SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Metal Clusters Confined in Chiral Zeolitic Imidazolate Framework for Circularly Polarized-Luminescence Inks.

Chiroptical activities arising in nanoclusters (NCs) are emerging as one of the most dynamic areas of modern science. However, devising an overarching strategy that is capable of concurrently enhancing the photoluminescence (PL) and circularly polarized luminescence (CPL) of metal NCs remains a formidable challenge. Herein, gold and silver nanoclusters (AuNCs, AgNCs) are endowed with CPL, for the first time, through a universal host-guest approach─centered around perturbing a chiral microenvironment within chiral hosts, simultaneously enhancing emissions. Remarkably, the photoluminescence quantum yield (PLQY) of AuNCs has undergone an increase of over 200 times upon confinement, escalating from 0.05% to 12%, and demonstrates a CPL response. Moreover, a three-dimensional (3D) model termed "NCs@CMOF" featuring CPL activity is created using metal cluster-based assembly inks through the process of 3D printing. This work introduces a potentially straightforward and versatile approach for achieving both PL enhancement and CPL activities in metal clusters.

Thiacalix[4]arene Etching of an Anisotropic Cu70H22 Intermediate for Accessing Robust Modularly Assembled Copper Nanoclusters.

Atom-precise metal nanoclusters (NCs) with large bulk (nuclearity >60) are important species for insight into the embryonic phase of metal nanoparticles and their top-down etching synthesis. Herein, we report a metastable rod-shaped 70-nuclei copper-hydride NC, [Cl@Cu70H22(PhC≡C)29(CF3COO)16]2+ (Cu70), with Cl- as the template, in which the Cl@Cu59 kernel adopts a distinctive metal packing mode along the bipolar direction, and the protective ligand shell exhibits corresponding site differentiation. In terms of metal nuclearity, Cu70 is the largest alkynyl-stabilized Cu-hydride cluster to date. As a typical highly active intermediate, Cu70 could undergo a transformation into a series of robust modularly assembled Cu clusters (B-type Cu8, A-A-type Cu22, A-B-type Cu23, and A-B-A-type Cu38) upon etching by p-tert-butylthiacalix[4]arene (H4TC4A), which could not be achieved by "one-pot" synthetic methods. Notably, the patterns of A and B blocks in the Cu NCs could be effectively modulated by employing appropriate counterions and blockers, and the modular assembly mechanism was illustrated through comprehensive solution chemistry analysis using HR-ESI-MS. Furthermore, catalytic investigations reveal that Cu38 could serve as a highly efficient catalyst for the cycloaddition of propargylic amines with CO2 under mild conditions. This work not only enriched the family of high-nuclear copper-hydride NCs but also provided new insights into the growth mechanism of metal NCs.

Pressure-Driven Switching of Photoelectron Impact Ionization-Chemical Ionization/Penning Ionization in Vacuum Ultraviolet Photoionization Mass Spectrometry.

Vacuum ultraviolet photoionization (VUV-PI) is a soft ionization technique that operates under pressures ranging from vacuum to ambient pressure. VUV-PI has played an essential role in direct sampling mass spectrometry. In this study, new ionization processes initiated by photoelectrons have been studied through the inclusion of a radio frequency (RF) electric field at different pressures. After deducting the contribution of single photoionization (SPI), the signal intensity of 1 ppmv toluene (C7H8+) in Ar was approximately 5-fold higher than that in N2. Mixed gases with different ionization energies (IEs) and excitation energies (EEs) were further investigated to reveal that metastable species were involved in the enhancement process. Reactant ions were produced by photoelectron impact ionization (PEI), which further triggered ion-molecule reactions, i.e., chemical ionization (CI). Metastable species were produced by photoelectron impact excitation (PEE), which further triggered Penning ionization (PenI). Analytes with IEs above 10.6 eV, such as CO2 (IE = 13.78 eV) and CHCl3 (IE = 11.37 eV), could be sensitively ionized by PenI with a sensitivity comparable to SPI. Except for the contribution of SPI, the dominant ionization process was switched from PEI-CI to PenI when the pressure was elevated from 50 to 500 Pa, as the electron energy gradually decreased and was only able to produce metastable states based on the kinetic energy balance equation of electrons. The conversion processes and conditions from PEI-CI to PenI will provide novel insights to develop new selective and sensitive VUV-PI sources and understand the ionization mechanism in other discharge ionization sources.

