Construction of an autofluorescence interference-free phosphorescence biosensor for the specific detection of TK1 mRNA.

The anti-interference ability of biosensors is critical for detection in biological samples. Fluorescence-based sensors are subject to interference from self-luminescent substances in biological matrices. Therefore, phosphorescent sensors stand out among biosensors due to their lack of self-luminescence background. In this study, a phosphorescent sensor was constructed, which can accurately detect thymidine kinase 1 (TK1) mRNA in biological samples and avoid autofluorescence interference. When there is no target, polydopamine (PDA) is used as the phosphorescence resonance energy transfer (PRET) acceptor to quench the phosphorescence of the persistently luminescent (PL) nanomaterial. When there is a target, the DNA modified by the PL nanomaterial is replaced by the hairpin H and removed away from the PDA, resulting in a rebound in phosphorescence. The phosphorescent sensor exhibits a good linear relationship in the TK1 mRNA concentration range of 0-200 nM, and the detection limit was 1.74 nM. The sensor fabricated in this study can effectively avoid interference from spontaneous fluorescence in complex biological samples, and sensitively and precisely detect TK1 mRNA in serum samples, providing a powerful tool to more accurately detect biomarkers in biological samples.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Infrared spectra and electronic structural changes of DNTF under high pressure: experimental and theoretical studies.

3,4-Bis(3-nitrofurazan-4-yl)furoxan (DNTF) is a novel energetic material with an excellent performance and has attracted considerable attention. Motivated by recent theories and experiments, we had carried out experimental and theoretical studies on the high-pressure responses of vibrational characteristics, in conjunction with structural and electronic characteristics. It is found that all observed infrared spectra peaks seem to shift towards higher frequencies. And the peaks attributed to N-Oc (coordinated oxygen atom) stretching vibrations become broader due to the decrease of lattice constants and the free region of DNTF crystals with the increase of pressure, where the a-direction is more sensitive to pressure. In addition, the non-covalent interaction between adjacent DNTF molecules in the same layer changes from the van der Waals interaction to the steric effect with the increase of pressure, and that between layers also changes from the van der Waals interaction to the π-π stacking interaction. More importantly, these results highlight that the increase of pressure may lead to the stability decrease and impact the sensitivity increase of DNTF. This study can deepen the understanding of the energetic material DNTF under high pressure and is of great significance for blasting and detonation applications of DNTF.

Fatty Liver, Statin Therapy, and the Risk of Hypertriglyceridemic Acute Pancreatitis: A Retrospective Study.

OBJECTIVES: Identifying patients with severe hypertriglyceridemia (HTG) who are prone to developing hypertriglyceridemic pancreatitis (HTGP) is essential for facilitating preventative interventions. This research aims to explore which part of the HTG patients is easy to develop into HTGP. MATERIALS AND METHODS: An observational cohort study was conducted in patients with serum triglycerides (TGs) ≥ 5.65 mmol/L. Propensity score matching (PSM) and logistic regression were used to adjust for potential confounding factors. Receiver operating characteristic (ROC) curves were applied to evaluate the predictive potential for HTGP. RESULTS: A total of 283 patients were included finally with a PSM cohort consisting of 55 HTGP matched with 77 non-HTGP. In multivariate logistic regression analysis, fatty liver (FL) (odds ratio, 2.535; P = 0.019) showed statistically significant association with HTGP, whereas statin use was correlated with a lower rate of HTGP (odds ratio, 0.203; P = 0.009). Finally, the ROC analysis showed that the TGs threshold thought to be causal of HTGP in patients with FL was significantly lower (9.31 vs 14.67 mmol/L) than that in patients without FL. CONCLUSIONS: Although with lower TGs levels, patients with FL are much more prone to generate HTGP, and our findings suggest a potential role of statin as protective agents against HTGP.

Divergent Evolutionary Rates of Primate Brain Regions as Revealed by Genomics and Transcriptomics.

