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Abstract Background A comprehensive understanding of the clinical characteristics and prognostic factors associated with axial chondroblastoma (ACB) is still lacking. This study aimed to understand the clinical characteristics and prognostic factors of axial chondroblastoma (ACB) and compare them with extra-axial chondroblastoma (EACB). Methods A retrospective review of our institution’s local database was conducted, encompassing a total of 132 CB patients, of which 61 were diagnosed with ACB and 71 with EACB. Immunohistochemistry was employed to evaluate the expression levels of vimentin, S100, and cytokeratin. Results ACB and EACB shared similar characteristics, with the exception of advanced age, tumor size, elevated Vim expression, incidence of surrounding tissue invasion, and postoperative sensory or motor dysfunction. While wide resection and absence of surrounding tissue invasion consistently showed a favorable association with survival in both ACB and EACB cohorts during univariate analysis, most parameters exhibited differential prognostic significance between the two groups. Notably, the significant prognostic factors for local recurrence-free survival in the ACB cohort included the type of resection and the presence of chicken-wire calcification. In the multivariate analysis of overall survival, the type of resection emerged as a significant predictor in the ACB cohort, whereas in the EACB group, the type of resection and the occurrence of postoperative sensory or motor dysfunction were predictive of overall survival. Conclusion There may exist distinct biological behaviors between ACB and EACB, thereby providing valuable insights into the prognostic characteristics of ACB patients and contributing to enhanced outcome prediction in this particular patient population.

Abstract Background Sandhoff disease (SD) is a rare neurological disease with high clinical heterogeneity. SD in juvenile form is much rarer and it is often misdiagnosed in clinics. Therein, it is necessary to provide more cases and review the literature on juvenile onset SD. Case presentation A 14 years-old boy with eight years of walking difficulties, and was ever misdiagnosed as spinocerebellar ataxia. We found this patient after genetic testing carried rs201580118 and a novel gross deletion in HEXB (g.74012742_74052694del). Through review the literature, we found that was the first gross deletion identified at the 3’end of HEXB, associated with juvenile onset SD from China. Conclusion This case expanded our knowledge about the genotype and phenotype correlations in SD. Comprehensive genetic testing is important for the diagnosis of unexplained ataxia.

Ventricular septal rupture (VSR) is a catastrophic mechanical complication of acute myocardial infarction (AMI) that can result in acute heart failure. Delaying operative intervention frequently leads to cardiogenic shock and multi-organ failure. Here we report a case of massive anterior MI complicated with VSR that was discovered through cardiac Doppler ultrasound and suspected multiple organ hemorrhage. The patient showed signs of rapid cardiogenic shock and eventually died. The morphological changes of VSR and MI were identified during necropsy, and microscopic examinations of the heart, brain, and kidney revealed multiple organ hemorrhage. This autopsy case suggested that the complication of VSR caused by AMI results in a reduction of oxygen and nutrient content of the circulating blood throughout the body and, eventually, functional failure of multiple organs. We provide clinical and pathological evidence elucidating changes in multiple organs under the severe condition of post-infarction VSR and demonstrate the consequences of a lack of immediate surgery and sufficient medical intervention for a patient suffering from AMI with VSR.

Diphtheria toxin A (DTA) is an exotoxin secreted by Corynebacterium diphtheriae. After entering the cell through receptor-mediated manner, DTA can trigger the programmed cell death mechanism and lead to cell death. In 2001, Michiko Saito established a Diphtheria toxin receptor–mediated cell knockout system, which can conditional deplete specific cell type in transgenic mice. This system is not only very useful in the pathogenesis study of human diseases, but also has a wide application prospect in the study of organ development and regeneration. In 2008, David Voehringer described a newly generated mouse strain that encodes DTA under control of a loxP-flanked stop cassette in the ubiquitously expressed ROSA26 locus. Thereby, it can be used in combination with tissue-specific and/or inducible Cre-expressing mouse strains to achieve toxin-mediated cell ablation in vivo. The application of DTA–mediated cell knockout system in mice has been widely reported, but it has rarely been used in human cells. Accordingly, we generated a human embryonic stem cell line (SMUDHe010-A-1B) carrying inducible DTA expression cassette (loxp-stop-loxp-DTA, LSL-DTA) using CRISPR/Cas9-mediated homologous recombination. The cell line preserves normal karyotype, pluripotency and the ability to differentiate into all three germ layers. Moreover, the cell line can be used to prepare human organoid, which may provide a model for achieving conditional cell ablation in human tissues and organs.

