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BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

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OBJECTIVES: The purpose of this study was to investigate the association between cognitive impairments and traumatic upper limb injuries of the acute phase. MATERIAL AND METHODS: A cross-sectional observational study was conducted with three groups: a nerve-injury group, a without nerve injury group, and a control group (uninjured participants). Demographic characteristics (e.g. age, sex, body mass index, and education) and traumatic characteristics (duration since injury, injury side, pain, light touch sensation, hand motor function) were recorded. Short-term memory and executive functions were assessed using Rey Auditory and Verbal Learning Test (RAVLT) and Stroop Color and Word Test (SCWT, including SIECT and SIECN), respectively. RESULTS: The study comprised 43 participants in the nerve-injury group, 30 participants in the group without nerve injury, and 104 participants in the control group. Generalized linear model was applied to explore the difference of cognitive functions among three groups with impactors. Significantly poorer performance on the RAVLT was observed in the nerve-injury group compared to the other two groups, and lower score of SIECT in nerve-injury group was lower compared to the control group. However, there was no significant difference of SIECN among three groups. In addition, traumatic characteristics did not significantly impact RAVLT and SIECT (p > 0.05) in all injured participants. CONCLUSION: Traumatic nerve injury to the upper limb appears to be associated with both short-term memory and executive function impairment, whereas musculoskeletal injuries without nerve damage showed no cognitive impairment. Therefore, it is important to monitor cognitive function following upper limb nerve injuries.

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AIM: The aims of this study were to examine the effectiveness of a targeted nursing research support program for clinical nurses. BACKGROUND: Nursing research capacity is increasingly essential to clinical nurses and currently relatively low. Therefore, effective and systematic nursing research training programs are urgently needed to improve the scientific research abilities of nurses. METHODS: Qualitative research was conducted to investigate the effectiveness of a targeted nursing research support program. The program was formulated by considering the research training requirements of nurses and standard nursing research procedures, through literature review and group deliberations. The program was implemented for 973 nurses using a "plan-action-observation-reflection" learning cycle. The research outcomes achieved by nurses were evaluated and thematic analysis conducted to assess the perspectives of nurses and teachers regarding the research support program. RESULTS: Nurses participating in the targeted nursing research support program collectively accomplished 195 research proposals and authored 332 original research articles. Nurses shared their rich experience as "understanding my needs and achieving my potential", including: (1) systematic procedures and coherence; (2) easy to learn, easy to use; (3) a sense of belonging and mutual support; (4) self-confidence growth; and (5) high expectations. Further, the experiences of teachers were summarized as "helping others is helping myself", including: (1) teaching is learning; (2) the happiness of being needed; and (3) the importance of scientific teaching. CONCLUSION: This study evaluated the experiences of nurses and educators involved in a targeted nursing research support program and assessed its preliminary effectiveness. The findings revealed that the program, grounded in scientific and systematic research principles, was beneficial to both nurses and teachers. Based on our findings, we recommend that nursing educators should prioritize comprehensive, practice-integrated research training programs and create supportive environments, to effectively enhance the research capacity of nurses.

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BACKGROUND AND OBJECTIVE: To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). METHODS: Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. RESULTS: A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). CONCLUSIONS: Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

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OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

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BACKGROUND AND PURPOSE: NLRP3 is up-regulated in inflammatory and autoimmune diseases. The development of NLRP3 inhibitors is challenged by the identification of compounds with distinct mechanisms of action avoiding side effects and toxicity. Triptolide is a natural product with multiple anti-inflammatory activities, but a narrow therapeutic window. EXPERIMENTAL APPROACH: Natural product triptolide derivatives were screened for NLRP3 inhibitors in human THP-1 and mouse bone marrow-derived macrophages. The efficacy of potent NLRP3 inhibitors was evaluated in LPS-induced acute lung injury and septic shock models. KEY RESULTS: Triptolidiol was identified as a selective inhibitor of NLRP3 with high potency. Triptolidiol inactivated the NLRP3 inflammasome in human THP-1 and mouse primary macrophages primed with LPS. Triptolidiol specifically inhibited pro-caspase 1 cleavage downstream of NLRP3, but not AIM2 or NLRC4 inflammasomes. Based on the structure-activity relationship study, the C8-ß-OH group was critical for its binding to NLRP3. Triptolidiol exhibited a submicromolar KD for NLRP3, binding to residue C280. This binding prevented the interaction of NLRP3 with NEK7, the key regulator of NLRP3 inflammasome oligomerization and assembly, but not with the inflammasome adaptor protein ASC. Triptolidiol decreased the K63-specific ubiquitination of NLRP3, leading NLRP3 to a "closed" inactive conformation. Intraperitoneal administration of triptolidiol significantly attenuated LPS-induced acute lung injury and lethal septic shock. CONCLUSION AND IMPLICATIONS: Triptolidiol is a novel NLRP3 inhibitor that regulates inflammasome assembly and activation by decreasing K63-linked ubiquitination. Triptolidiol has novel structural features that make it distinct from reported NLRP3 inhibitors and represents a viable therapeutic lead for inflammatory diseases.

