Search

Abstract Background To date, there is an ongoing debate regarding the ability to predict PVT development using markers of FVIII or FVIII/PC ratio. This study presents evidence-based medical findings on the influence of FVIII activity levels and FVIII/PC values in the formation of PVT in cirrhosis. Methods The search for original studies on risk factors for portal vein thrombosis (PVT) associated with cirrhosis was conducted, which primarily focused on comparing circulating FVIII activity levels or FVIII/PC ratio in cirrhotic patients with and without PVT. The quality of evidence from each study was assessed using the Newcastle-Ottawa Scale. Results The meta-analysis included a total of 10 original studies. In total, 2250 cirrhotic patients were included, with 414 having PVT and 1836 without PVT. The pooled analysis using a random-effects model showed no significant difference in standardized mean difference (SMD) for FVIII activity levels in cirrhotic patients with or without PVT (SMD = 0.12, 95% CI=-0.46 to 0.70, P = 0.68), but there was significant heterogeneity (I2 = 95.52%, P = 0.00). Meta-regression analysis indicated that differences in mean FVIII activity levels in the PVT group, the number of cases in the non-PVT group, and the study design methods partially contributed to the heterogeneity (P

C29H26ClN3O7, monoclinic, P21 (no. 4), a = 15.5488(6) Å, b = 7.9366(3) Å, c = 22.6498(9) Å, β = 93.006(2)°, V = 2,791.24(19) Å3, Z = 4, Rgt(F) = 0.0528, wRref(F2) = 0.1391, T = 292 K.

Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory disorder that is becoming the leading cause of morbidity and mortality on a global scale. There is an unmet need to investigate the underlying pathophysiological mechanisms and unlock novel therapeutic avenues for COPD. Recent research has shed light on the significant roles played by diverse noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in orchestrating the development and progression of COPD. This review provides an overview of the regulatory roles of ncRNAs in COPD, elucidating their underlying mechanisms, and illuminating the potential prospects of RNA-based therapeutics in the management of COPD.

Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycena galericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described.Mycena brunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M. albiceps and M. flosoides.

Abstract Background Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture. Methods Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed. Results Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture. Conclusions The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.

Abstract Background Due to the complexity of the metabolic pathway network of active ingredients, precise targeted synthesis of any active ingredient on a synthetic network is a huge challenge. Based on a complete analysis of the active ingredient pathway in a species, this goal can be achieved by elucidating the functional differences of each enzyme in the pathway and achieving this goal through different combinations. Lignans are a class of phytoestrogens that are present abundantly in plants and play a role in various physiological activities of plants due to their structural diversity. In addition, lignans offer various medicinal benefits to humans. Despite their value, the low concentration of lignans in plants limits their extraction and utilization. Recently, synthetic biology approaches have been explored for lignan production, but achieving the synthesis of most lignans, especially the more valuable lignan glycosides, across the entire synthetic network remains incomplete. Results By evaluating various gene construction methods and sequences, we determined that the pCDF-Duet-Prx02-PsVAO gene construction was the most effective for the production of (+)-pinoresinol, yielding up to 698.9 mg/L after shake-flask fermentation. Based on the stable production of (+)-pinoresinol, we synthesized downstream metabolites in vivo. By comparing different fermentation methods, including “one-cell, one-pot” and “multicellular one-pot”, we determined that the “multicellular one-pot” method was more effective for producing (+)-lariciresinol, (-)-secoisolariciresinol, (-)-matairesinol, and their glycoside products. The “multicellular one-pot” fermentation yielded 434.08 mg/L of (+)-lariciresinol, 96.81 mg/L of (-)-secoisolariciresinol, and 45.14 mg/L of (-)-matairesinol. Subsequently, ultilizing the strict substrate recognition pecificities of UDP-glycosyltransferase (UGT) incorporating the native uridine diphosphate glucose (UDPG) Module for in vivo synthesis of glycoside products resulted in the following yields: (+)-pinoresinol glucoside: 1.71 mg/L, (+)-lariciresinol-4-O-d-glucopyranoside: 1.3 mg/L, (+)-lariciresinol-4’-O-d-glucopyranoside: 836 µg/L, (-)-secoisolariciresinol monoglucoside: 103.77 µg/L, (-)-matairesinol-4-O-d-glucopyranoside: 86.79 µg/L, and (-)-matairesinol-4’-O-d-glucopyranoside: 74.5 µg/L. Conclusions By using various construction and fermentation methods, we successfully synthesized 10 products of the lignan pathway in Isatis indigotica Fort in Escherichia coli, with eugenol as substrate. Additionally, we obtained a diverse range of lignan products by combining different modules, setting a foundation for future high-yield lignan production.