BackgroundProteases secreted by Trichinella spiralis intestinal infective larvae (IIL) play an important role in larval invasion and pathogenesis. However, the mechanism through which proteases mediate larval invasion of intestinal epithelial cells (IECs) remains unclear. A novel T. spiralis trypsin (TsTryp) was identified in IIL excretory/secretory (ES) proteins. It was an early and highly expressed protease at IIL stage, and had the potential as an early diagnostic antigen. The aim of this study was to investigate the biological characteristics of this novel TsTryp, its role in larval invasion of gut epithelium, and the mechanisms involved.Methodology/principal findingTsTryp with C-terminal domain was cloned and expressed in Escherichia coli BL21 (DE3), and the rTsTryp had the enzymatic activity of natural trypsin, but it could not directly degrade gut tight junctions (TJs) proteins. qPCR and western blotting showed that TsTryp was highly expressed at the invasive IIL stage. Immunofluorescence assay (IFA), ELISA and Far Western blotting revealed that rTsTryp specifically bound to IECs, and confocal microscopy showed that the binding of rTsTryp with IECs was mainly localized in the cytomembrane. Co-immunoprecipitation (Co-IP) confirmed that rTsTryp bound to protease activated receptors 2 (PAR2) in Caco-2 cells. rTsTryp binding to PAR2 resulted in decreased expression levels of ZO-1 and occludin and increased paracellular permeability in Caco-2 monolayers by activating the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. rTsTryp decreased TJs expression and increased epithelial permeability, which could be abrogated by the PAR2 antagonist AZ3451 and ERK1/2 inhibitor PD98059. rTsTryp facilitated larval invasion of IECs, and anti-rTsTryp antibodies inhibited invasion. Both inhibitors impeded larval invasion and alleviated intestinal inflammation in vitro and in vivo.ConclusionsTsTryp binding to PAR2 activated the ERK1/2 pathway, decreased the expression of gut TJs proteins, disrupted epithelial integrity and barrier function, and consequently mediated larval invasion of the gut mucosa. Therefore, rTsTryp could be regarded as a potential vaccine target for blocking T. spiralis invasion and infection.

ARHGEF17 encodes the protein RhoGEF17, which is highly expressed in vascular endothelial cells. It is a guanine nucleotide exchange factor (GEF) that accelerates the exchange of GDP with GTP on many small GTPases through its Dbl homology (DH) domain, enabling the activation of Rho-GTPases such as RhoA, RhoB, and RhoC. Rho GTPase-regulated changes in the actin cytoskeleton and cell adhesion kinetics are the main mechanisms mediating many endothelial cell (EC) alterations, including cell morphology, migration, and division changes, which profoundly affect EC barrier function. This review focuses on ARHGEF17 expression, activation and biological functions in ECs, linking its regulation of cellular morphology, migration, mitosis and other cellular behaviors to disease onset and progression. Understanding ARHGEF17 mechanisms of action will contribute to the design of therapeutic approaches targeting RhoGEF17, a potential drug target for the treatment of various endothelium-related diseases, Such as vascular inflammation, carcinogenesis and transendothelial metastasis of tumors.

Epilepsy is a group of enduring neurological disorder characterized by spontaneous and recurrent seizures with heterogeneous etiology, clinical expression, severity, and prognosis. Growing body of research investigates that epileptic seizures are originated from neuronal synchronized and excessive electrical activity. However, the underlying molecular mechanisms of epileptogenesis have not yet been fully elucidated and 30% of epileptic patients still are resistant to the currently available pharmacological treatments with recurrent seizures throughout life. Over the past two decades years accumulated evidences provide strong support to the hypothesis that neuroinflammation, including microglia and astrocytes activation, a cascade of inflammatory mediator releasing, and peripheral immune cells infiltration from blood into brain, is associated with epileptogenesis. Meanwhile, an increasing body of preclinical researches reveal that the anti-inflammatory therapeutics targeting crucial inflammatory components are effective and promising in the treatment of epilepsy. The aim of the present study is to highlight the current understanding of the potential neuroinflammatory mechanisms in epileptogenesis and the potential therapeutic targets against epileptic seizures.

