations of potential on-target resistance mutations to lorlatinib, and a novel strategy to overcome the resistance.

Research Progress in Traditional Applications, Phytochemistry, Pharmacology, and Safety Evaluation of Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR) belongs to the family Cynomoriaceae. It is a perennial succulent parasitic herb with a reddish-brown coloration, predominantly submerged in sand and lacking chlorophyll. Traditionally, it has been used in ethnic medicine to treat various diseases, such as gastric ulcers, indigestion, bowel movements, and improving sexual function. To comprehensively collect CSR data, extensive literature searches were conducted using medical, ecological, and scientific databases such as Google Scholar, PubMed, Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI). This article summarizes and categorizes research on the uses, phytochemical characteristics, pharmacological activities, and toxicity of ethnic medicine, with the aim of establishing a solid foundation and proposing new avenues for exploring and developing potential applications of CSR. So far, a total of 98 compounds have been isolated and identified from CSR, including flavonoids, terpenes, steroids, and other compounds. It is worth noting that flavonoids and polysaccharides have significant antioxidant and anti-inflammatory properties. In addition, these compounds also show good application prospects in anti-tumor, antioxidant, anti-aging, anti-fatigue, anti-diabetes, and other aspects. Although extensive progress has been made in the basic research of CSR, further research is still needed to enhance the understanding of its mechanism of action and explore more unknown compounds. Our review indicates that CSR has broad prospects and deserves further research.

Injectable and Conductive Nanomicelle Hydrogel with α-Tocopherol Encapsulation for Enhanced Myocardial Infarction Repair.

Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.

Soft Robots with Plant-Inspired Gravitropism Based on Fluidic Liquid Metal.

Plants can autonomously adjust their growth direction based on the gravitropic response to maximize energy acquisition, despite lacking nerves and muscles. Endowing soft robots with gravitropism may facilitate the development of self-regulating systems free of electronics, but remains elusive. Herein, acceleration-regulated soft actuators are described that can respond to the gravitational field by leveraging the unique fluidity of liquid metal in its self-limiting oxide skin. The soft actuator is obtained by magnetic printing of the fluidic liquid metal heater circuit on a thermoresponsive liquid crystal elastomer. The Joule heat of the liquid metal circuit with gravity-regulated resistance can be programmed by changing the actuator's pose to induce the flow of liquid metal. The actuator can autonomously adjust its bending degree by the dynamic interaction between its thermomechanical response and gravity. A gravity-interactive soft gripper is also created with controllable grasping and releasing by rotating the actuator. Moreover, it is demonstrated that self-regulated oscillation motion can be achieved by interfacing the actuator with a monostable tape spring, allowing the electronics-free control of a bionic walker. This work paves the avenue for the development of liquid metal-based reconfigurable electronics and electronics-free soft robots that can perceive gravity or acceleration.

The OsWRKY72-OsAAT30/OsGSTU26 module mediates reactive oxygen species scavenging to drive heterosis for salt tolerance in hybrid rice.

Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid-parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over-parent heterosis or heterobeltiosis). Nonadditive expression and allele-specific gene expression assays showed that the glutathione S-transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt-sensitive phenotypes were associated with the OsWRKY72paternal genotype or the OsAAT30maternal genotype in core rice germplasm varieties. OsWRKY72paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72-OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice.

Integrative leaf anatomy structure, physiology, and metabolome analyses revealed the response to drought stress in sainfoin at the seedling stage.

INTRODUCTION: Sainfoin (Onobrychis viciaefolia) is a vital legume forage, and drought is the primary element impeding sainfoin growth. OBJECTIVE: The anatomical structure, physiological indexes, and metabolites of the leaves of sainfoin seedlings with a drought-resistant line of P1 (DRL) and a drought-sensitive material of 2049 (DSM) were analyzed under drought (-1.0 MPa) with polyethylene glycol-6000 (PEG-6000). METHODS: The leaf anatomy was studied by the paraffin section method. The related physiological indexes were measured by the hydroxylamine oxidation method, titanium sulfate colorimetric method, thiobarbituric acid method, acidic ninhydrin colorimetric method, and Coomassie brilliant blue method. The metabolomics analysis was composed of liquid chromatography tandem high-resolution mass spectrometry (LC-MS/MS). RESULTS: The results revealed that the thickness of the epidermis, palisade tissue, and sponge tissue of DRL were significantly greater than those of DSM. The leaves of DRL exhibited lower levels of superoxide anion (O2 •-) production rate, hydrogen peroxide (H2O2) content, and malondialdehyde (MDA) content compared with DSM, while proline (Pro) content and soluble protein (SP) content were significantly higher than those of DSM. A total of 391 differential metabolites were identified in two samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that the primary differential metabolites were concentrated into the tyrosine metabolism; isoquinoline alkaloid biosynthesis; ubiquinone and other terpenoid quinone biosynthesis; neomycin, kanamycin, and gentamicin biosynthesis; and anthocyanin biosynthesis metabolic pathways. CONCLUSION: Compared with DSM, DRL had more complete anatomical structure, lower active oxygen content, and higher antioxidant level. The results improved our insights into the drought-resistant mechanisms in sainfoin.