Abstract Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Abstract Immune-related GTPase M (IRGM) induces autophagy and suppresses inflammation, but its putative role and signaling mechanism remain undefined in the pathogenesis of liver failure. This study aimed to address how IRGM attenuates inflammatory injury by regulating autophagy in liver failure. In this study, a total of 10 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and 10 healthy controls were prospectively enrolled. Intrahepatic expression of IRGM/Irgm1, NLRP3 inflammasome (NLRP3, ASC, and caspase-1), autophagy-related proteins (LC3II, P62), and inflammatory cytokines (IL-1β, TNF-α) were measured. Autophagy was activated by rapamycin (4 mg/kg) in an acute liver failure (ALF) mouse model, which was used to further study the expression of Irgm1, NLRP3 inflammasome, autophagy-related proteins, and inflammatory cytokines using both qRT-PCR and Western blot analyses. Irgm1 expression was knocked down using Irgm1 short hairpin RNA (shRNA) in lipopolysaccharide (LPS)-induced AML12 cells to investigate the effects of Irgm1 deletion on autophagy and inflammation. We found that the expression of IRGM and autophagy-related proteins was significantly downregulated while the NLRP3 inflammasome was significantly upregulated in the livers of HBV-ACLF patients and the ALF mouse model (all P

Abstract In droplet-based single-cell and single-nucleus RNA-seq assays, systematic contamination of ambient RNA molecules biases the quantification of gene expression levels. Existing methods correct the contamination for all genes globally. However, there lacks specific evaluation of correction efficacy for varying contamination levels. Here, we show that DecontX and CellBender under-correct highly contaminating genes, while SoupX and scAR over-correct lowly/non-contaminating genes. Here, we develop scCDC as the first method to detect the contamination-causing genes and only correct expression levels of these genes, some of which are cell-type markers. Compared with existing decontamination methods, scCDC excels in decontaminating highly contaminating genes while avoiding over-correction of other genes.

Abstract Currently, the biological understanding of Crohn’s disease (CD) remains limited. PANoptosis is a revolutionary form of cell death reported to participate in numerous diseases, including CD. In our study, we aimed to uncover the roles of PANoptosis in CD. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified by overlapping PANoptosis-related genes and differentially expressed genes between CD and normal samples in a combined microarray dataset. Three machine learning algorithms were adopted to detect hub DE-PRGs. To stratify the heterogeneity within CD patients, nonnegative matrix factorization clustering was conducted. In terms of immune landscape analysis, the “ssGSEA” method was applied. qRT-PCR was performed to examine the expression levels of the hub DE-PRGs in CD patients and colitis model mice. Ten hub DE-PRGs with satisfactory diagnostic performance were identified and validated: CD44, CIDEC, NDRG1, NUMA1, PEA15, RAG1, S100A8, S100A9, TIMP1 and XBP1. These genes displayed significant associations with certain immune cell types and CD-related genes. We also constructed gene‒microRNA, gene‒transcription factor and drug‒gene interaction networks. CD samples were classified into two PANoptosis patterns according to the expression levels of the hub DE-PRGs. Our results suggest that PANoptosis plays a nonnegligible role in CD by modulating the immune system and interacting with CD-related genes.

Abstract Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen–glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

An in vitro simulation of digestion and fermentation model with feces bacteria was used to explore the probiotic capacity of Polyonatum cyrtonema Hua. polysaccharide (PCP) by 16S rDNA gene sequencing and determining changes in short-chain fatty acids via GC-MS. The results showed that the digestibility of PCP was not obviously found by in vitro simulating saliva-gastrointestinal digestion model. The addition of PCP could rapidly reduce the pH of fermentation broth. PCoA analysis showed that PCP had the effect of altering gut microbiota, which was similar with inulin. At the phylum level, compared to the blank control group, the relative abundance of Firmicutes and Actinomycetes was significantly increased (P

Abstract Protein structure prediction (PSP) has been a prominent topic in bioinformatics and computational biology, aiming to predict protein function and structure from sequence data. The three‐dimensional conformation of proteins is pivotal for their intricate biological roles. With the advancement of computational capabilities and the adoption of deep learning (DL) technologies (especially Transformer network architectures), the PSP field has ushered in a brand‐new era of “neuralization.” Here, we focus on reviewing the evolution of PSP from traditional to modern deep learning‐based approaches and the characteristics of various structural prediction methods. This emphasizes the advantages of deep learning‐based hybrid prediction methods over traditional approaches. This study also provides a summary analysis of widely used bioinformatics databases and the latest structure prediction models. It discusses deep learning networks and algorithmic optimization for model training, validation, and evaluation. In addition, a summary discussion of the major advances in deep learning‐based protein structure prediction is presented. The update of AlphaFold 3 further extends the boundaries of prediction models, especially in protein‐small molecule structure prediction. This marks a key shift toward a holistic approach in biomolecular structure elucidation, aiming at solving almost all sequence‐to‐structure puzzles in various biological phenomena.