Although the primate brain contains numerous functionally distinct structures that have experienced diverse genetic changes during the course of evolution and development, these changes remain to be explored in detail. Here we utilize two classic metrics from evolutionary biology, the evolutionary rate index (ERI) and the transcriptome age index (TAI), to investigate the evolutionary alterations that have occurred in each area and developmental stage of the primate brain. We observed a higher evolutionary rate for those genes expressed in the non-cortical areas during primate evolution, particularly in human, with the highest rate of evolution being exhibited at brain developmental stages between late infancy and early childhood. Further, the transcriptome age of the non-cortical areas was lower than that of the cerebral cortex, with the youngest age apparent at brain developmental stages between late infancy and early childhood. Our exploration of the evolutionary patterns manifest in each brain area and developmental stage provides important reference points for further research into primate brain evolution.

Outcomes of single-procedure radiofrequency catheter ablation for idiopathic ventricular arrhythmias: a single-centre retrospective cohort study.

OBJECTIVES: Radiofrequency catheter ablation is the first-line treatment for idiopathic premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). However, the outcomes were less compared among the categories. The study aims to assess the effectiveness and safety of catheter ablation for idiopathic PVC/VTs in a single high-volume centre, using the right ventricular outflow tract (RVOT) as a reference. DESIGN: Retrospective cohort study. SETTING: Patient data were collected from a tertiary hospital in Guizhou, China. PARTICIPANTS: Between September 2013 and September 2022, 1028 patients (male: 41.3%; age: 46.5±15.6 years) who underwent the first catheter ablation for idiopathic monomorphic PVC/VTs were enrolled. OUTCOME MEASURES: Acute success, procedure-related complications, and long-term recurrence were assessed. Antiarrhythmic drugs (AADs) were not administrated after procedures unless recurrence was identified. RESULTS: The overall acute success rate was 90.3%, with 368 patients (35.8%) experiencing left ventricular PVC/VTs. No cases of third-degree atrioventricular block or death were reported. Complications were more common in patients with left ventricular PVC/VTs than those with right-sided ones (4.6% vs 0.1%, p<0.001). A total of 926 patients (90.1%) were followed up for an average of 9.7±3.7 months, and only the PVC/VTs category was found to be associated with long-term success rates. The RVOT, endocardial left ventricular outflow tract (endoLVOT), tricuspid annulus (TA) free wall, posterior septum and fascicular VT had long-term success rates exceeding 85%. Other types of PVC/VTs showed significantly higher risks of recurrence. CONCLUSIONS: Besides RVOT and fascicular VT, single-procedure catheter ablation without AADs is highly effective for endoLVOT, TA-free wall and posterior septum. Patients with left ventricular PVC/VTs have higher complication risks compared with right ones.

Near fatal asthma in a case of allergic bronchopulmonary aspergillosis (ABPA) treated with ECMO.

BACKGROUND: Fatal asthma is a rapidly progressing and highly fatal form of asthma. Mechanical ventilation, although necessary for respiratory support, can exacerbate the condition and lead to ventilator-associated lung injury. ECMO therapy is crucial in allowing the lungs to rest and recover, as it provides extracorporeal membrane oxygenation. CASE PRESENTATION: A 40-year-old man presented with dyspnea following a mountain climb, which rapidly worsened, leading to respiratory failure and loss of consciousness. Despite drug therapy and mechanical ventilation, arterial blood gas analysis showed persistent hypercapnia. After 3 days of ECMO support, the patient was successfully extubated and underwent treatment for Aspergillus infection. Chest CT returned to normal after 3 months of anti-aspergillus therapy. CONCLUSION: When drug therapy and mechanical ventilation fail to improve respiratory failure in fatal asthma, prompt initiation of ECMO support is essential to create opportunities for subsequent etiological treatment.

Needs for mobile and internet-based psychological intervention in patients with self-injury and suicide-related behaviors: a qualitative systematic review.