Improving the Sensitivity and Linear Range of Photoionization Ion Mobility Spectrometry via Confining the Ion Recombination and Space Charge Effects Assisted by Theoretical Modeling.

Photoionization (PI) is an efficient ionization source for ion mobility spectrometry (IMS) and mass spectrometry. Its hyphenation with IMS (PI-IMS) has been employed in various on-site analysis scenarios targeting a wide range of compounds. However, the signal intensity and linear dynamic range of PI-IMS at ambient pressure usually do not follow the Beer-Lambert law predictions, and the factors causing that negative deviation remain unclear. In this work, a variable pressure PI-IMS system was developed to examine the ion loss effects from factors like ion recombination and space charge by varying its working pressure from 1 to 0.1 bar. Assisted by theoretical modeling, it was found that ion recombination could contribute up to 90% of signal intensity loss for ambient pressure PI-IMS setups. Lowering the pressure and increasing the electric field in PI-IMS helped suppress the ion recombination process and thus an optimal pressure Poptimal appeared for best signal intensity, despite the decreased net ion number density and the increased space charge effect. A simplified theoretical equation taking ion recombination as the primary ion loss factor was derived to link Poptimal with analyte concentration and electric field in PI-IMS, enabling a swift optimization of the PI-IMS performance. For example, compared to ambient pressure, PI-IMS at a Poptimal of 0.4 bar provided a signal intensity increment of more than 400% for 0.716 ppmv toluene and also expanded the linear dynamic range by more than two times. Revealing factors influencing the PI-IMS response would also benefit the applications of other chemical ionization sources in IMS or mass spectrometry (MS).

Enhancing the Performance of Tyndall-Powell Gate Ion Mobility Spectrometry by Combining Ion Enrichment, Discrimination Reduction, and Temporal Compression into a Single Gating Process.

The broad applications of ion mobility spectrometry (IMS) demand good sensitivity and resolving power for ion species with different reduced mobilities (K0). In this work, a new Tyndall-Powell gate (TPG) gating method for combining ion enrichment, mobility discrimination reduction, and temporal compression into a single gating process is proposed to improve IMS analysis performance. The two-parallel-grid structure and well-confined gate region of the TPG make it convenient to spatiotemporally vary the electric fields within and around the gate region. Under the new gating method, a potential wave is applied on TPG grid 1 to enrich ions within the ionization region adjacent to the TPG during the gate-closed state; meanwhile, a potential wave is applied on TPG grid 2 to enhance mobility discrimination reduction and temporal compression simultaneously during the gate-open state. For triethyl phosphate (TEP) and dimethyl methylphosphonate mixtures, product ion peaks within K0 of 1.9 to 1.1 cm2/V·s exhibit a 19-fold increase in ion current compared to the traditional TPG gating method, while maintaining a resolving power of 85. The estimated limit of detection for the TEP dimer is lowered from 8 ppb to 135 ppt. The new gating method can be applied to other TPG-based IMS systems to enhance their performance in analyzing complex samples.

Soybean hypocotyl elongation is regulated by a MYB33-SWEET11/21-GA2ox8c module involving long-distance sucrose transport.

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

Artificial intelligence reveals the predictions of hematological indexes in children with acute leukemia.

Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare.

Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer.

BACKGROUND: Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients. RESULTS: To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome. CONCLUSIONS: The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

m1A regulator-mediated methylation modification patterns correlated with autophagy to predict the prognosis of hepatocellular carcinoma.