BackgroundEsketamine, the first Food and Drug Administration-approved fast-acting antidepressant, has limited use because of its addictive properties. Although the combination of dextromethorphan and bupropion partially addresses the limitations of esketamine, concerns remain regarding neurologic side effects related to dextromethorphan metabolites, and seizure risks associated with high-dose bupropion. SAL0114, a novel formulation combining deuterated dextromethorphan (in which hydrogen atoms are replaced with deuterium) with bupropion, seeks to enhance dextromethorphan stability through deuteration of its metabolic sites. This approach is expected to increase antidepressant efficacy, reduce metabolite-induced safety issues, and allow for lower bupropion dosages.MethodsRadioligand competition binding assays were used to evaluate the impact of deuterium substitution on the in vitro activity of dextromethorphan and its metabolite, dextrorphan. In vitro hepatic microsomal stability and in vivo mouse pharmacokinetic assays were performed to assess the effects of deuteration on dextromethorphan stability. Two mouse models of behavioral despair were used to determine the antidepressant and synergistic effects of deuterated dextromethorphan and bupropion. Additionally, a reserpine-induced hypothermia rat model and an ammonia-induced cough mouse model were used to assess the in vivo effects from a pathological perspective.ResultsDeuterated dextromethorphan maintained the same in vitro activity as dextromethorphan while exhibiting twice the metabolic stability both in vitro and in vivo. Combination with bupropion further improved its in vivo stability, increasing the exposure by 2.4 times. The combination demonstrated efficacy and synergistic effects in all tested animal models, showing superior efficacy compared with the dextromethorphan-bupropion combination.ConclusionDeuteration improved dextromethorphan metabolic stability without altering its in vitro activity. Bupropion enhanced this stability and synergistically boosted the antidepressant effect by increasing deuterated dextromethorphan exposure in vivo. This enhanced metabolic stability suggests a reduction in dextromethorphan metabolites associated with clinical neurological side effects. Consequently, SAL0114 is hypothesized to offer improved efficacy and safety compared with the non-deuterated combination, potentially allowing for lower bupropion dosages. Further clinical studies are required to confirm these preclinical findings.

Mesenchymal stem cells (MSCs) are naturally-derived regenerative materials that exhibit significant potential in regenerative medicine. Previous studies have demonstrated that MSCs-based therapy can improve heart function in ischemia-injured hearts, offering an exciting therapeutic intervention for myocardial ischemic infarction, a leading cause of worldwide mortality and disability. However, the efficacy of MSCs-based therapies is significantly disturbed by the myocardial microenvironment, which undergoes substantial changes following ischemic injury. After the ischemic injury, blood vessels become obstructed and damaged, and cardiomyocytes experience ischemic conditions. This activates the hypoxia-induced factor 1 (HIF-1) pathway, leading to the rapid production of several cytokines and chemokines, including vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (SDF-1), which are crucial for angiogenesis, cell migration, and tissue repair, but it is not sustainable. MSCs respond to these cytokines and chemokines by homing to the injured site and participating in myocardial regeneration. However, the deteriorated microenvironment in the injured myocardium poses challenges for cell survival, interacting with MSCs, and constraining their homing, retention, and migration capabilities, thereby limiting their regenerative potential. This review discusses how the deteriorated microenvironment negatively affects the ability of MSCs to promote myocardial regeneration. Recent studies have shown that optimizing the microenvironment through the promotion of angiogenesis can significantly enhance the efficacy of MSCs in treating myocardial infarction. This approach harnesses the full therapeutic potential of MSCs-based therapies for ischemic heart disease.

BackgroundThis investigation seeks to ascertain the efficacy of various machine learning models in forecasting early neurological deterioration (END) following thrombolysis in patients with acute ischemic stroke (AIS).MethodsEmploying data from the Shenyang Stroke Emergency Map database, this multicenter study compiled information on 7,570 AIS patients from 29 comprehensive hospitals who received thrombolytic therapy between January 2019 and December 2021. An independent testing cohort was constituted from 2,046 patients at the First People’s Hospital of Shenyang. The dataset incorporated 15 pertinent clinical and therapeutic variables. The principal outcome assessed was the occurrence of END post-thrombolysis. Model development was executed using an 80/20 split for training and internal validation, employing classifiers like logistic regression with lasso regularization (lasso regression), support vector machine (SVM), random forest (RF), gradient-boosted decision tree (GBDT), and multi-layer perceptron (MLP). The model with the highest area under the curve (AUC) was utilized to delineate feature significance.ResultsBaseline characteristics showed variability in END incidence between the training (n = 7,570; END incidence 22%) and external validation cohorts (n = 2,046; END incidence 10%; p

