A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin.

Natural product-based antiviral candidates have received significant attention. However, there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance. Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi. They have proven to be effective against a broad range of viruses by directly killing virus particles, protecting infected cells, and targeting viral antigens on their surface, among other mechanisms. As natural products, they both possess the advantage of lower toxicity, enhanced therapeutic efficacy, and even antagonistic effects against drug-resistant viral strains. Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds, demonstrating their antiviral properties. However, to date, no review on the antiviral effects of baicalein and baicalin has been published. This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms. The aim is to provide a basis for the rational development and utilization of baicalein and baicalin, as well as to promote antiviral drug research. Please cite this article as: Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024; Epub ahead of print.

Association of circulating cytokine levels and tissue-infiltrating myeloid cells with achalasia: results from Mendelian randomization and validation through clinical characteristics and single-cell RNA sequencing.

BACKGROUND: Achalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood. METHODS: We utilized Mendelian randomization (MR) to explore the causal effects of cytokine levels on achalasia, with cis-expression/protein quantitative trait loci (cis-eQTLs/pQTLs) for 47 cytokines selected from a genome-wide association study (GWAS) meta-analysis and GWAS data for achalasia obtained from FinnGen. For cytokines significantly linked to achalasia, we analyzed their plasma concentrations and expression differences in the lower esophageal sphincter (LES) using enzyme-linked immunosorbent assay and single-cell RNA sequencing (scRNA-seq) profiling, respectively. We further employed bioinformatics approaches to investigate underlying mechanisms. RESULTS: We revealed positive associations of circulating Eotaxin, macrophage inflammatory protein-1b (MIP1b), soluble E-selectin (SeSelectin) and TNF-related apoptosis-inducing ligand (TRAIL) with achalasia. When combining MR findings with scRNA-seq data, we observed upregulation of TRAIL (OR = 2.70, 95% CI, 1.20-6.07), encoded by TNFSF10, in monocytes and downregulation of interleukin-1 receptor antagonist (IL-1ra) (OR = 0.70, 95% CI 0.59-0.84), encoded by IL1RN, in FOS_macrophages in achalasia. TNFSF10high monocytes in achalasia displayed activated type I interferon signaling, and IL1RNlow FOS_macrophages exhibited increased intercellular communications with various lymphocytes, together shaping the proinflammatory microenvironment of achalasia. CONCLUSIONS: We identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10high monocytes and IL1RNlow macrophages may play a role in the pathogenesis of achalasia.

Multiple enzyme-mimic polypeptide based carbon nanoparticles by ROP and Fe coordination for ROS regulation and photo-thermal therapy against bacterial infection.

Novel strategy is urgently needed to overcome the bacterial infection all over the world due to unreasonable use of biotics. In recent years, nanozymes have attracted great interests of researchers for their high catalytic efficiency and biocompatibility. In this study, a novel multiple enzyme-mimic polypeptide-based carbon nanoparticle was synthesized by N-carboxyanhydride mediated ring opening polymerization (ROP) and Fe coordination for actualizing ROS regulation and photo-thermal therapy. The multiple enzyme-mimic activities of the nanozyme, such as peroxidase, oxidase, catalase, and glutathione peroxidase, were detailly explored in ROS regulation for potential utilization in bacterial inhibition. The photo-thermal effect of the nanozyme was investigated under 808 nm NIR irradiation. Enhanced inhibition rate of the as prepared nanozyme was observed against Gram-negative Escherichia coli (99.03 %) and Gram positive Staphylococcus aureus (99.78 %) planktonic bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) was chosen as the drug resistant bacteria model to evaluate the efficiency in bacterial biofilm disruption. Improved healing efficacy of 99.05 % against MRSA wound infection and excellent biosafety were observed in mice model experiments for the as prepared nanozyme. In conclusion, the as synthesized nanozyme with ROS regulation, enhanced bacteria inhibition, and excellent biocompatibility could be potentially applied in clinic against bacterial infection.

Progress in application of cyclic single-stranded nucleic acids.