Abstract Background Premature infants are inevitably exposed to painful events, including repetitive procedures, inflammation, or mixed stimulation that may induce long‐term behavioral outcomes. Here, we set up three neonatal painful models to investigate their long‐term effect on somatosensation and cognition. Methods Three types of neonatal pain models in rat were set up. Rat pups were randomly assigned to four groups. The needling pain (NP) group received repetitive needle pricks on the paws from the day of birth (PD0) to postnatal day 7 (PD7) to mimic the diagnostic and therapeutic procedures. The inflammatory pain (IP) group received the injection of carrageenan into the left hindpaw at PD3 to induce IP in peripheral tissues. The mixed pain group received a combination of the NP and IP (NIP). The control (CON) group was untreated. We performed behavioral and biochemical testing of juvenile rats (PD21–PD26). Results The NIP group showed a longer hypersensitivity than the NP group, when given a secondary inflammatory stimulation. NP led to insensitivity to anxiety‐causing stimuli and impairment of fear memory both aggravated by NIP. NP reduced the expression of synapse‐related molecules (GluN1/PSD95/GFAP) in the medial prefrontal cortex, and NIP exacerbated this decrease. The corticosterone secretion in the NIP group increased after the behavioral task, compared with those in other three groups. Conclusion A combination of NP with inflammation occurring in the neonatal period might aggravate the adverse effects of each on somatosensory and cognitive development of rats, the mechanism of which might be associated with the increase of corticosterone secretion and the dysregulation of synaptic molecules.

This study aimed to investigate the atomization mechanism of a flashing jet (FJ), focusing on the potential factors that influence the atomization performance of the device. Those factors include surfactant, electrolyte, and drug concentration. In this work, Tween 80, sodium chloride (NaCl), and salbutamol sulfate (SBS) were used for the study. The aerosol's mass median aerodynamic diameter (MMAD) was investigated for analysis. The drug delivery ability of the FJ prototype was compared with the Pari nebulizer. Our data suggested that the MMAD of aerosol decreased as the concentration of Tween 80 increased, but the critical micelle concentration point was not influenced. Upon adding NaCl to pure water, with the increase of NaCl concentration, the MMAD of aerosol initially decreased significantly and then increased, reaching the lowest point when 0.05% NaCl was used. A higher concentration of SBS was beneficial for the atomization performance. When the SBS concentration was 5 mg/mL, the MMAD values of the FJ prototype and Pari nebulizer were 2.28 ± 0.15 and 1.03 ± 0.21 μm, respectively, and the fine particle dose (%TDD) of the FJ prototype and Pari nebulizer was 50.99 ± 5.88 and 53.51 ± 4.58%, respectively. Interestingly, the concentration of SBS has no effect on the residual dosage level of the FJ prototype, indicating that it can be applied in atomizing high-concentration solutions. In summary, surfactant, electrolyte, and drug concentration played an important role in the atomization performance of the FJ prototype and these ingredients are also crucial factors that should be considered in future formulation studies.

The brown planthopper (Nilaparvata lugens) is the main migratory pest in many rice growing areas in Asia. E78 is a member of the nuclear hormone receptor superfamily which plays an important role in egg development and maternal regulation of early embryogenesis. In this study, brown planthopper E78 (NlE78) was cloned, and the predicted amino acid sequence showed that it contains two conserved domains: NR-LBD and DBD. qRT-PCR showed that the expression of NlE78 is high in the fifth instar nymphs and the ovaries of females. After downregulation of NlE78, the rate of moulting failure (33.2%) increased significantly, and ovarian development was delayed. However, when NlE78 was downregulated together with NlE93, the emergence rate increased significantly (78.79%), and ovarian development was similar to that when NlE78 was downregulated but not delayed. A co-immunoprecipitation experiment showed that NlE78 interacts with NlE93, a crucial downstream transcription factor of the ecdysone signalling pathway. Cellular localization by immunofluorescence revealed that NlE78 and NlE93 are expressed in the nucleus. This study indicates that NlE78 regulates ovarian development and moulting, possibly through its interaction with NlE93. This study is of great significance for the development of new pesticides and control methods based on newly discovered targets.