Bone defect repair and tumor recurrence are the main challenges in the postoperative treatment of bone tumors. The incorporation of zoledronate (ZOL) into scaffolds presents a promising approach, attributed to its osteogenic and anti-tumor properties. However, there are still some unfavorable factors that make it difficult to eradicate tumor cells at the surgical site, including drug rapid release, the insufficient anti-tumor efficacy of ZOL and the multidrug resistance of chemotherapy. Herein, a novel nano drug delivery platform mesoporous silicon-coated graphene oxide (GO/MSN) and ZOL loaded nanoparticle (GO/MSN-ZOL) were developed. Then PLLA/ GO/MSN-ZOL scaffold that integrates photothermal therapy (PTT) and chemotherapy was fabricated using poly (L-lactic acid) as raw materials by selective laser sintering (SLS) technology. The GO not only imparted scaffold with photothermal properties for localized tumor cell ablation but also significantly enhanced its anti-tumor efficacy through synergistic effects in combination with chemotherapy. The mesoporous structure and large specific surface area of MSN contribute to the sustained release of ZOL. Additionally, GO could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which in combine with ZOL’s osteoclast inhibition, enhances the bone repair capacity. This study offers a straightforward and promising strategy for treating tumor-related bone defects.

Background & aims: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. Methods: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. Results: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. Conclusion: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

BackgroundWe aimed to use lactate dehydrogenase (LDH) as a marker of inflammation burden and quantify post-stroke inflammation’s direct and indirect effect on functional disability.MethodsWe analyzed 5,129 patients with acute ischemic stroke (AIS) admitted to Shenyang First People’s Hospital. Stroke recurrence and functional outcome measured by the modified Rankin Scale (mRS) were assessed at 90 days. Functional disability was defined as mRS score > 2. Receiver operating characteristic curve and restricted cubic spline (RCS) analysis were conducted to illustrate the associations between LDH levels and 90-day functional outcomes in patients with AIS. Mediation analyses were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between LDH and functional outcome. Positive correlation between LDH and hs-CRP was found and mediation effects of stroke recurrence in the association between LDH or hs-CRP and functional disability were both less than 20%. Sensitivity analyses in different subgroups showed comparable results.ResultsAmong 5,129 included AIS patients, the median (IQR) level of LDH was 186 (161–204.4) U/L. Functional disability was seen in 1200 (23.4%) patients and recurrence was observed in 371(7.2%) patients at 90-day follow-up. Each standard deviation increase in the concentration of LDH was linked to an increased risk of functional disability (adjusted odds ratio[aOR], 1.07; 95%CI,1.04–1.09) and stroke recurrence (aOR,1.02; 95%CI, 1.01–1.04) within 90 days. The highest quartile of LDH (>204.2 U/L) had an elevated risk of suffering functional disability (aOR, 1.21; 95%CI, 1.00–1.47) and recurrence (aOR, 1.21; 95%CI,1.00–1.47) compared with the lowest quartile of LDH (

Abstract The placenta links feto‐maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex‐Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex‐Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1+ Ex‐Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex‐Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA‐seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT’s regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

Medical adhesives play an important role in clinical medicine because of their flexibility and convenient operation. However, they are still limited to laparoscopic surgeries, which have demonstrated urgent demand for liver retraction with minimal damage to the human body. Here, inspired by the suction cup structure of octopus, an adhesive patch with excellent mechanical properties, robust and switchable adhesiveness, and biocompatibility is proposed. The adhesive patch is combined by the attachment body mainly made of poly(acrylic acid) grafted with N-hydroxysuccinimide ester, crosslinked biodegradable gelatin methacrylate and biodegradable biopolymer gelatin to mimic the adhesive sucker rim, and the temperature-sensitive telescopic layer of microgel-crosslinked poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) to shrink and form internal cavity with reduced pressure. Through mechanical tests, adhesion evaluation, and biocompatibility analysis, the bioinspired adhesive patch has demonstrated its capacity not only in adhesion to tissues but also in potential treatment for medical applications, especially laparoscopic technology. The bioinspired adhesive patch can break through the limitations of traditional retraction methods, and become an ideal candidate for liver retraction in laparoscopic surgery and related clinical medicine.