Cyclic nucleic acids are biologically stable against nucleic acid exonucleases due to the absence of 5' and 3' termini. Studies of cyclic nucleic acids mainly focus on cyclic single-stranded nucleic acids. Cyclic single-stranded nucleic acids are further divided into circular RNA (circRNA) and circular single-stranded DNA (cssDNA). The synthesis methods of circRNA include lasso-driven cyclization, intron-paired cyclization, intron cyclization, intron complementary pairing-driven cyclization, RNA-binding protein-driven cyclization, and artificial synthesis depending on the source. Its main role is to participate in gene expression and the treatment of some diseases. Circular single-stranded DNA is mainly synthesized by chemical ligation, template-directed enzyme ligation, and new techniques for the efficient preparation of DNA single loops and topologies based on CircLigase. It is mainly used in rolling circle amplification (RCA) technology and in the bioprotection of circular aptamers and second messengers. This review focuses on the types, synthesis methods, and applications of cyclic single-stranded nucleic acids, providing a reference for further research on cyclic single-stranded nucleic acids.

Genomic, transcriptomic, and metabolomic analyses provide insights into the evolution and development of a medicinal plant Saposhnikovia divaricata (Apiaceae).

Saposhnikovia divaricata, 2n = 2x = 16, as a perennial species, is widely distributed in China, Mongolia, Russia, etc. It is a traditional Chinese herb used to treat tetanus, rubella pruritus, rheumatic arthralgia, and other diseases. Here, we assembled a 2.07 Gb and N50 scaffold length of 227.67 Mb high-quality chromosome-level genome of S. divaricata based on the PacBio Sequel II sequencing platform. The total number of genes identified was 42 948, and 42 456 of them were functionally annotated. A total of 85.07% of the genome was composed of repeat sequences, comprised mainly of long terminal repeats (LTRs) which represented 73.7% of the genome sequence. The genome size may have been affected by a recent whole-genome duplication event. Transcriptional and metabolic analyses revealed bolting and non-bolting S. divaricata differed in flavonoids, plant hormones, and some pharmacologically active components. The analysis of its genome, transcriptome, and metabolome helped to provide insights into the evolution of bolting and non-bolting phenotypes in wild and cultivated S. divaricata and lays the basis for genetic improvement of the species.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection.

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Salivary proteins NlSP5 and NlSP7 are required for optimal feeding and fitness of the brown planthopper, Nilaparvata lugens.

BACKGROUND: Saliva has a crucial role in determining the compatibility between piercing-sucking insects and their hosts. The brown planthopper (BPH) Nilaparvata lugens, a notorious pest of rice in East and Southeast Asia, secretes gelling and watery saliva when feeding on rice sap. Nlsalivap-5 (NlSP5) and Nlsalivap-7 (NlSP7) were identified as potential planthopper-specific gelling saliva components, but their biological functions remain unknown. RESULTS: Here, we showed by transcriptomic analyses that NlSP5 and NlSP7 were biasedly expressed in the salivary glands of BPHs. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome-editing system, we constructed NlSP5 and NlSP7 homozygous mutants (NlSP5-/- and NlSP7-/-). Electrical penetration graph assay showed that NlSP5-/- and NlSP7-/- mutants exhibited abnormal probing and feeding behaviors. Bioassays revealed that the loss-of-function of NlSP5 and NlSP7 significantly reduced the fitness of BPHs, with extended developmental duration, shortened lifespan, reduced weight, and impaired fecundity and hatching rates. CONCLUSION: These findings deepen our understanding of the BPH-host interaction and may provide potential targets for the management of rice planthoppers. © 2024 Society of Chemical Industry.

Antibacterial micro/nanomotors: current research progress, challenges, and opportunities.