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In recent times, biochar has emerged as a novel approach for environmental remediation due to its exceptional adsorption capacity, attributed to its porous structure formed by the pyrolysis of biomass at elevated temperatures in oxygen-restricted conditions. This characteristic has driven its widespread use in environmental remediation to remove pollutants. When biochar is introduced into ecosystems, it usually changes the makeup of microbial communities by offering a favorable habitat. Its porous structure creates a protective environment that shields them from external pressures. Consequently, microorganisms adhering to biochar surfaces exhibit increased resilience to environmental conditions, thereby enhancing their capacity to degrade pollutants. During this process, pollutants are broken down into smaller molecules through the collaborative efforts of biochar surface groups and microorganisms. Biochar is also often used in conjunction with composting techniques to enhance compost quality by improving aeration and serving as a carrier for slow-release fertilizers. The utilization of biochar to support sustainable agricultural practices and combat environmental contamination is a prominent area of current research. This study aims to examine the beneficial impacts of biochar application on the absorption and breakdown of contaminants in environmental and agricultural settings, offering insights into its optimization for enhanced efficacy.

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BACKGROUND: The optimal approach for managing hepatic hemangioma is controversial. AIM: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience. METHODS: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated. RESULTS: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 (P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 (P > 0.05; χ² = 1.68, P > 0.05). CONCLUSION: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed.

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OBJECTIVE: To investigate the expression level of small nucleolar RNA (snoRNA) SNORA63 in bone marrow of patients with acute leukemia (AL) and its significance in the clinical diagnosis, treatment and prognosis of AL patients. METHODS: Bone marrow samples of 53 newly diagnosed AL patients and 29 healthy subjects in the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of SNORA63 in bone marrow mononuclear cells of the two groups. The median expression level of SNORA63 in AL patients was used as the boundary value to divide the patients into SNORA63 high and low expression groups, and the relationship between the expression level of SNORA63 and the clinical characteristics, clinical indicators and prognosis of AL patients was analyzed and discussed. RESULTS: The relative expression level of SNORA63 in AL patients was significantly lower than that in healthy control group [0.3018 (0.0244-1.2792) vs 1.0882 (0.2797-1.9889)] (P < 0.01). The expression level of SNORA63 in AL patients without remission after initial treatment was significantly lower than that in healthy controls and the patients who received complete remission (CR) (P < 0.01), while there was no statistical difference in the expression level of SNORA63 between AML and ALL groups (P >0.05). The abnormal low expression of SNORA63 was closely related to fever, hemorrage, poor prognosis, efficacy, platelets (PLT), lactate dehydrogenase (LDH), albumin (ALB), and molecular biological abnormalities of AL patients (P < 0.05), but not significantly correlated with sex, age, AL subtype, pallor, fatigue, extramedullary infiltration, white blood cell count (WBC), hemoglobin (HGB), C-reactive protein (CRP), procalcitonin (PCT), fibrinogen (FIB) or chromosome karyotype (P >0.05). Meanwhile, overall survival (OS) and event-free survival (EFS) of AL patients in SNORA63 high-expression group were significantly higher than those in SNORA63 low-expression group (P < 0.05). Univariate Cox regression analysis showed that SNORA63, molecular biological abnormalities, fever, PLT and LDH were the factors influencing OS and EFS in AL patients (P < 0.05). Multivariate Cox regression analysis indicated that fever, molecular biological abnormalities and LDH were independent factors associated with OS and EFS in AL patients (P < 0.05). CONCLUSION: SNORA63 is significantly down-expressed in AL patients, which is a molecular marker of great clinical value for disease monitoring and prognosis evaluation in AL patients.