BACKGROUND: In recent years, mobile psychological interventions have proven effective in reducing self-injury and suicide-related behaviors. Therefore, it is essential to continually enhance the user experience and address patients' needs to facilitate the development of mobile mental health interventions. Identifying patients with mobile mental health needs can be challenging for mental health professionals. To address this, we conducted a systematic review of qualitative research to synthesize the needs of patients engaged in self-injury and suicide-related behaviors for mobile and internet-based psychological interventions. METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and the Enhancing Transparency in Reporting the Synthesis of Qualitative Research statement (ENTREQ). We explored 11 databases and synthesized the results using thematic analysis. RESULTS: Sixteen qualitative and mixed-method studies were included. The study found that the needs of patients with self-injury and suicide-related behaviors for mobile psychological intervention included therapy, technology, culture, privacy, communication, emotional support, personalization, and self-management. Consistent with the Technology Acceptance Model (TAM), the needs of patients with self-injury and suicide-related behaviors are influenced by the perceived ease of use and perceived usefulness of the mobile intervention. However, the findings also highlight the importance and unmet needs of peer support, communication, self-management, and empowerment in using mobile psychological interventions for patients with self-injury and suicide-related behaviors. CONCLUSIONS: Studies in this area have shown that the needs of patients with self-harm and suicide-related behaviors cover multiple stages, including basic therapeutic and technical needs and advanced emotional needs. This complexity makes it challenging to address the needs of patients engaged in self-injury and suicide-related behaviors through digital interventions. In the future, mental health professionals should be encouraged to participate in multidisciplinary collaborations to expand the use of digital interventions, enhancing remote self-management for patients and providing new strategies for the ongoing care of psychiatric patients. We registered the review protocol on PROSPERO (CRD42022324958).

Efficacy and safety of Dimdazenil in adults with insomnia disorder: results from a multicenter, randomized, double-blind, placebo-controlled phase III trials.

STUDY OBJECTIVES: To evaluate the efficacy and safety of Dimdazenil, a novel partial positive allosteric modulator for GABAA receptor in adults with insomnia disorder. METHODS: This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study of Dimdazenil. The primary efficacy outcome was total sleep time (TST) analyzed by polysomnography (PSG) on day 13/14. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were analyzed in the same way by polysomnography (PSG). The other secondary outcomes including the average subjective sleep latency (sSL), subjective TST (sTST), subjective SE (sSE), subjective WASO (sWASO), and subjective number of awakenings (sNAW) were analyzed from sleep diary data, and the insomnia severity index (ISI) was also assessed. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. RESULTS: A total of 546 participants with insomnia (age ≥18 years) were randomized (2:1), received treatment with an oral dose of Dimdazenil (2.5 mg) or placebo, and analyzed. Compared to baseline and placebo, Dimdazenil demonstrated significant improvements in PSG measures, increased TST (71.09, 31.68 minutes, respectively; both p < 0.001), increased SE (13.26%, 5.55%, respectively; both < 0.001), reduced WASO (49.67, 20.16 minutes, respectively; both p < 0.001), and reduced LPS (21.65 minutes, p < 0.001; 6.46 minutes, p = 0.023). Compared to placebo, Dimdazenil also improved key self-reported measures of sTST (18.33 minutes, p < 0.001), sWASO (14.60 minutes, p < 0.001), sSL (4.23 minutes, p < 0.001), sSE (2.97%, p < 0.001), and sNAW (0.29, p < 0.001). Participants treated with Dimdazenil reported a significant improvement in ISI. Dimdazenil was well tolerated. The majority of TEAEs were mild or moderate. There were no clinically relevant treatment-related serious AEs and no deaths. CONCLUSIONS: Dimdazenil of 2.5 mg provided significant benefit on sleep maintenance and sleep onset in individuals with insomnia disorder versus placebo, with a favorable safety profile and was well tolerated. CLINICAL TRIAL INFORMATION: A multicenter, randomized, double-blind phase III clinical study evaluating the efficacy and safety of EVT201 capsules compared to placebo in patients with insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20201068.

Efficacy and safety of Dimdazenil in the adult insomnia patients: a phase II randomized, multicenter, double-blind, placebo-controlled, and parallel-group study.