Bacterial infections remain a formidable threat to human health, a situation exacerbated by the escalating problem of antibiotic resistance. While alternative antibacterial strategies such as oxidants, heat treatments, and metal nanoparticles (NPs) have shown potential, they come with significant drawbacks, ranging from non-specificity to potential environmental concerns. In the face of these challenges, the rapid evolution of micro/nanomotors (MNMs) stands out as a revolutionary development in the antimicrobial arena. MNMs harness various forms of energy and convert it into a substantial driving force, offering bright prospects for combating microbial threats. MNMs' mobility allows for swift and targeted interaction with bacteria, which not only improves the carrying potential of therapeutic agents but also narrows the required activation range for non-drug antimicrobial interventions like photothermal and photodynamic therapies, substantially improving their bacterial clearance rates. In this review, we summarized the diverse propulsion mechanisms of MNMs employed in antimicrobial applications and articulated their multiple functions, which include direct bactericidal action, capture and removal of microorganisms, detoxification processes, and the innovative detection of bacteria and associated toxins. Despite MNMs' potential to revolutionize antibacterial research, the translation from laboratory to clinical use remains challenging. Based on the current research status, we summarized the potential challenges and possible solutions and also prospected several key directions for future studies of MNMs for antimicrobial purposes. Collectively, by highlighting the important knowns and unknowns of antimicrobial MNMs, our present review would help to light the way forward for the field of antimicrobial MNMs and prevent unnecessary blindness and detours.

Giant magnetocaloric effect in spin supersolid candidate Na2BaCo(PO4)2.

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.

A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia.

Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.

Salvage peroral endoscopic myotomy is a promising treatment for achalasia after myotomy failure.

BACKGROUND AND AIMS: Reintervention modalities after myotomy failure in achalasia patients have yet to be established. The efficacy and safety of salvage peroral endoscopic myotomy (POEM) for treatment of achalasia after myotomy failure were evaluated in the study. METHODS: Between August 2011 and August 2021 at the Endoscopy Center of Zhongshan Hospital, 219 achalasia patients who had previously undergone a myotomy underwent a salvage POEM and were thus retrospectively enrolled in this study. After propensity score matching (PSM), operation-related parameters were compared between the salvage POEM group and the naïve POEM group. Subgroup analysis was performed between patients with previous Heller myotomy (HM) and patients with previous POEM. RESULTS: With similar baseline characteristics between both groups after PSM, the salvage POEM group presented with shorter tunnel length (11.8 ± 2.2 cm vs 12.8 ± .9 cm, P < .0001) and myotomy length (9.8 ± 2.0 cm vs 10.4 ± 1.0 cm, P < .0001) than the naïve POEM group. No significant differences were found in procedure-related adverse events between patients of salvage POEM and naïve POEM. The primary outcome of treatment success occurred in 175 of 193 patients (90.7%) in the salvage POEM group versus 362 of 374 patients (96.8%) in the naïve POEM group (P = .0046). At a 2- and 5-year follow-up, significantly higher rates of clinical failures were observed in the previous HM subgroup than in the previous POEM subgroup (P = .0433 and P = .0230, respectively). CONCLUSIONS: Salvage POEM after a previous myotomy failure, especially after a POEM failure, is a promising treatment option because it has a durable clinical relief rate.

Predicting 3D soft tissue dynamics from 2D imaging using physics informed neural networks.

Tissue dynamics play critical roles in many physiological functions and provide important metrics for clinical diagnosis. Capturing real-time high-resolution 3D images of tissue dynamics, however, remains a challenge. This study presents a hybrid physics-informed neural network algorithm that infers 3D flow-induced tissue dynamics and other physical quantities from sparse 2D images. The algorithm combines a recurrent neural network model of soft tissue with a differentiable fluid solver, leveraging prior knowledge in solid mechanics to project the governing equation on a discrete eigen space. The algorithm uses a Long-short-term memory-based recurrent encoder-decoder connected with a fully connected neural network to capture the temporal dependence of flow-structure-interaction. The effectiveness and merit of the proposed algorithm is demonstrated on synthetic data from a canine vocal fold model and experimental data from excised pigeon syringes. The results showed that the algorithm accurately reconstructs 3D vocal dynamics, aerodynamics, and acoustics from sparse 2D vibration profiles.

Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.

BACKGROUND AND AIMS: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. METHODS: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. RESULTS: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. CONCLUSION: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives.

