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Previous studies have shown that inquiry-based learning (IBL) and flipped learning effectively promote student engagement and learning outcomes in language classrooms. Meanwhile, technology-enhanced formative assessment (TEFA) with well-designed instructional strategies can provide engaging learning opportunities for learners of English as a Foreign Language (EFL). However, research on combining these three teaching approaches to enhance foreign language skills is scarce. Specifically, this study integrated IBL and TEFA in flipped EFL writing instruction to address the research gap. A mixed-method design was employed to explore 48 students' writing performance and their perceptions of these creative teaching strategies. The results of the quantitative analysis indicate that combining IBL and TEFA increased students' writing quality, as shown by the significant difference between their pretest and posttest writing scores. In addition, qualitative analysis of their written reflections indicated that they appreciated the dynamic and interactive learning atmosphere, displayed positive attitudes, and perceived the value of IBL and TEFA. The students also provided insights regarding the difficulties they experienced with this teaching method. The implications concerning the impact of IBL and TEFA in teaching flipped EFL writing are discussed, highlighting future suggestions for EFL educators.

Background: Vascularized composite allotransplantation (VCA) has become a viable option for restoration of devastating injuries that are not amenable to conventional reconstructive techniques. However, the relative scarcity of procedures performed worldwide, as well as the potential for iatrogenic injury with biopsies, makes studying the immunopathogenesis of acute rejection challenging. Translational VCA research focuses on developing strategies to overcome these barriers with the use of animal models can be technically challenging and difficult to replicate without highly trained microsurgeons. Methods: We describe a modified model of a femur-based composite tissue allograft using an adapted vascular cuff anastomotic technique with a tunneled skin flap in a rodent model. Results: The use of a heterotopic osteomyocutaneous flap with a subcutaneously tunneled-skin paddle to the posterolateral aspect of the recipient rodent allows for ease of flap monitoring and reduces the risk of self-mutilation. A total of six transplantations were conducted with no signs of self-mutilation. Operative time decreased as our surgical technique improved, and long-term graft tolerance was possible under our immunosuppressive regimen. Additionally, we demonstrate cases of successful transplantation in both an allogeneic and syngeneic rodent model. Conclusion: Animal models, although technically challenging, are a reliable and reproducible modality that has been used to investigate various aspects of VCA immunology. We describe the success of an osteomyocutaneous flap with a modified vascular cuff anastomosis that can be used by investigators with less experience in microsurgical techniques to further our understanding of VCA physiology. Furthermore, tunneling of the skin paddle reduces the risk of self-mutilation and other external factors affecting the graft.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system’s reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient’s reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Low-grade body inflammation is a major cause of osteoarthritis (OA), a common joint disease. Gut dysbiosis may lead to systemic inflammation which can be prevented by probiotic administration. The Lactobacillus delbrueckii subsp. lactis 557 (LDL557) has been demonstrated to have beneficial effects for anti-inflammation. This study investigated the effects of LDL557 on OA progress using monosodium iodoacetate (MIA)-induced OA of rats. Live or heat-killed (HK)-LDL557 of a low or high dose was administrated for two weeks before MIA-induced OA, and then continuously administrated for another six weeks. After taking supplements for eight weeks, OA progress was analyzed. Results showed that MIA induced knee joint swelling, chondrocyte damage, and cartilage degradation, and supplementation with a high dose of LDL557 reduced MIA-induced knee joint swelling, chondrocyte damage, and cartilage degradation. Additionally, MIA increased serum levels of the matrix-degrading enzyme MMP-13, while a high dose of HK-LDL557 decreased it for the controls. Simultaneously, bone turnover markers and inflammatory cytokines of serum were assayed, but no significant differences were found except for a TNF-α decrease from a low dose of live LDL557. These results demonstrated that supplementation with high doses of live LDL557 or HK-LDL557 can reduce the progression of MIA-induced OA in rats.