STUDY OBJECTIVES: To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for α1, α5 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder. METHODS: In this randomized, double-blind, placebo-controlled trial, adults (18-65 years) with insomnia disorder were randomized (1:1:1:1 to receive daily oral placebo, Dimdazenil (1.5, 2.5, or 5 mg) for 14 days. The primary efficacy outcome was the total sleep time (TST) on day 1/2 and day 13/14, measured by polysomnography. The secondary outcome measures included (1) latency to persistent sleep (LPS), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NAW) on days 1/2 and day 13/14, and (2) the average subjective sleep latency (sSL), total sleep time (sTST), wake after sleep onset (sWASO) and number of awakenings (sNAW) recorded in sleep diary and sleep questionnaire, and the evaluation of insomnia severity index. Rebound insomnia, withdrawal, and treatment-emergent adverse events were also assessed. RESULTS: Of 569 patients screened, 288 (76.4% female) were randomized and received one dose. For the primary outcomes, TST was significantly improved in the Dimdazenil 1.5, 2.5, and 5 mg group compared with the placebo group at day 1/2, and significantly improved in the Dimdazenil 2.5 and 5 mg groups compared with the placebo group at day 13/14. The Least Squares Means (standard errors) and 95% Confidence Intervals for the three active doses compared to placebo are 25.5 (8.31), (9.16, 41.89) for the 1.5 mg dose; 17.4 (8.19), (1.29, 33.55) for the 2.5 mg dose; 22.8 (8.15), (6.72, 38.80) for the 5 mg dose on day 1/2. Corresponding data on day 13/14 are 7.6 (8.07), (-8.24, 23.53) and 19.3 (8.06), (3.43, 35.17) and 18.2 (7.95), (2.49, 33.80). LPS was significantly reduced in the Dimdazenil 5 mg group compared with the placebo group on day 1/2. SE was significantly improved in the Dimdazenil 1.5 and 5 mg group compared with the placebo group at day 1/2. In the subjective sleep parameters, sSL on average was significantly lower in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. sTST on average was significantly higher in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. The most common TEAEs were dizziness, vertigo, and weakness with no clinically relevant treatment-related serious adverse events. CONCLUSIONS: Dimdazenil of 1.5, 2.5, and 5 mg improved certain objective and subjective sleep outcomes in people with insomnia disorder, with a favorable safety profile. These findings suggested that Dimdazenil may represent a promising new treatment for insomnia disorder, a prevalent condition with limited effective and safe treatments available. CLINICAL TRIAL INFORMATION: A multicenter, randomized, double-blind, multidose, placebo parallel controlled phase II clinical study of EVT201 in the treatment of insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20150664.

Enhancing Nosocomial Infection Control through the Implementation of High-Quality Nursing Practices.

Background: Nosocomial infections pose a significant global health challenge. Effective nursing management plays a pivotal role in hospital administration, with the quality of nursing closely linked to nosocomial infection rates. Objective: This study explores the impact of implementing high-quality nursing practices on nosocomial infection control. Design: A randomized controlled experiment was conducted. Setting: The study was conducted at the Fourth Affiliated Hospital of Nanjing Medical University. Participants: Between December 2021 and December 2022, 120 hospitalized patients were selected and randomly assigned to the control and research groups, each comprising 60 patients. Interventions: The control group received routine nursing, while the research group received high-quality nursing. Primary Outcome Measures: (1) Infection incidence rate, (2) psychological state of patients, (3) bacterial culture qualified rate, (4) health knowledge awareness, (5) nursing quality, (6) quality of life, and (7) patient satisfaction. Results: The research group exhibited a significantly lower infection incidence rate compared to the control group (P < .05). No significant differences were observed between the groups before nursing (P > .05). Post-nursing, SAS, and SDS scores decreased in both groups, with a more pronounced reduction in the research group (P < .05). The research group demonstrated an increased qualified rate of bacterial culture in various environments compared to the control group (P < .05). After nursing, both groups showed higher scores in disease knowledge, nosocomial infection knowledge, treatment and rehabilitation knowledge, and self-care management knowledge, with the research group scoring higher than the control group (P < .05). Quality of life scores, nursing quality scores, and nursing satisfaction were all higher in the research group compared to the control group (P < .05). Conclusions: High-quality nursing practices emerge as the preferred choice in nosocomial infection control and prevention. It prioritizes patients' wishes and needs, offers comprehensive services, and respects patient autonomy; these measures contribute to a substantial reduction in nosocomial infections.

Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy.

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Single-crystal ZrCo nanoparticle for advanced hydrogen and H-isotope storage.

Hydrogen-isotope storage materials are essential for the controlled nuclear fusion. However, the currently used smelting-ZrCo alloy suffers from rapid degradation of performance due to severe disproportionation. Here, we reveal a defect-derived disproportionation mechanism and report a nano-single-crystal strategy to solve ZrCo's problems. Single-crystal nano-ZrCo is synthesized by a wet-chemistry method and exhibits excellent comprehensive hydrogen-isotope storage performances, including ultrafast uptake/release kinetics, high anti-disproportionation ability, and stable cycling, far superior to conventional smelting-ZrCo. Especially, a further incorporation of Ti into nano-ZrCo can almost suppress the disproportionation reaction. Moreover, a mathematical relationship between dehydrogenation temperature and ZrCo particle size is established. Additionally, a microwave method capable of nondestructively detecting the hydrogen storage state of ZrCo is developed. The proposed disproportionation mechanism and anti-disproportionation strategy will be instructive for other materials with similar problems.