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

A prediction model and nomogram for technical difficulty of peroral endoscopic myotomy.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a promising endoscopic technique for achalasia. We aimed to establish a regression model and develop a simple nomogram to predict the technical difficulty of POEM in a single center with large volume cases. METHODS: 3385 achalasia patients treated with POEM were included, and the technical difficulty was systemically evaluated. All of them were randomized into the training cohort (n = 1693) or internal validation cohort (n = 1692). Then, the prediction model and nomogram were proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. RESULTS: Of 3385 patients, technical difficulty happened in 417 (12.32%) cases. In the training stage, six factors were weighted based on the ß coefficient from the regression model, including age, disease duration, sigmoid esophagus, mucosal edema, submucosal fibrosis, and tunnel length. The patients were categorized into low-risk (< 0.1), medium-risk (0.1-0.25), and high-risk (> = 0.25) groups. Our score model performed satisfying discrimination with the areas under the receiver-operating characteristic curve (AUC) of 0.743 (95% confidence interval (CI), 0.701-0.785) and calibration with goodness of fit in the Hosmer-Lemeshow test (P = 0.088) in internal validation. CONCLUSIONS: The prediction model and nomogram demonstrated good performance in predicting the technical difficulty of POEM.

FoxO is required for optimal fitness of the migratory brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

The forkhead box O (FoxO) protein is the main transcriptional effector downstream of the insulin/insulin-like signaling pathway and regulates many developmental and physiological processes. Holometabolous insects with loss-of-function mutations in FoxO exhibit phenotypes distinct from those of hemimetabolous insects in which RNA interference was used. Despite the functional importance of FoxO, whether hemimetabolous insects share an evolutionally conserved function of FoxO with holometabolous insects remains to be clarified. We used the clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) genome editing-system to establish a homozygous FoxO-null mutant (NlFoxO4E ) of the wing-dimorphic brown planthopper (BPH) Nilaparvata lugens, an economically important insect pest of rice fields. The phenotypes of NlFoxO4E mutants included extended nymphal duration, shortened lifespan, reduced reproduction, and decreased stress resistance. In addition, depletion of NlFoxO promoted cell proliferation in wing buds and led to 100% long-winged morphs, in stark contrast to short-winged wild-type BPHs. These findings indicate that NlFoxO is highly functionally conserved with its counterpart in holometabolous insects, and is required for optimal fitness of N. lugens. The insights from FoxO studies may facilitate the identification of potential target genes for BPH control applications.

Orco mutagenesis causes deficiencies in olfactory sensitivity and fertility in the migratory brown planthopper, Nilaparvata lugens.

BACKGROUND: The migratory brown planthopper (BPH), Nilaparvata lugens (Hemiptera: Delphacidae), is the most destructive pest affecting rice plants in Asia and feeds exclusively on rice. Studies have investigated the olfactory response of BPHs to the major rice volatile compounds in rice. The insect olfactory co-receptor (Orco) is a crucial component of the olfactory system and is essential for odorant detection. Functional analysis of the Orco gene in BPHs would aid in the identification of their host preference. RESULTS: We identified the BPH Orco homologue (NlOrco) by Blast searching the BPH transcriptome with the Drosophila Orco gene sequence. Spatiotemporal analysis indicated that NlOrco is first expressed in the later egg stage, and is expressed mainly in the antennae in adult females. A NlOrco-knockout line (NlOrco-/- ) was generated through clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated mutagenesis. The NlOrco-/- mutants showed no response to rice volatile compounds and consequently no host-plant preference. In addition, NlOrco-/- mutants exhibited extended nymphal duration and impaired fecundity compared with wild-type BPHs. CONCLUSION: Our findings indicated that BPHs exhibit strong olfactory responses to major rice volatile compounds and suggest that NlOrco is required for the maximal fitness of BPHs. Our results may facilitate the identification of potential target genes or chemical compounds for BPH control applications. © 2022 Society of Chemical Industry.

Endoscopic submucosal dissection for gastric adenocarcinoma of the fundic gland type (chief cell predominate type): Four years' experience from a tertiary hospital.