Background and purpose: GLP-1 receptor agonists are clinically utilized for type 2 diabetes and obesity. In vitro and in vivo preclinical studies were performed to assess the druggability of a novel small molecule GLP-1 receptor biased agonist SAL0112. Experimental approach: The HTRF assay, FLIPR assay, TR-FRET assay, and PathHunter assay were utilized for in vitro studies. Liver transporter tests were conducted using the HEK293-OATP1B1 and HEK293-OATP1B3 cell lines. In vitro stability assessments of various species and in vivo PK studies in rodents were performed. A model of type 2 diabetes and obesity induced by a high-energy diet in transgenic C57BL/6 mice expressing the human GLP-1 receptor gene was conducted. Principal results: SAL0112 demonstrated high potency and selectivity in activating the Gαs pathway of the GLP-1 receptor, with no observed desensitization. SAL0112 demonstrated greater stability in human and rat liver microsomes compared to Danuglipron. In vivo PK studies revealed higher absorption of SAL0112 in rats. SAL0112 displayed a significantly lower potential for DDI on liver transporters compared to Danuglipron. SAL0112 led to significant reductions in body weight (P

Abstract Background Cardiovascular disease continues to be a leading cause of mortality worldwide, highlighting the need to explore innovative approaches to improve cardiovascular health outcomes. Time-restricted fasting (TRF) is a dietary intervention that involves limiting the time window for food consumption. It has gained attention for its potential benefits on metabolic health and weight management. This study aims to investigate the impact of TRF on key risk factors, including body weight, glucose metabolism, blood pressure, and lipid profile. Methods We conducted a systematic search in five databases (Scopus, Embase, PubMed, Cochrane, and Web of Science) for relevant studies up to January 2023. After applying inclusion criteria, 12 studies were eligible for analysis. Quality assessment was conducted using the ROB-2.0 tool and ROBINS-I. Risk of bias was mapped using Revman 5.3, and data analysis included Hartung-Knapp adjustment using R 4.2.2. Results The group that underwent the TRF intervention exhibited a significant decrease in body weight (SMD: -0.22; 95%CI: -0.41, -0.04; P 0.05). Conclusion TRF has shown potential as a treatment strategy for reducing total body weight by targeting adipose tissue, with potential improvements in cardiometabolic function.

Abstract Objective Long QT syndrome type 7 (Andersen–Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism. Methods and results We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs. The spontaneous pulsation rate of myocardial cells in the mutation group was significantly lower than that in the repair CRISPR group, the action potential duration was prolonged, and the Kir2.1 current of the inward rectifier potassium ion channel was decreased, which is consistent with the clinical symptoms of ATS patients. Only ZNF528, a chromatin-accessible TF related to pathogenicity, was continuously regulated beginning from the cardiac mesodermal precursor cell stage (day 4), and continued to be expressed at low levels, which was identified by WGCNA method and verified with ATAC-seq data in the mutation group. Subsequently, it indicated that seven pathways were downregulated (all p

Abstract Artemisinin is primarily synthesized and stored in the subepidermal space of the glandular trichomes of Artemisia annua. The augmentation of trichome density has been demonstrated to enhance artemisinin yield. However, existing literature lacks insights into the correlation between the stratum corneum and trichomes. This study aims to unravel the involvement of TrichomeLess Regulator 3 (TLR3), which encodes the transcription factor, in artemisinin biosynthesis and its potential association with the stratum corneum. TLR3 was identified as a candidate gene through transcriptome analysis. The role of TLR3 in trichome development and morphology was investigated using yeast two-hybrid, pull-down analysis, and RNA electrophoresis mobility assay. Our research revealed that TLR3 negatively regulates trichome development. It modulates the morphology of Arabidopsis thaliana trichomes by inhibiting branching and inducing the formation of abnormal trichomes in Artemisia annua. Overexpression of the TLR3 gene disrupts the arrangement of the stratum corneum and reduces artemisinin content. Simultaneously, TLR3 possesses the capacity to regulate stratum corneum development and trichome follicle morphology by interacting with TRICHOME AND ARTEMISININ REGULATOR 1, and CycTL. Consequently, our findings underscore the pivotal role of TLR3 in the development of glandular trichomes and stratum corneum biosynthesis, thereby influencing the morphology of Artemisia annua trichomes.

Abstract The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the industry, government, and military, DT4H is still in its early stages. This paper presents an overview of the current applications of DTs in healthcare, examines consortium research centers and their limitations, and surveys the current landscape of emerging research and development opportunities in healthcare. We envision the emergence of a collaborative global effort among stakeholders to enhance healthcare and improve the quality of life for millions of individuals worldwide through pioneering research and development in the realm of DT technology.