Abstract To reduce the use of antibiotics and chemicals in aquaculture, an edible herb, Bidens pilosa, has been selected as a multifunctional feed additive. Although there has been considerable research into the effects of B. pilosa on poultry, the wider effects of B. pilosa, particularly on the growth and gut microbiota of fish, remain largely unexplored. We aimed to investigate the interactive effects between the host on growth and the gut microbiota using transcriptomics and the gut microbiota in B. pilosa-fed tilapia. In this study, we added 0.5% and 1% B. pilosa to the diet and observed that the growth performance of tilapia significantly increased over 8 weeks of feeding. Comparative transcriptome analysis was performed on RNA sequence profiles obtained from liver and muscle tissues. Functional enrichment analysis revealed that B. pilosa regulates several pathways and genes involved in amino acid metabolism, lipid metabolism, carbohydrate metabolism, endocrine system, signal transduction, and metabolism of other amino acids. The expression of the selected growth-associated genes was validated by qRT–PCR. The qRT–PCR results indicated that B. pilosa may enhance growth performance by activating the expression of the liver igf1 and muscle igf1rb genes and inhibiting the expression of the muscle negative regulator mstnb. Both the enhancement of liver endocrine IGF1/IGF1Rb signaling and the suppression of muscle autocrine/paracrine MSTN signaling induced the expression of myogenic regulatory factors (MRFs), myod1, myog and mrf4 in muscle to promote muscle growth in tilapia. The predicted function of the gut microbiota showed several significantly different pathways that overlapped with the KEGG enrichment results of differentially expressed genes in the liver transcriptomes. This finding suggested that the gut microbiota may influence liver metabolism through the gut–liver axis in B. pilosa-fed tilapia. In conclusion, dietary B. pilosa can regulate endocrine IGF1 signaling and autocrine/paracrine MSTN signaling to activate the expression of MRFs to promote muscle growth and alter the composition of gut bacteria, which can then affect liver amino acid metabolism, carbohydrate metabolism, endocrine system, lipid metabolism, metabolism of other amino acids, and signal transduction in the host, ultimately enhancing growth performance. Our results suggest that B. pilosa has the potential to be a functional additive that can be used as an alternative to reduce antibiotic use as a growth promoter in aquaculture.

Abstract Background BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. Case presentation We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. Conclusions Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.

Background: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB), defined as multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone (FQ) is difficult to treat. We assessed whether the use of new or repurposed drugs (bedaquiline, delamanid, linezolid, carbapenem, clofazimine, pretomanid) mitigated treatment failure of pre-XDR-TB. Methods: MDR-TB patients managed in the Taiwan MDR-TB consortium between July 2009–December 2019 were eligible. Treatment outcomes at 30 months were assessed. Logistic regression models were constructed to investigate factors associated with treatment outcomes. Results: 109 patients with FQ-resistant MDR-TB and 218 patients with FQ-susceptible MDR-TB were included. 60 (55.1%) patients with FQ-resistant MDR-TB and 63 (28.9%) patients with FQ-susceptible MDR-TB have been treated with new or repurposed drugs (p

Abstract Diabetic nephropathy (DN) is a prototypical chronic energy metabolism imbalance disease. The AMPK/Sirt1/PGC-1α signaling pathway plays a pivotal role in regulating energy metabolism throughout the body. Gut microbiota ferment indigestible carbohydrates to produce a variety of metabolites, particularly short-chain fatty acids (SCFAs), which exert positive effects on energy metabolism. However, the potential for SCFAs to ameliorate DN-associated renal injury via the AMPK/Sirt1/PGC-1α pathway remains a matter of debate. In this study, we investigated the effects of sodium butyrate (NaB), a SCFA, on energy metabolism in mice with spontaneous DN at two different doses. Body weight, blood glucose and lipid levels, urinary protein excretion, liver and kidney function, interleukin-6 (IL-6) levels, and the expressions of AMPK, phosphorylated AMPK (p-AMPK), mitofusin 2 (MFN2), optic atrophy 1 (OPA1), and glucagon-like peptide-1 receptor (GLP-1R) were monitored in mice. Additionally, butyrate levels, gut microbiota composition, and diversity in colonic stool were also assessed. Our findings demonstrate that exogenous NaB supplementation can improve hyperglycemia and albuminuria, reduce renal tissue inflammation, inhibit extracellular matrix accumulation and glomerular hypertrophy, and could alter the gut microbiota composition in DN. Furthermore, NaB was found to upregulate the expressions of MFN2, OPA1, p-AMPK, and GLP-1R in DN renal tissue. These results suggest that NaB could improve the composition of gut microbiota in DN, activate the AMPK/Sirt1/PGC-1α signaling pathway, and enhance mitochondrial function to regulate energy metabolism throughout the body. Collectively, our findings indicate that NaB may be a novel therapeutic agent for the treatment of DN.

Abstract Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.