Abstract Background Guillain–Barre syndrome after myocardial infarction occurs infrequently, and its occurrence following percutaneous coronary intervention is extremely rare. Due to the high mortality rate of myocardial infarction and the disability of Guillain–Barre syndrome, early identification of Guillain–Barre syndrome after myocardial infarction and early intervention can decrease the mortality rate, lead to early recovery, and provide a better outcome. Case presentation Herein, we reported a rare case of Guillain–Barre syndrome after myocardial infarction treated with percutaneous coronary intervention. The patient was a 75-year-old woman from China who was admitted to hospital due to sudden loss of consciousness. Electrocardiography showed acute myocardial infarction in the right ventricle and inferior and posterior walls. The patient underwent emergency percutaneous intervention of the posterior collateral artery of the right coronary artery. Soon after, her condition worsened resulting in limb weakness and numbness. Unfortunately, she continued to develop respiratory failure, and treated with intravenous immunoglobulin and ventilator-assisted breathing. A physical examination showed hypotonia of all four limbs, complete quadriplegia, bulbar palsy, dysarthria, and tendon areflexia. Serum immunoglobulin (Ig) G anti-ganglioside antibody analysis was positive with anti-GT1a antibodies (+ +), anti-GM1 antibodies ( +), anti-GM2 antibodies ( +), and anti-GM4 antibodies ( +), and he was diagnosed with Guillain–Barre syndrome after myocardial infarction. She was discharged due to poor response to treatment. The patient died two days after being discharged. Conclusions Myocardial infarction and/or percutaneous coronary intervention may activate immune-mediated response and cause severe complications. Clinician should be alert to Guillain–Barre syndrome after myocardial infarction and/or percutaneous coronary intervention.

Abstract Background Accurately classifying complex diseases is crucial for diagnosis and personalized treatment. Integrating multi-omics data has been demonstrated to enhance the accuracy of analyzing and classifying complex diseases. This can be attributed to the highly correlated nature of the data with various diseases, as well as the comprehensive and complementary information it provides. However, integrating multi-omics data for complex diseases is challenged by data characteristics such as high imbalance, scale variation, heterogeneity, and noise interference. These challenges further emphasize the importance of developing effective methods for multi-omics data integration. Results We proposed a novel multi-omics data learning model called MODILM, which integrates multiple omics data to improve the classification accuracy of complex diseases by obtaining more significant and complementary information from different single-omics data. Our approach includes four key steps: 1) constructing a similarity network for each omics data using the cosine similarity measure, 2) leveraging Graph Attention Networks to learn sample-specific and intra-association features from similarity networks for single-omics data, 3) using Multilayer Perceptron networks to map learned features to a new feature space, thereby strengthening and extracting high-level omics-specific features, and 4) fusing these high-level features using a View Correlation Discovery Network to learn cross-omics features in the label space, which results in unique class-level distinctiveness for complex diseases. To demonstrate the effectiveness of MODILM, we conducted experiments on six benchmark datasets consisting of miRNA expression, mRNA, and DNA methylation data. Our results show that MODILM outperforms state-of-the-art methods, effectively improving the accuracy of complex disease classification. Conclusions Our MODILM provides a more competitive way to extract and integrate important and complementary information from multiple omics data, providing a very promising tool for supporting decision-making for clinical diagnosis.

The international standards IEEE 1474 and IEC 62290 for fully automatic operation (FAO) systems in urban rail transit were respectively set by IEEE-SA (institute of electrical and electronics engineers-standard association) and IEC (international electrotechnical commission) in 1999 and 2004. These two standards are different but related. In this paper, the working progress, relevance, the driverless definition, application scope, architecture, functional requirements and focus issues of IEC 62290 and IEEE 1474 are compared and analyzed respectively. IEEE 1474 is the theoretical foundation for research and development personnel in the field of railway signaling, which is applicable to operation control systems of urban rail transit, trunk railways and medium to high speed maglev, and IEC 62290 is more suitable for FAO systems in urban rail transit.