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis (NASH). DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule (SG) and pro-death NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly in response to stress signals. However, the role of DDX3X in NASH remains unclear. We characterized the cell type-specific roles of DDX3X in NASH. Human liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and distribution. Nutritional steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout (DDX3XΔMφ), hepatocyte-specific DDX3X knockout (DDX3XΔhep), and wild-type control (DDX3Xfl/fl) mice a high-fat and high-cholesterol (HFHC) diet, a methionine- and choline-deficient (MCD) diet, and a high-fat/high-iron/high-fructose/high-cholesterol, low-methionine, and choline-deficient (HFHIHFHC-MCD) diet. The study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues, and its expression was down-regulated in patients or mice with NASH. Compared to DDX3Xfl/fl littermates, DDX3XΔMφ mice showed improved liver histology in nutritional steatohepatitis models. Loss of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis, causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic changes. DDX3XΔhep mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3Xfl/fl littermates. DDX3X-deleted hepatocytes showed impaired SG assembly, leading to increased sensitivity and intolerance to metabolic stimulation and resultant steatohepatitis. In conclusion, DDX3X plays opposite roles in different cell types during the progression of NASH. A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing prospective targeted DDX3X inhibitors for the treatment of NASH.

Muc2 mucin O-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. METHODS: A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. RESULTS: Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the O-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or O-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of O-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of O-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. CONCLUSIONS: Together, there exist complex interactions between the intestinal epithelium, O-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis.

Comprehensive Assessment of Reactive Bromine Species in Advanced Oxidation Processes: Differential Roles in Micropollutant Abatement in Bromide-Containing Water.

Reactive bromine species (RBS) are gaining increasing attention in natural and engineered aqueous systems containing bromide ions (Br-). However, their roles in the degradation of structurally diverse micropollutants by advanced oxidation processes (AOPs) were not differentiated. In this study, the second-order rate constants (k) of Br•, Br2•-, BrO•, and ClBr•- were collected and evaluated. Br• is the most reactive RBS toward 21 examined micropollutants with k values of 108-1010 M-1 s-1. Br2•-, ClBr•-, and BrO• are selective for electron-rich micropollutants with k values of 106-108 M-1 s-1. The specific roles of RBS in aqueous micropollutant degradation in AOPs were revealed by using simplified models via sensitivity analysis. Generally, RBS play minimal roles in the UV/H2O2 process but are significant in the UV/peroxydisulfate (PDS) and UV/chlorine processes in the presence of trace Br-. In UV/PDS with ≥1 µM Br-, Br• emerges as the major RBS for removing electron-rich micropollutants. In UV/chlorine, BrO• contributes to the degradation of specific electron-rich micropollutants with removal percentages of ≥20% at 1 µM Br-, while the contributions of BrO• and Br• are comparable to those of reactive chlorine species as Br- concentration increases to several µM. In all AOPs, Br2•- and ClBr•- play minor roles at 1-10 µM Br-. Water matrix components such as HCO3-, Cl-, and natural organic matter (NOM) significantly inhibit Br•, while BrO• is less affected, only slightly scavenged by NOM with a k value of 2.1 (mgC/L)-1 s-1. This study sheds light on the differential roles of multiple RBS in micropollutant abatement by AOPs in Br--containing water.

Ultra-Sensitive Portable Visual Paper-Based Viral Molecularly Imprinted Sensor without Autofluorescence Interference.