Summary: Background: High ulnar nerve injuries result in intrinsic muscle weakness and are inconvenient for patients. Moreover, conventional surgical techniques often fail to achieve satisfactory motor recovery. A potential reconstructive solution in the form of the supercharge end-to-side (SETS) anterior interosseous nerve (AIN) transfer method has emerged. Therefore, this study aims to compare surgical outcomes of patients with transected and in-continuity high ulnar nerve lesions following SETS AIN transfer. Methods: Between June 2015 and May 2023, patients with high ulnar palsy in the form of transection injuries or lesion-in-continuity were recruited. The assessment encompassed several objective results, including grip strength, key pinch strength, compound muscle action potential, sensory nerve action potential, and two-point discrimination tests. The muscle power of finger abduction and adduction was also recorded. Additionally, subjective questionnaires were utilized to collect data on patient-reported outcomes. Overall, the patients were followed up for up to 2 years. Results: Patients with transected high ulnar nerve lesions exhibited worse baseline performance than those with lesion-in-continuity, including motor and sensory functions. However, they experienced greater motor improvement but less sensory recovery, resulting in comparable final motor outcomes in both groups. In contrast, the transection group showed worse sensory outcomes. Conclusions: Our findings suggest that SETS AIN transfer benefits patients with high ulnar nerve palsy, regardless of the lesion type. Nonetheless, improvements may be more pronounced in patients with transected lesions.

Abstract UFMylation is a highly conserved ubiquitin-like post-translational modification that catalyzes the covalent linkage of UFM1 to its target proteins. This modification plays a critical role in the maintenance of endoplasmic reticulum proteostasis, DNA damage response, autophagy, and transcriptional regulation. Mutations in UFM1, as well as in its specific E1 enzyme UBA5 and E2 enzyme UFC1, have been genetically linked to microcephaly. Our previous research unveiled the important role of UFMylation in regulating mitosis. However, the underlying mechanisms have remained unclear due to the limited identification of substrates. In this study, we identified Eg5, a motor protein crucial for mitotic spindle assembly and maintenance, as a novel substrate for UFMylation and identified Lys564 as the crucial UFMylation site. UFMylation did not alter its transcriptional level, phosphorylation level, or protein stability, but affected the mono-ubiquitination of Eg5. During mitosis, Eg5 and UFM1 co-localize at the centrosome and spindle apparatus, and defective UFMylation leads to diminished spindle localization of Eg5. Notably, the UFMylation-defective Eg5 mutant (K564R) exhibited shorter spindles, metaphase arrest, spindle checkpoint activation, and a failure of cell division in HeLa cells. Overall, Eg5 UFMylation is essential for proper spindle organization, mitotic progression, and cell proliferation.

Abstract Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

Abstract Background The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. Methods We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. Results The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. Conclusions We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds. Graphical Abstract

Abstract In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image‐guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in‐person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post‐ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.

Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren’s syndrome dry eye disease) from non-Sjögren’s dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren’s and Sjögren’s syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren’s dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren’s syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p

Abstract Visual assessment, while the primary method for pigmentation and erythema evaluation in clinical practice, is subjective, time-consuming, and may lead to variability in observations among clinicians. Objective and quantitative techniques are required for a precise evaluation of the disease's severity and the treatment's efficacy. This research examines the precision and utility of a newly developed skin imaging system in assessing pigmentation and erythema. Sixty participants were recruited, and their facial images were analyzed with the new OBSERV 520 x skin imaging system, compared to DERMACATCH for regional analysis and VISIA for full-face examination. The degree of skin pigmentation was clinically graded using the MASI scores evaluated by dermatologists. The data revealed positive correlations between the novel skin imaging system and the two conventional instruments in quantifying pigmentation and erythema, whether in regional or full-face analysis. Furthermore, the new skin imaging system positively correlated with the clinical MASI scores (r = 0.4314, P

Abstract Multichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.

Abstract Background Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine‐to‐inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post‐transcriptional modification of genome‐encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity‐associated NAFLD and sarcopenia remains unclear. Methods ADAR2+/+/GluR‐BR/R mice (wild type [WT]) and ADAR2−/−/GluR‐BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high‐fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross‐sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. Results ADAR2 KO mice fed with HFD exhibited lower body weight (−7.7%, P