We report a case of lupus erythematosus panniculitis misdiagnosed as vasculitis. A 7-year-old boy presented with a 2-year history of erythema and ulceration on the left lower abdomen and depressed skin on the left buttock. He had been diagnosed with vasculitis and skin infection in other hospitals for many times. Dermatological examination showed scattered dark erythema on the left lower abdomen, green bean to nail sized necrosis and ulcers with adhesive black crusts on some areas, and several porcelain-white mild atrophic scars. Non-atrophic band-like depression in normal color was observed on the left hip, ilium, left lower abdomen and the left groin. The skin could be pinched. Histopathological changes in the skin lesions included liquefaction degeneration of basal cells, pigment incontinence, infiltration of lymphocytes and plasma cells around dermal vessels and appendages, mucin deposition between collagen bundles, adipose atrophy, encapsulation of fatty lobules, and positive for Alcian blue staining. The final diagnosis was lupus erythematosus panniculitis. The patient was treated with oral hydroxychloroquine 0.1 g/qd and methylprednisolone 16 mg/qd, and topical mucopolysaccharide polysulfate cream, centella triterpenes cream and crisaborole ointment. Ulcers were healed without new lesion and erythema at one-year follow-up.

Abstract Objective This study aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) for infertility and recurrent spontaneous abortion. Methods Existing research was searched in PubMed, Embase and Cochrane Library till Dec 2021. Randomized control trials (RCTs) that compared G-CSF administration with the control group in infertility women undergoing IVF were included. The primary outcomes included clinical pregnancy rate; the secondary outcomes included live birth rate, abortion ratebiochemical pregnancy rate, embryo implantation rate, as well as endometrial thickness. Result(s) 20 RCTs were included in this study. G-CSF increased the clinical pregnancy rate (RR = 1.85; 95% CI: 1.07, 3.18) and the endometrial thickness (MD = 2.25; 95% CI: 1.58,2.92;) in patients with thin endometrium undergoing IVF. G-CSF increased the biochemical pregnancy rate (RR = 2.12; 95% CI: 1.54, 2.93), the embryo implantation rate (RR = 2.51; 95% CI: 1.82, 3.47) and the clinical pregnancy rate (RR = 1.93; 95% CI: 1.63, 2.29) in patients with a history of repeated implantation failure undergoing IVF. No differences were found in pregnancy outcomes of general IVF patients. Conclusions Granulocyte colony-stimulating factor is likely to be a potential option for infertility women undergoing IVF with thin endometrium or recurrent implantation failure . Trial registration Retrospectively registered (The PROSPERO registration number: CRD42022360161).

Surfactin, a cyclic lipopeptide produced by microbes belonging to the genus Bacillus, is one of the most effective biosurfactants available in many industrial fields. However, its low production and high cost have intensively constrained its commercial applications. In this review, we first summarize the molecular structure, biological properties, beneficial roles and potential applications of surfactin in the fields of medical care and food safety, highlighting the great medical and commercial values of making its industrial production into reality. Further, genetic regulation for surfactin biosynthesis and advanced strategies for enhancing its microbial production, including optimizing fermentation conditions, rational genetic engineering and synthetic biology combined with metabolic engineering approaches, are elucidated. Finally, prospects for improving surfactin biosynthesis are discussed, and the establishment of suitable chassis hosts for exogenous production of surfactin might serve as an important strategy in future research.