Detection of the virus is the primary factor to discover and block the occurrence and development of the virus epidemic. Here, an ultrasensitive paper-based virus molecular imprinting sensor is developed to detect two viruses simultaneously in which the detection limit of the influenza virus (H5N1) is 16.0 aM (9.63 × 103 particles/mL) while that of the Hepatitis B Virus (HBV) is 129 fM (7.77 × 107 particles/mL). This paper-based sensor is low cost and is easy to cut, store, and carry. In addition, the visual semiquantitative detection of two viruses is achieved by using two aptamer-functionalized persistent luminescent nanoparticles as signal probes. These probes and the imprinted cavities on the paper-based material formed sandwich-type double recognition of the target viruses. This sensor has extremely high sensitivity to the H5N1 virus, which is of great value to solve the influenza epidemic with the most outbreaks in history, and also opens up a new way for the prevention and control of other virus epidemics. This cheap and portable visual sensor provides the possibility for self-service detection and can greatly reduce the pressure on medical staff and reduce the risk of virus infection caused by the concentration of people to be tested.

Comparison between the modified long gonadotropin-releasing hormone agonist protocol and the non-downregulation protocol in POSEIDON groups: a propensity score matching retrospective cohort study.

Background: In vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes. Objectives: This study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group. Design: This study was designed as a propensity score-matched (PSM) retrospective analysis. Participants: The study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology. Methods: The patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups. Results: Of the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779). Conclusions: The modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients. Level of evidence: Level III.

Efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells for the treatment of complex perianal fistula in Crohn's disease: a pilot study.

OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) for complex perianal fistula in patients with Crohn's disease (CD). METHODS: This was an open-label, single-arm clinical trial conducted at Jinling Hospital. Adult patients with complex treatment-refractory CD perianal fistulas (pfCD) were enrolled and received a single intralesional injection of 120 million TH-SC01 cells. Combined remission was defined as an absence of suppuration through an external orifice, complete re-epithelization, and absence of collections larger than 2 cm measured by magnetic resonance imaging (MRI) at 24 weeks after cell administration. RESULTS: A total of 10 patients were enrolled. Six patients (60.0%) achieved combined remission at 24 weeks. The number of draining fistulas decreased in 9 (90.0%) and 7 (70.0%) patients at weeks 12 and 24, respectively. Significant improvement in Perianal Crohn Disease Activity Index, Pelvic MRI-Based Score, Crohn Disease Activity Index, and quality of life score were observed at 24 weeks. No serious adverse events occurred. The probability of remaining recurrence-free was 70% at week 52. CONCLUSION: The study demonstrated that local injection of TH-SC01 cells might be an effective and safe treatment for complex treatment-refractory pfCD after conventional and/or biological treatments fail (ClinicalTrials.gov ID, NCT04939337). TRIAL REGISTRATION: The study was retrospectively registered on www. CLINICALTRIALS: gov (NCT04939337) on June 25, 2021.

Tanshinol alleviates ischemia-induced myocardial fibrosis via targeting ERK2 and disturbing the intermolecular autophosphorylation of ERK2Thr188.

Myocardial fibrosis is the fundamental remodeling process in myocardial ischemia (MI) and also the major contributor of heart failure and death. Tanshinol (Danshensu in Chinese, DSS), a major ingredient of salvia mitiorrhiza Bunge (Lamiaceae) root, exerted significant cardio protection effects. In this study, we aimed to identify the action target and then uncover the mechanism of DSS alleviating myocardial fibrosis. The pharmacological activities of DSS protecting ischemic cardiac was assessed and the myocardial proteomics was carried out. To identify the target of DSS, a cellular thermal shift assay combined with LC-MS identification was conducted. Surface plasmon resonance assay, molecular dynamics simulation and pharmacological and molecular biology approaches were adopted to explore the action mechanisms of DSS. Our results revealed that DSS effectively alleviated MI-induced left ventricle dysfunctions and the increasements of circulating myocardial markers. Besides, DSS significantly reversed the proteomic profile related to myocardial fibrotic processes and the ERK2 was identified as a crucial cellular target of DSS. DSS abated the temperature-dependent denaturation of ERK2 in a dose-dependent manner and the KD value of DSS and ERK2 was 60.19 µM. After Ang II stimulation, DSS suppressed the phosphorylation of Thr188 rather than the classic residues in TEY motif. DSS interfered the ERK2 homo-dimerization and then blocked the intermolecular autophosphorylation at Thr188 site. Thereout, DSS inhibited the nuclear translocation of ERK2 and the expression of downstream fibrotic biomolecules. Collectively, our results demonstrated that DSS targeted ERK2 and suppressed the intermolecular autophosphorylation at Thr188 residue, thus protecting ischemic myocardia from fibrosis remodeling.