OBJECTIVE: To summarize the endoscopic and clinicopathological features of gastric adenocarcinoma of the fundic gland type (GA-FG), and to evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of GA-FGs. METHODS: From September 2017 to August 2021, patients treated with ESD who were pathologically confirmed to have GA-FGs were included. Those with lymphovascular and distal metastasis were excluded before ESD. The medical records were retrospectively reviewed to obtain information regarding patient demographics, clinicopathological characteristics, tumor features, complete resection rate, and complications, etc. All patients underwent follow-up for at least 12 months to evaluate any local recurrence or distant metastasis. RESULTS: A total of 15 patients with an average age of 56.9 ± 10.7 years were recruited, including 11 men and 4 women. Lesions were found at the upper third (13 [86.7%]) or middle third (2 [13.3%]) of the stomach. The average lesion size was 9.1 ± 4.8 mm. Macroscopically, lesions presented as a flat elevated type with reddish or erosion on top (n = 7, 46.7%), depressed type with pale color (n = 5, 33.3%), or submucosal tumor (SMT)-like appearance type (n = 3, 20.0%). En bloc resection, complete resection and curative resection were achieved in 14 (93.3%), 13 (86.7%), and 11 (73.3%) patients, respectively. Nine (60.0%) of the lesions had submucosal invasion. One patient underwent additional surgery. No local recurrence or metastasis was detected during the follow-up duration. CONCLUSIONS: GA-FGs present with various endoscopic features. ESD appears to be effective and safe for treating early-stage GA-FGs.

The transcription factor Zfh1 acts as a wing-morph switch in planthoppers.

Insect wing polyphenism is characterized by its ability to produce two or more distinct wing morphs from a single genotype in response to changing environments. However, the molecular basis of this phenomenon remains poorly understood. Here, we identified a zinc finger homeodomain transcription factor Zfh1 that acts as an upstream regulator for the development of long-winged (LW) or shorted-winged (SW) morphs in planthoppers. Knockdown of Zfh1 directs SW-destined nymphs to develop into LW morphs by down-regulating the transcriptional level of FoxO, a prominent downstream effector of the insulin/IGF signaling (IIS) pathway. The balance between transcriptional regulation via the Zfh1-FoxO cascade and post-translational regulation via the IIS-FoxO cascade provides a flexible regulatory mechanism for the development of alternative wing morphs. These findings help us understand how phenotypic diversity is generated by altering the activity of conserved proteins, and provide an extended framework for the evolution of wing morphological diversity in insects.

Utility of endoscopic ultrasound-guided fine-needle aspiration in pancreatic cancer patients who failed to obtain a pathological diagnosis in surgical exploration.

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows for the analysis of diagnostic tissue specimens from various regions. For pancreatic tumors, especially un-resectable ones, how to obtain pathological confirmation is important for determining sub-sequent treatment. The purpose of this study is to investigate the clinical utility of EUS-FNA in patients who failed to obtain a pathological diagnosis in surgical exploration. Methods: Patients who underwent EUS-FNA due to unsuccessful biopsy in surgical exploration in our center were retrospectively reviewed. All of the patients were diagnosed with resectable disease before surgery but were found to be unresectable during surgery. The positive rate of pathological diagnosis of EUS-FNA was analyzed. Results: A total of 11 patients were included in this study, among which 8 were males and 3 were females. The median age of the patients was 55 years (range, 48 to 73 years). The median lesion size was 34 mm (range, 25 to 44 mm). The median number of needle passes was 3 (range, 1 to 3). Two patients underwent biliary stent implantation while 3 patients underwent gastrojejunostomy before EUS-FNA. The technical success rate of EUS-FNA was 100% (11/11); 10 (90.9%, 10/11) samples were positive and 1 was negative (being inadequate). Conclusions: Intraoperative biopsy is the first choice diagnostic modality for unresectable pancreatic neoplasms. However, for patients who fail to obtain a pathological diagnosis in surgical exploration, EUS-FNA is still worth an attempt.