Abstract Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Abstract Background Identifying moral behavior in complex situations is the key ability for children to develop prosocial behavior. The theory of mind (ToM) and empathy provide the cognition and emotional motivation required for the development of moral sensitivity. In this study, we investigated the associations among ToM, empathy, and moral sensitivity and explored the possible differences between Chinese preschool children aged 4 and 5 years. Methods One hundred and thirty children completed the unexpected-content and change-of-location tasks as well as questionnaires about empathy and moral sensitivity individually. A one-way analysis of variance and the multi-group mediation SEM were used to examine the associations of the three variables and age differences. Results The scores of 5-year-old children in the dimensions of care, fairness, authority, and sanctity and the total score were higher than those of 4-year-old children. Moral sensitivity was positively correlated with both ToM and empathy after we controlled for verbal IQ and gender. Multigroup mediation analyses showed age-based differences in the associations among moral sensitivity, ToM, and empathy. Empathy’s mediation effect was partial among 4-year-old children and complete among 5-year-old children. Conclusions These findings contribute to understanding the cognitive and emotional factors in the formation of children’s moral sensitivity. They also point to a promising approach to promoting the development of moral sensitivity and evidence for educators to understand the process of children’s socialization.

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj.P0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

In this study, six types of commercially available water were selected for preparing cold brew coffee to explore the influence of water quality factors on the main components and sensory flavor of the coffee. High-performance liquid chromatography (HPLC) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used for analysis of the coffee. Physical and chemical indices, volatile and non-volatile components, and sensory evaluation were analyzed and compared, and correlations and principal component analysis (PCA) were performed. It was found that the different types of water had significantly different compositions of major ions. The contents of total phenol, chlorogenic acid, and caffeic acid, as well as antioxidant activity in the cold brew coffee were not significantly affected by the water ions, but they were significantly affected by the extraction concentration, extraction rate, pH, and titratable acid, caffeine, trigonelline, and furan volatile chemical components. The Ca2+, Mg2+, and HCO3− ions in the water were positively correlated with the extraction concentration, extraction rate, and caffeine and trigonelline concentrations in the cold brew coffee (P

Abstract Background and aims Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment. Methods Patients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence. Results Data from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p

Abstract Background To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Methods T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). Results The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P

Abstract The lattice reduction-aided algorithm has received broad attention from researchers since it operates as a maximum likelihood receiver with better system performance for multiple-input multiple-output orthogonal frequency division multiplexing systems and contains a full diversity. A novel iterative detection algorithm canceling parallel iterations that employ the lattice reduction-aided approach is proposed. Soft information is exchanged through the detector itself. Its iteration occurs inside the detector, which reduces much of the exchange cost between the multiple-input multiple-output orthogonal frequency division multiplexing detector and the turbo decoder. Since the parallel interference cancellation algorithm is constrained by the accuracy of the initial value of the detection, it is easy to form error propagation after several iterations. Due to the lattice reduction-aided algorithm, its performance is approximated with the maximum likelihood algorithm. Therefore, the lattice reduction-aided algorithm is introduced into the parallel interference cancellation algorithm to make its detection algorithm more accurate and overcome the effect of error propagation in the manuscript. Simulation results indicate that the proposed algorithm leads to an improvement of 0.8–2 dB when the bit error rate is set to 10–4 when compared to other algorithms.

Ethnopharmacological relevance: Pulsatilla decoction (PD) is a classical prescription for the treatment of ulcerative colitis. Previous studies have demonstrated that the therapeutic efficacy of PD is closely associated with the activation of Farnesoid X receptor (FXR). The activity of FXR is regulated by apical sodium-dependent bile acid transporter (ASBT), and the FXR-ASBT cascade reaction, centered around bile acid receptor FXR, plays a pivotal role in maintaining bile acid metabolic homeostasis to prevent the occurrence and progression of ulcerative colitis (UC).Aim of the study: To elucidate the underlying mechanism by which PD exerts its proteactive effects against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis, focusing on the modulation of FXR and ASBT.Materials and methods: To establish a model of acute ulcerative colitis, BALB/C mice were administered 3.5% DSS in their drinking water for consecutive 7 days. The disease activity index (DAI) was employed to evaluate the clinical symptoms exhibited by each group of mice. Goblet cell expression in colon tissue was assessed using glycogen schiff periodic acid-Schiff (PAS) and alcian blue staining techniques. Inflammatory cytokine expression in serum and colonic tissues was examined through enzyme-linked immunosorbent assay (ELISA). A PCR Array chip was utilized to screen 88 differential genes associated with the FXR-ASBT pathway in UC treatment with PD. Western blotting (WB) analysis was performed to detect protein expression levels of differentially expressed genes in mouse colon tissue.Results: The PD treatment effectively reduced the Disease Activity Index (DAI) score and mitigated colon histopathological damage, while also restoring weight and colon length. Furthermore, it significantly alleviated the severity of ulcerative colitis (UC), regulated inflammation, modulated goblet cell numbers, and restored bile acid balance. Additionally, a PCR Array analysis identified 21 differentially expressed genes involved in the FXR-ASBT pathway. Western blot results demonstrated significant restoration of FXR, GPBAR1, CYP7A1, and FGF15 protein expression levels following PD treatment; moreover, there was an observed tendency towards increased expression levels of ABCB11 and RXRα.Conclusion: The therapeutic efficacy of PD in UC mice is notable, potentially attributed to its modulation of bile acid homeostasis, enhancement of gut barrier function, and attenuation of intestinal inflammation.