BACKGROUND: N1-methyladenosine (m1A), among the most common internal modifications on RNAs, has a crucial role to play in cancer development. The purpose of this study were systematically investigate the modification characteristics of m1A in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to m1A modification characteristics with biological functions. This model could predict the prognosis for patients with HCC. METHODS: An integrated analysis of the TCGA-LIHC database was performed to explore the gene signatures and clinical relevance of 10 m1A regulators. Furthermore, the biological pathways regulated by m1A modification patterns were investigated. The risk model was established using the genes that showed differential expression (DEGs) between various m1A modification patterns and autophagy clusters. These in vitro experiments were subsequently designed to validate the role of m1A in HCC cell growth and autophagy. Immunohistochemistry was employed to assess m1A levels and the expression of DEGs from the risk model in HCC tissues and paracancer tissues using tissue microarray. RESULTS: The risk model, constructed from five DEGs (CDK5R2, TRIM36, DCAF8L, CYP26B, and PAGE1), exhibited significant prognostic value in predicting survival rates among individuals with HCC. Moreover, HCC tissues showed decreased levels of m1A compared to paracancer tissues. Furthermore, the low m1A level group indicated a poorer clinical outcome for patients with HCC. Additionally, m1A modification may positively influence autophagy regulation, thereby inhibiting HCC cells proliferation under nutrient deficiency conditions. CONCLUSIONS: The risk model, comprising m1A regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of m1A may represent a potential target for anti-HCC strategies.

Surgical Treatment for Type A Aortic Dissection after Endovascular Aortic Repair: A 12-year, Single-Center Study.

OBJECTIVE: This study aims to investigate the clinical manifestations, operative techniques, and outcomes of patients who undergo open repair after thoracic endovascular aortic repair (TEVAR). METHODS: From January 2010 to June 2022, 113 consecutive type A aortic dissection (TAAD) patients underwent secondary open operation after TEVAR at our institution, and the median interval from primary intervention to open surgery was 12 (1.9-48.0) months. We divided the patients into two groups (RTAD (retrograde type A dissection) group, N = 56; PNAD (proximal new aortic dissection) group, N = 57) according to their anatomical features. Survival analysis during the follow-up was evaluated using a Kaplan-Meier survival curve and a log-rank test. RESULTS: The 30-day mortality was 6.2% (7/113), the median follow-up period was 31.7 (IQR 14.7-65.6) months, and the overall survival at 1 year, 5 years, and 10 years was 88.5%, 88.5%, and 87.6%, respectively. Fourteen deaths occurred during the follow-up, but there were no late aorta-related deaths. Three patients underwent total thoracoabdominal aortic replacement 1 year after a second open operation. The RTAD group had a smaller ascending aorta size (42.5 ± 7.7 mm vs 48.4 ± 11.4 mm; P < .01) and a closer proximal landing zone (P < .01) compared to the PNAD group. However, there were no differences in survival between the two groups. CONCLUSIONS: TAAD can present as an early or a late complication after TEVAR due to stent-grafting-related issues or disease progression. Open operation can be performed to treat TAAD, and this has acceptable early and mid-term outcomes. Follow-up should become mandatory for patients after TEVAR because these patients are at increased risk for TAAD.

MicroRNA-505-3p mediates cell motility of epithelial ovarian cancer via suppressing PEAK1 expression.