Abstract Background Intussusception, a common cause of abdominal pain in children, often lacks clear underlying causes and is mostly idiopathic. Recurrence, though rare, raises clinical concerns, with rates escalating after each episode. Factors like pathological lead points and Henoch-Schönlein purpura (HSP) are associated with recurrent cases. On the other hand, the prevalence of Helicobacter pylori (H. pylori), often asymptomatic, in children has been declining. Although its infection is reported to be linked with HSP, its role in recurrent intussusception remains unexplored. Further research is needed to understand the interplay among H. pylori (culprit pathogen), HSP (trigger), and intractable intussusception so as to develop effective management strategies. Case presentation A two-year-old girl experienced four atypical episodes of intussusception at distinct locations, which later coincided with HSP. Despite treatment with steroids, recurrent intussusception persisted, suggesting that HSP itself was not a major cause for intractable presentations. Subsequent identification of H. pylori infection and treatment with triple therapy resulted in complete resolution of her recalcitrant intussusception. Conclusion This instructive case underscored a sequence wherein H. pylori infection triggered HSP, subsequently resulting in recurrent intussusception. While H. pylori infection is not common in young children, the coexistence of intractable intussusception and steroid-resistant recurrent HSP necessitates consideration of H. pylori infection as a potential underlying pathogen.

DNA has emerged as a promising storage medium to meet the soaring need for archival data storage because of its exceptional storage density and stability. However, current DNA‐based data storage systems are incompetent of achieving high‐quality random multiplexed access and frequently accessed data storage, which impedes its practical applications. Here, a dual‐mode storage system is proposed that combines DNA‐based archival data and nanodot‐based active data. This novel data‐storage system is constructed by writing the active and archival data on the same substrate through a facile two‐step process involving scanning probe lithography (SPL), DNA synthesis, and chemical immobilization. The data files are categorized and stored orderly in different microregions of the substrate to achieve efficient random access. On each microregion, the nanodot array stores not only the concise information for the archival DNA data but also contains the corresponding primer sequence. Such interrelation between active and archival data allows for facilely data reading by efficient microscopic modalities and in situ polymerase chain reaction (PCR). Facilitated by the integration of nanodot and DNA, this novel dual‐mode storage system demonstrates efficient data access and the potential of excellent storing capacity, paving the way for the advancement of DNA‐based data storage.

Interactions between excitatory and inhibitory neurons are critical to computations in cortical circuits but their organization is difficult to assess with standard electrophysiological approaches. Within the medial entorhinal cortex, representation of location by grid and other spatial cells involves circuits in layer 2 in which excitatory stellate cells interact with each other via inhibitory parvalbumin expressing interneurons. Whether this connectivity is structured to support local circuit computations is unclear. Here, we introduce strategies to address the functional organization of excitatory-inhibitory interactions using crossed Cre- and Flp-driver mouse lines to direct targeted presynaptic optogenetic activation and postsynaptic cell identification. We then use simultaneous patch-clamp recordings from postsynaptic neurons to assess their shared input from optically activated presynaptic populations. We find that extensive axonal projections support spatially organized connectivity between stellate cells and parvalbumin interneurons, such that direct connections are often, but not always, shared by nearby neurons, whereas multisynaptic interactions coordinate inputs to neurons with greater spatial separation. We suggest that direct excitatory-inhibitory synaptic interactions may operate at the scale of grid cell clusters, with local modules defined by excitatory-inhibitory connectivity, while indirect interactions may coordinate activity at the scale of grid cell modules.

Abstract Reprogramming tumor‐associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF‐κB p65, MAPK p38 and JNK by glycolysis‐mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti‐PD‐L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

During pregnancy, the maternal body undergoes a series of adaptative physiological changes, leading to a slight increase in serum bile acid (BA) levels. Although the fetal liver can synthesize BAs since the first trimester through the alternative pathway, the BA metabolic system is immature in the fetus. Compared to adults, the fetus has a distinct composition of BA pool and limited expression of BA synthesis enzymes and transporters. Besides, the “enterohepatic circulation” of BAs is absent in fetus. Thus, fetal BAs need to be transported to the mother through the placenta for further metabolism and excretion, and maternal BAs can also be transported to the fetus. That is what we call the “fetal-placental-maternal BA circulation”. Various BA transporters and nuclear receptors are essential for maintaining the balance of this BA circulation to ensure normal fetal development. However, prenatal adverse environments can alter fetal BA metabolism, resulting in intrauterine developmental abnormalities and susceptibility to a variety of adult chronic diseases. This review summarizes the current understanding of the fetal-placental-maternal BA circulation and discusses the effects of prenatal adverse environments on this particular BA circulation, aiming to provide a theoretical basis for exploring early prevention and treatment strategies for BA metabolism-associated adverse pregnancy outcomes and long-term impairments.