In this study, Al-Si-Cu-Mg composites reinforced with Silicon carbide (SiC) particles and/or Carbon nanotubes (CNTs) were fabricated using semi-solid stirring casting technology (SSC). The aim of the study was to investigate the influence of SiC and/or CNTs on the mechanical properties, microstructural evolution, and deformation mechanisms of the Al-Si-Cu-Mg alloy. The findings indicated that the presence of SiC/CNTs in the composite had a significant effect on refining the α-Al phase and altering its grain orientation. Additionally, the results obtained from EBSD and TEM revealed that the microstructure of the Al-Si-Cu-Mg-SiC/CNTs hybrid composite (HAMC) underwent dynamic recrystallization (DRX) and static recrystallization (SRX), resulting in a fine equiaxed recrystallized structure. This process also led to the formation of high-angle grain boundaries (HAGBs) through dislocation rearrangement. The SiC particles were evenly distributed within the matrix, ensuring good interface bonding between SiC and α-Al phases. Moreover, the CNTs reacted with the matrix, resulting in the in-situ formation of the Al4C3 phase at the interface. The addition of SiC/CNTs significantly increased the tensile strength of HAMC at 25°C and 250°C, from 319MPa and 178MPa to 438MPa and 331MPa. Examination of the fracture surface of the hybrid composite unveiled that void formation occurred primarily at the regions surrounding the matrix-particle interface.

Background: The present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999–2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan–Meier method and compared by the log-rank test. Results: The nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73–0.79, p

This study aimed to investigate the effects of Lyophyllum decastes β-glucan (LDBG) in preventing high-fat diet (HFD)-induced obesity in male C57BL/6 mice, focusing on fecal gut microbiota (GM) and plasma metabolomics. LDBG treatment led to a reduction in body weight and an improvement in dyslipidemia in the HFD-fed mice. Additionally, LDBG decreased pro-inflammatory factors (TNF-α, IL-1β, and IL-6) in liver and abdominal adipose tissue and lowered lipopolysaccharide and leptin levels in plasma. LDBG also up-regulated mRNA levels of intestinal epithelial tight junction proteins, such as Occludin, Claudin-1, and zonula occludens-1 in colon tissue. Furthermore, 16S rRNA gene sequencing data suggested that LDBG reduced the relative abundance of Faecalibaculum and Ileibacterium while increasing that of Bifidobacterium and Oscillospiraceae. Untargeted metabolomics showed that LDBG significantly promoted Tryptophan metabolism, Glycerophospholipid metabolism, and the Citrate cycle, closely correlating with GM changes, particularly in Oscillospiraceae genera. This study demonstrates the potential of LDBG as a prebiotic in obesity prevention by regulating metabolite pathways.

The genus Gnaphalium (Asteraceae) is distributed across most regions of the world. Some of them are not only used as a food source, but has also been used for the treatment of various diseases including pain, rheumatism, chronic pharyngitis and arthritis in China since ancient times. In this review, we would like to summarize previous research on genus Gnaphalium, including traditional uses, phytochemistry, bioactivities and quality control. The data presented here on genus Gnaphalium was generated based on various scientific research databases, including SciFinder, PubMed, ScienceDirect, Wiley library, Web of Science, and CNKI. Analysis of these findings showed that plants in genus Gnaphalium have a capital power in various therapeutic uses, including pulmonary protection, antimicrobial activity, antioxidant activity, anti-inflammatory and anti-complementary activities, and antidiabetic effect. Consistent with this, the chemicals from the plant extracts revealed its richness in various chemicals, including flavonoids, phenolic acids, terpenoids, sterols, and others. In spite of its wide applicable value worldwide, the quality control of genus Gnaphalium is still based on local standards. Thus, we argue that a national standard is required for genus Gnaphalium in China, to validate its bioactivity and future clinical trials rigorously.