Plastic sports-fields are commonly used in communities, schools and other public places nowadays, which can offer positive benefits to fitness and sports. Plastic sports-fields are usually made of petroleum-based materials. Under high-temperature weather, various potentially harmful volatile organic compounds (VOCs) can be released to the ambient air, which pose a potential health risk to people who are on the plastic sports-field or living near the plastic sports-field. In our previous work, an analytical tool for onsite investigation of air pollutants was developed by drone-based solid-phase microextraction (drone-SPME) coupled with portable gas chromatographymass spectrometry (PGC-MS). In this work, the drome-SPME-PGC-MS method was further used to analyze the air pollutants in the plastic sports-field. The volatile air pollutants such as benzothiazole and benzene were identified by NIST standard spectra and standard substances. The results showed that benzothiazole was released from the ground material of plastic sports-fields, while benzene was mainly released from the paint that was painted at the fence of plastic sports-fields. Analytical performances, such as sensitivity, reproducibility, and quantitation were investigated using drone-SPME-PGC-MS. The relative standard deviations (RSDs) of benzene (1.0 μg/L) and benzothiazole (1.0 μg/L) were 13.2% and 11.4% (n=6), respectively, indicating the high reliability of drone-SPME for air sampling. The limits of detection (LODs) of benzene and benzothiazole were 0.036 μg/L and 0.088 μg/L (S/N=3), respectively, showing good sensitivity for air analysis. The different concentrations of benzene and benzothiazole in a glass container were detected using this method, showing good linear responses (benzene: 0.044-2.20 μg/L, R2=0.992 9; benzothiazoles: 0.10-2.10 μg/L, R2=0.993 7). Moreover, benzene and benzothiazole in the air at different plastic sportsfields were quantitative detected by established drone-SPME-PGC-MS. Furthermore, the releases and distributions of benzothiazole and benzene at different temperatures (33, 12 ℃) and different heights (0.5-40 m) were investigated, showing that these air pollutants were mainly distributed at the ground layer (≤ 5 m) and were mainly released at high-temperature conditions (33 ℃). Overall, the drone-SPME-PGC-MS is a promising analytical method for the onsite investigation of air pollutants at the plastic sports-fields.

Abstract The risk of cardiovascular disease (CVD) is a serious health threat to human society worldwide. The use of machine learning methods to predict the risk of CVD is of great relevance to identify high-risk patients and take timely interventions. In this study, we propose the XGBH machine learning model, which is a CVD risk prediction model based on key contributing features. In this paper, the generalisation of the model was enhanced by adding retrospective data of 14,832 Chinese Shanxi CVD patients to the kaggle dataset. The XGBH risk prediction model proposed in this paper was validated to be highly accurate (AUC = 0.81) compared to the baseline risk score (AUC = 0.65), and the accuracy of the model for CVD risk prediction was improved with the inclusion of the conventional biometric BMI variable. To increase the clinical application of the model, a simpler diagnostic model was designed in this paper, which requires only three characteristics from the patient (age, value of systolic blood pressure and whether cholesterol is normal or not) to enable early intervention in the treatment of high-risk patients with a slight reduction in accuracy (AUC = 0.79). Ultimately, a CVD risk score model with few features and high accuracy will be established based on the main contributing features. Of course, further prospective studies, as well as studies with other populations, are needed to assess the actual clinical effectiveness of the XGBH risk prediction model.

Abstract Background and objective Whether obstructive sleep apnea (OSA) is associated with worse prognosis in patients with acute coronary syndrome (ACS) with or without prior stroke remains unclear. We investigated the association of OSA with cardiovascular events in ACS patients with or without prior stroke. Methods Between June 2015 and January 2020, we prospectively recruited eligible ACS patients who underwent cardiorespiratory polygraphy during hospitalization. We defined OSA as an apnea hypopnea index (AHI) ≥ 15 events/hour. The primary composite end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Results Among 1927 patients enrolled, 207 patients had prior stroke (10.7%) and 1014 had OSA (52.6%). After a mean follow-up of 2.9 years, patients with stroke had significantly higher risk of MACCEs than those without stroke (hazard ratio [HR]:1.49; 95% confidence interval [CI]: 1.12–1.98, P = 0.007). The multivariate analysis showed that patients with OSA had 2.0 times the risk of MACCEs in prior stroke group (41 events [33.9%] vs 18 events [20.9%]; HR:2.04, 95% CI:1.13–3.69, P = 0.018), but not in non-prior stroke group (186 events [20.8%] vs 144 events [17.4]; HR:1.21, 95% CI 0.96–1.52, P = 0.10). No significant interaction was noted between prior stroke and OSA for MACCE (interaction P = 0.17). Conclusions Among ACS patients, the presence of OSA was associated with an increased risk of cardiovascular events in patients with prior stroke. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS and prior stroke are warranted. Trial registration Clinicaltrials.gov identifier NCT03362385.

Abstract Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P

Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by in vivo and in vitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15 weeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development.

Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to “see” light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called “photoneuroendocrinology”, which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light’s beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin’s photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin’s unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.