MicroRNAs (miRNAs) are a class of small RNA genes with important roles in cancer biology regulation. There are considerable studies regarding the roles of microRNA-505-3p (miR-505-3p) in cancer development and progression, but the function of miR-505-3p in epithelial ovarian cancer (EOC) has not been fully clarified. Comparative analysis of miRNA expression data set was used to select differentially expressed miRNAs. Quantitative real-time polymerase chain reaction was applied to detect expression levels of RNAs, while western blot and immunofluorescence staining were performed to detect expression levels of proteins of interest. The motility of EOC cells was assessed by wound healing and transwell assays. The binding and regulating relationship between miRNA and its direct target gene was investigated by dual-luciferase assay. Our results show that miR-505-3p was upregulated in recurrent EOC, which significantly inhibits EOC cell motility via modulating cell epithelial-mesenchymal transition. Furthermore, our results indicated that PEAK1 expression was inhibited by direct binding of miR-505-3p into its 3'-URT in EOC cells. Importantly, knockdown of PEAK1 attenuated the effect of mi-505-3p inhibitor on EOC cell migration and invasion. In conclusion, our findings indicate that miRNA-505-3p inhibits EOC cell motility by targeting PEAK1.

Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) Registry protocol: rationale, design and methodology.

BACKGROUND: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS. METHOD: Thirty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [5A] registry), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. DISCUSSION: The analysis of this multicenter registry will allow our better knowledge of the prognostic importance of preoperative inflammation and different anti-inflammatory strategies in adverse events after surgery for AAS. This registry is expected to provide insights into novel different inflammatory resolutions in management of AAS beyond conventional surgical repair. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04398992 (Initial Release: 05/19/2020).

Potential biomarkers of recurrent FSGS: a review.

Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria, has a high risk of progression to end-stage renal disease (ESRD). Meanwhile, the recurrence of FSGS after renal transplantation is one of the main causes of graft loss. The diagnosis of recurrent FSGS is mainly based on renal puncture biopsy transplants, an approach not widely consented by patients with early mild disease. Therefore, there is an urgent need to find definitive diagnostic markers that can act as a target for early diagnosis and intervention in the treatment of patients. In this review, we summarize the domestic and international studies on the pathophysiology, pathogenesis and earliest screening methods of FSGS and describe the functions and roles of specific circulating factors in the progression of early FSGS, in order to provide a new theoretical basis for early diagnosis of FSGS recurrence, as well as aid the exploration of therapeutic targets.

Estimating the Depths of Normal Surface Notches Using Mode-Conversion Waves at the Bottom Tip.

In this work, a two-parameter inversion problem is analyzed, related to surface crack widths for measuring depths of normal surface notches, based on a laser-based ultrasonic measurement method in the time domain. In determining the depth measurement formulas, the main technique is the time delay between reflected and scattered waves. Scattered waves are generated by two reflections along the bottom and three mode transformations at the surface of the crack tips. Moreover, the scattering angle of the mode-conversion waves is 30°. These two key factors lead to corrected item "2wß" in the depth measurement formula. A laser-based ultrasonic experimental platform is built to generate and receive surface waves in a non-contact manner on aluminum and steel specimens with surface cracks. The depth measurement method proposed in this paper has been validated through theoretical, simulation, and experimental methods. Finally, in this paper, an effective approach for quantitatively measuring crack depths, based on laser ultrasound, using the time-domain properties of surface wave propagation is provided.

Design and Fabrication of a Film Bulk Acoustic Wave Filter for 3.0 GHz-3.2 GHz S-Band.

Film bulk acoustic-wave resonators (FBARs) are widely utilized in the field of radio frequency (RF) filters due to their excellent performance, such as high operation frequency and high quality. In this paper, we present the design, fabrication, and characterization of an FBAR filter for the 3.0 GHz-3.2 GHz S-band. Using a scandium-doped aluminum nitride (Sc0.2Al0.8N) film, the filter is designed through a combined acoustic-electromagnetic simulation method, and the FBAR and filter are fabricated using an eight-step lithographic process. The measured FBAR presents an effective electromechanical coupling coefficient (keff2) value up to 13.3%, and the measured filter demonstrates a -3 dB bandwidth of 115 MHz (from 3.013 GHz to 3.128 GHz), a low insertion loss of -2.4 dB, and good out-of-band rejection of -30 dB. The measured 1 dB compression point of the fabricated filter is 30.5 dBm, and the first series resonator burns out first as the input power increases. This work paves the way for research on high-power RF filters in mobile communication.