Purposes In the context of China’s “double carbon” target, energy saving and emission reduction have become one of the primary strategic objectives of current power industry. In addition to system safety, reliability, and economy, the power system also needs to introduce the “carbon emission reduction constraint” into all aspects of the system, which will present a new low carbon operation and management mode. Methods Aiming at the new power system carbon measurement and low carbon regulation and operation problems, a low carbon demand response scheduling strategy based on carbon emission flow is proposed. For the new power system, on the basis of analyzing the carbon emission influencing factors of each link of source-network-load-storage, an accurate carbon metering model based on the carbon emission flow theory is established, and a low-carbon demand response mechanism is set up with the dynamic carbon emission factor as the guiding signal to carry out optimized scheduling. Findings It is verified that the new power system source-network-load-storage coordinated optimal scheduling method based on low-carbon demand response can effectively stimulate the emission reduction potential of each link of the system, reduce carbon emissions and improve the rate of new energy consumption.

[Introduction] The rapid development of clean energy sources, such as wind and solar power, has led to significant changes in the energy structure of the power system, which consequently has increased uncertainty in safe grid operation and imposed new challenges in accurately forecasting electricity consumption. Among the numerous influencing factors on grid electricity consumption, meteorological factors exert a significant impact. Therefore, it is imperative to analyze the influence of meteorological factors on the refined forecast of grid electricity consumption. [Method] The influence of meteorological factors on electricity consumption was investigated, based on the daily electricity consumption data and meteorological elements in 2017, including the maximum temperature, average temperature, minimum temperature, atmospheric pressure, relative humidity and wind speed, and using the combined method of ensemble empirical mode decomposition (EEMD) and back-propagation (BP) neural networks. [Result] This study reveals a significant correlation between the average temperature, maximum temperature, minimum temperature, atmospheric pressure, and relative humidity with the low-frequency component of the electricity consumption series processed by EEMD, and an insignificant correlation with the high-frequency component and periodic component. [Conclusion] The electricity consumption forecast using the BP regression model exhibits considerable deviations when compared to the actual status. The electricity consumption forecast by the EEMD-BP regression model shows a significant improvement in accuracy, attributed to the incorporation of meteorological factors, indicating that the combined forecast method of EEMD-BP based on meteorological factors effectively enhances the accuracy of electricity consumption forecast. Consequently, it can serve as an effective technical support for improving short-term electricity consumption forecast methods.

In recent years, with the development of science and technology, powerful computing devices have been constantly developing. As an important foundation, deep learning (DL) technology has achieved many successes in multiple fields. In addition, the success of deep learning also relies on the support of large-scale datasets, which can provide models with a variety of images. The rich information in these images can help the model learn more about various categories of images, thereby improving the classification performance and generalization ability of the model. However, in real application scenarios, it may be difficult for most tasks to collect a large number of images or enough images for model training, which also restricts the performance of the trained model to a certain extent. Therefore, how to use limited samples to train the model with high performance becomes key. In order to improve this problem, the few-shot learning (FSL) strategy is proposed, which aims to obtain a model with strong performance through a small amount of data. Therefore, FSL can play its advantages in some real scene tasks where a large number of training data cannot be obtained. In this review, we will mainly introduce the FSL methods for image classification based on DL, which are mainly divided into four categories: methods based on data enhancement, metric learning, meta-learning and adding other tasks. First, we introduce some classic and advanced FSL methods in the order of categories. Second, we introduce some datasets that are often used to test the performance of FSL methods and the performance of some classical and advanced FSL methods on two common datasets. Finally, we discuss the current challenges and future prospects in this field.

Abstract Background Although mid-thoracic epidural analgesia benefits patients undergoing major surgery, technical difficulties often discourage its use. Improvements in technology are warranted to improve the success rate on first pass and patient comfort. The previously reported ultrasound-assisted technique using a generic needle insertion site failed to demonstrate superiority over conventional landmark techniques. A stratified needle insertion site based on sonoanatomic features may improve the technique. Methods Patients who presented for elective abdominal or thoracic surgery requesting thoracic epidural analgesia for postoperative pain control were included in this observational study. A modified ultrasound-assisted technique using a stratified needle insertion site based on ultrasound images was adopted. The number of needle passes, needle skin punctures, procedure time, overall success rate, and incidence of procedure complications were recorded. Results One hundred and twenty-eight subjects were included. The first-pass success and overall success rates were 75% (96/128) and 98% (126/128), respectively. In 95% (122/128) of patients, only one needle skin puncture was needed to access the epidural space. The median [IQR] time needed from needle insertion to access the epidural space was 59 [47–122] seconds. No complications were observed during the procedure. Conclusions This modified ultrasound-assisted mid-thoracic epidural technique has the potential to improve success rates and reduce the needling time. The data shown in our study may be a feasible basis for a prospective study comparing our ultrasound-assisted epidural placements to conventional landmark-based techniques.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (−)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (−)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.