From 2001 to 2020, three typhoons with similar moving paths and intensities were found to trigger markedly different cooling off northeastern Taiwan. They were typhoons Utor (2001), Nuri (2008), and Hagupit (2008), which led to maximum sea surface temperature (SST) cooling temperatures of 8.8, 2.7, and 1.4 °C, respectively. The drastic cooling discrepancy implies that the existing understanding of the key mechanism leading to the cooling off northeastern Taiwan could be insufficient. For further exploring the key reason(s) contributing to the marked discrepancy, a regional oceanic modeling system (ROMS) was used to reconstruct the background oceanic environment corresponding to three typhoon passages. Results show that the wide radius of maximum winds of typhoon Utor contributes to the strongest SST cooling by enhancing the Kuroshio intrusion (KI) onto the shelf northeast of Taiwan. Heat budget diagnostics explain why including tidal forcing can substantially promote SST cooling. The process was associated mainly with a stronger vertical advection tied to the influence of de-stratification by tidal mixing. Finally, warmer Taiwan Strait currents, driven by wind forcing the typhoons to pass zonally through the north South China Sea, intruded clockwise into the Longdong coast and accelerated the recovery of sea surface cooling around Longdong.

Temperature is vital in plant growth and agricultural fruit production. Litchi chinensis Sonn, commonly known as litchi, is appreciated for its delicious fruit and fragrant blossoms and is susceptible to stress when exposed to low temperatures. This study investigates the effect of two cryoprotectants that counteract cold stress during litchi flowering, identifies the genes that generate the cold resistance induced by the treatments, and hypothesizes the roles of these genes in cold resistance. Whole plants were treated with Bihu and Liangli cryoprotectant solutions to protect inflorescences below 10 °C. The soluble protein, sugar, fructose, sucrose, glucose, and proline contents were measured during inflorescence. Sucrose synthetase, sucrose phosphate synthetase, antioxidant enzymes (SOD, POD, CAT), and MDA were also monitored throughout the flowering stage. Differentially expressed genes (DEGs), gene ontology, and associated KEGG pathways in the transcriptomics study were investigated. There were 1243 DEGs expressed after Bihu treatment and 1340 in the control samples. Signal transduction pathways were associated with 39 genes in the control group and 43 genes in the Bihu treatment group. The discovery of these genes may contribute to further research on cold resistance mechanisms in litchi. The Bihu treatment was related to 422 low-temperature-sensitive differentially accumulated metabolites (DAMs), as opposed to 408 DAMs in the control, mostly associated with lipid metabolism, organic oxidants, and alcohols. Among them, the most significant differentially accumulated metabolites were involved in pathways such as β-alanine metabolism, polycyclic aromatic hydrocarbon biosynthesis, linoleic acid metabolism, and histidine metabolism. These results showed that Bihu treatment could potentially promote these favorable traits and increase fruit productivity compared to the Liangli and control treatments. More genomic research into cold stress is needed to support the findings of this study.

As the principal ligand for NKG2D, MICA elicits the recruitment of subsets of T cells and NK cells in innate immunity. MICA gene variants greatly impact the functionality and expression of MICA in humans. The current study evaluated whether MICA polymorphisms distinctively influence the pathogenesis of psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in Taiwanese subjects. The distributions of MICA alleles and levels of serum soluble NKG2D were compared between healthy controls and patients with PSO, RA, and SLE, respectively. The binding capacities and cell surface densities of MICA alleles were assessed by utilizing stable cell lines expressing four prominent Taiwanese MICA alleles. Our data revealed that MICA*010 was significantly associated with risks for PSO and RA (PFDR = 1.93 × 10−15 and 0.00112, respectively), while MICA*045 was significantly associated with predisposition to SLE (PFDR = 0.0002). On the other hand, MICA*002 was associated with protection against RA development (PFDR = 4.16 × 10−6), while MICA*009 was associated with a low risk for PSO (PFDR = 0.0058). MICA*002 exhibited the highest binding affinity for NKG2D compared to the other MICA alleles. Serum concentrations of soluble MICA were significantly elevated in SLE patients compared to healthy controls (p = 0.01). The lack of cell surface expression of the MICA*010 was caused by its entrapment in the endoplasmic reticulum. As a prevalent risk factor for PSO and RA, MICA*010 is deficient in cell surface expression and is unable to interact with NKG2D. Our study suggests that MICA alleles distinctively contribute to the pathogenesis of PSO, RA, and SLE in Taiwanese people.