Integrating chemical similarity and bioequivalence: an overall evaluation of the quality consistency of traditional decoction and dispensing granule decoction of Amomum villosum.

OBJECTIVE: This study aims to investigate the quality consistency between traditional decoction (TD) of Amomum villosum and its dispensing granule decoction (DGD). Fifteen batches of TD and nine batches of dispensing granules (manufactured by A, B, and C) were prepared and evaluated for their consistency. METHODS: Firstly, The chemical similarity of TD and DGD was examined using GC and HPLC, coupled with hierarchical cluster analysis (HCA), criteria importance though intercrieria correlation(CRITIC) weighting method, and principal component analysis (PCA). Secondly, the gastrointestinal motility experiments in mice, along with the CRITIC weighting method, were employed to assess the bioequivalence of TD and DGD of Amomum villosum. Finally, the entropy weight technique-gray relative analysis(GRA) method was used to compare the quality of Amomum villosum decoctions. RESULTS: ①The CRITIC weighting method indicated significantly higher scores for TD than DGD (p < 0.01). HCA and PCA results demonstrated a clear distinction between TD and DGD. ②Gastrointestinal motility test results revealed no significant difference between TD and DGD in other indicators (p > 0.05).③Gray relative analysis results showed that the relative correlation of TD was more significant than that of DGD. CONCLUSION: The chemical composition of DGD and TD differed. The biological activity of DGD-A/B was consistent with that of TD, while the difference between DGD-C and TD was significant. A comprehensive evaluation showed that TD exhibited better quality than DGD. DGD manufacturers should optimize the preparation process to enhance product quality.

The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma.

As one of the emerging hallmarks of tumorigenesis and tumor progression, metabolic remodeling is common in the tumor microenvironment. Hepatocellular carcinoma (HCC) is the third leading cause of global tumor-related mortality, causing a series of metabolic alterations in response to nutrient availability and consumption to fulfill the demands of biosynthesis and carcinogenesis. Despite the efficacy of immunotherapy in treating HCC, the response rate remains unsatisfactory. Recently, research has focused on metabolic reprogramming and its effects on the immune state of the tumor microenvironment, and immune response rate. In this review, we delineate the metabolic reprogramming observed in HCC and its influence on the tumor immune microenvironment. We discuss strategies aimed at enhancing response rates and overcoming immune resistance through metabolic interventions, focusing on targeting glucose, lipid, or amino acid metabolism, as well as systemic regulation.

The Biosynthesis Process of Small RNA and Its Pivotal Roles in Plant Development.

In the realm of plant biology, small RNAs (sRNAs) are imperative in the orchestration of gene expression, playing pivotal roles across a spectrum of developmental sequences and responses to environmental stressors. The biosynthetic cascade of sRNAs is characterized by an elaborate network of enzymatic pathways that meticulously process double-stranded RNA (dsRNA) precursors into sRNA molecules, typically 20 to 30 nucleotides in length. These sRNAs, chiefly microRNAs (miRNAs) and small interfering RNAs (siRNAs), are integral in guiding the RNA-induced silencing complex (RISC) to selectively target messenger RNAs (mRNAs) for post-transcriptional modulation. This regulation is achieved either through the targeted cleavage or the suppression of translational efficiency of the mRNAs. In plant development, sRNAs are integral to the modulation of key pathways that govern growth patterns, organ differentiation, and developmental timing. The biogenesis of sRNA itself is a fine-tuned process, beginning with transcription and proceeding through a series of processing steps involving Dicer-like enzymes and RNA-binding proteins. Recent advances in the field have illuminated the complex processes underlying the generation and function of small RNAs (sRNAs), including the identification of new sRNA categories and the clarification of their involvement in the intercommunication among diverse regulatory pathways. This review endeavors to evaluate the contemporary comprehension of sRNA biosynthesis and to underscore the pivotal role these molecules play in directing the intricate performance of plant developmental processes.