ABSTRACT With the global prevalence of Varroa mites, more and more beekeepers resort to confining the queen bee in a queen cage to control mite infestation or to breed superior and robust queen bees. However, the impact of such practices on the queen bee remains largely unknown. Therefore, we subjected the queen bees to a 21-day egg-laying restriction treatment (from the egg stage to the emergence of adult worker bees) and analyzed the queen bees’ ovarian metabolites and gut microbiota after 21 days, aiming to assess the queen bees’ quality and assist beekeepers in better hive management. Our findings revealed a significant reduction in the relative expression levels of Vg and Hex110 genes in the ovaries of egg laying-restricted queen bees compared to unrestricted egg-laying queens. The diversity of gut microbiota in the queen bee exhibited a notable decrease, accompanied by corresponding changes in the core bacteria of the microbial community, the relative abundance of Lactobacillus and Bifidobacterium increased from 22.34% to 53.14% (P = 0.01) and from 0.053% to 0.580% (P = 0.04), respectively. The relative abundance of Bombella decreased from 25.85% to 1.720% (P = 0.002). Following egg-laying restriction, the activity of the queen bee’s ovaries decreased, while the metabolism of glycerophospholipids remained or stored more lipid molecules, awaiting environmental changes for the queen bee to resume egg laying promptly. Furthermore, we observed that Bombella in the queen bee’s gut may regulate the queen’s ovarian metabolism through tryptophan metabolism. These findings provide novel insights into the interplay among queen egg laying, gut microbiota, and ovarian metabolism. IMPORTANCE With Varroa mite infestation, beekeepers often confine the queen bee in cages for control or breeding. However, the impact on the queen bee is largely unknown. We evaluated queen bee quality by restricting egg laying and analyzing ovarian metabolites and gut microbiota. In this study, we provided a comprehensive explanation of the expression of ovarian genes, the diversity of gut microbiota, and changes in ovarian metabolism in the queen bee. Through integrated analysis of the queen bee’s gut microbiota and ovarian metabolism, we discovered that the gut microbiota can regulate the queen bee’s ovarian metabolism. These findings provide valuable insights into the interplay among egg laying, gut microbiota, and the reproductive health of the queen bee. Understanding these relationships can contribute to the development of better strategies for Varroa mite control and queen bee breeding.

A previously established flashing jet inhaler prototype (FJ prototype) can produce an aqueous aerosol but cannot steadily provide inhalable aerosol (2–5 μm). This study aims to optimize the atomization performance of the FJ prototype and generate inhalable aqueous aerosols. The effects of overheat degree, jetting rate, jetting volume, and liquid type on atomization performance were assessed by determining output aerosol's mass median aerodynamic diameter (MMAD) and aerodynamic particle size distribution. Drug distribution of active ingredients in different liquid types was also measured. A Pari nebulizer was used as a reference device. Our data suggested that MMAD is negatively correlated with the overheat degree and jetting rate, but has no significant relationship with the jetting volume. The effect of jetting rate is weaker than that of the overheat degree. When normal saline was used as the atomization liquid, output aerosol's MMAD at the FJ prototype and Pari nebulizer were 1.98 ± 0.18 and 2.50 ± 0.81 μm, respectively. The addition of a surfactant significantly decreases MMAD both in solution and in suspension, but the suspended particles had no effect on the residual level and atomization performance of the FJ prototype. When ventolin was used as the atomization liquid, the MMAD of the FJ prototype and Pari nebulizer was 2.1 ± 0.2 and 1.7 ± 0.2 μm, respectively, while the fine particle dosage (FPD) in percent of the nominal dose (%ND) was 50.4 ± 3.1 and 53.1 ± 7.2%, respectively. When pulmicort respules was used as the atomization liquid, the MMAD of the FJ prototype and Pari nebulizer was 2.5 ± 0.5 and 4.6 ± 0.2 μm respectively, while the FPD (%ND) was 30.1 ± 5.6 and 58.6 ± 5.1%, respectively. The FJ prototype not only delivers inhalable aqueous aerosol but also has a potential advantage in the atomization of suspension or poorly soluble drugs.