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BACKGROUND/PURPOSE: Post-stroke dysphagia (PSD) is a common functional deficit after stroke. Temporal muscle thickness (TMT) had been proven to be an independent factor for PSD. However, the relationship between TMT and PSD based on quantitative swallowing kinematic analysis remains unexplored. We aimed to investigate the association between TMT and PSD using videofluoroscopic swallow study (VFSS). METHOD: We retrospectively recruited stroke patients from May 2015 to March 2020 in the tertiary referral hospital. A total of 83 patients with dysphagia met all the enrollment criteria and were included in the study. TMT was measured by non-contrast brain computed tomography (CT) images. Parameters of VFSS were obtained, including penetration-aspiration scale (PAS), oral transit time (OTT), pharyngeal transit time (PTT) and swallowing trigger time (STT) in four standardized barium formulas respectively. The association between TMT and variables of VFSS were analyzed by adjusted linear and logistic multivariate regression models. Subgroup analysis based on age, sex, and premorbid modified Rankin Scale (mRS) stratification was conducted. RESULTS: TMT was significantly correlated with gender and premorbid mRS as the confounders. Univariate regression showed smaller TMT (p = 0.010) and poorer premorbid mRS (p = 0.018) was associated with prolonged PTT of the thick formula; lesser TMT was associated with prolonged PTT of the paste formula (p = 0.037). Multivariate analyses after confounder-adjustment demonstrated TMT was an independent indicator for PTT in the thick formula (p = 0.028). CONCLUSIONS: TMT was associated with swallowing kinematic changes in patients diagnosed with PSD. TMT is an independent indicator for delayed pharyngeal stage in the thick standardized formula during deglutition in PSD patients.

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This study introduces a new NMR-based methodology for identification (ID) and quantification (purity, strength) assays of widely used amino acids. A detailed analysis of four amino acids and their available salts was performed with both a high-field (600 MHz) and a benchtop (60 MHz) NMR instrument. To assess sensitivity constraints, samples for 1H NMR analysis were initially prepared using only 10 mg of analyte and 1 mg of maleic acid (MA) as an internal calibrant (IC) and secondary chemical shift reference. The characteristic dispersion of the peak patterns indicating the presence or absence of a counterion (mostly chloride) was conserved at both high and low-field strength instruments, showing that the underlying NMR spectroscopic parameters, i.e., chemical shifts and coupling constants, are independent of the magnetic field strength. However, as the verbal descriptions of 1H NMR spectra are challenging in the context of reference materials and pharmaceutical monographs, an alternative method for the identification (ID) of amino acids is proposed that uses 13C NMR patterns from multiplicity-edited HSQC (ed-HSQC), which are both compound-specific and straightforward to document. For ed-HSQC measurements, the sample amount was increased to 30 mg of the analyte and several acquisition parameters were tested, including t1 increments used in the pulse program, number of scans, and repetition time. Excellent congruence with deviations <0.1 ppm was achieved for the 13C chemical shifts from 1D 13C NMR spectra (150 MHz) vs. those extracted from ed-HSQC (15 MHz traces). Finally, all samples of amino acid candidate reference materials were quantified by 1H qNMR (abs-qHNMR) at both 600 and 60 MHz. At high field, both IC and relative quantitations were performed, however, with the low-field instrument, only the IC method was used. The results showed that the analyzed reference material candidates were generally highly pure compounds. To achieve adequately low levels of uncertainty for such high-purity materials, the sample amounts were increased to 100 mg of analytes and 10 mg of the IC and replicates were analyzed for selected amino acids.

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BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

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OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

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AIMS: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) for the treatment of aortic regurgitation (AR). METHODS: From September 2019 to February 2022, 62 patients who underwent transfemoral TAVI procedure for pure, symptomatic severe AR with the VitaFlow system were enrolled in the current study. The outcomes were assessed according to the Valve Academic Research Consortium 3 criteria. Procedural results and clinical outcomes for 1 year were analyzed. RESULTS: The mean age was 71.56 ± 7.34 years and 58.1% were male. The mean Society of Thoracic Surgeons score was 5.44 ± 3.22%. The device success rate was 79.0%. Only one patient was converted to open surgery. The in-hospital mortality rate was 1.6%. The 1-year all-cause mortality rate was 6.5%. The new permanent pacemaker implantation rate was 29.0% in-hospital and 30.7% at 1-year follow-up. The second valve implantation rate was 14.5%. No patient developed more than moderate paravalvular leakage during follow-up. The mean ejection fraction improved from 54.05 ± 10.83% at baseline to 59.32 ± 8.70% (p < 0.001 compared with baseline) at 12 months. Left ventricular end-diastolic diameter decreased from 61.62 ± 5.58 mm at baseline to 55.20 ± 4.51 mm (p < 0.001 compared with the baseline) at 12 months. CONCLUSIONS: Transfemoral TAVI procedure shows efficacy in treating patients with severe pure native AR. The safety is improved with the development of the VitaFlow system.

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The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been widely used around the world in both agricultural and non-agricultural fields due to its high activity. However, the heavy use of 2,4-D has resulted in serious environmental contamination, posing a significant risk to non-target organisms, including human beings. This has raised substantial concerns regarding its impact. In addition to agricultural use, accidental spills of 2,4-D can pose serious threats to human health and the ecosystem, emphasizing the importance of prompt pollution remediation. A variety of technologies have been developed to remove 2,4-D residues from the environment, such as incineration, adsorption, ozonation, photodegradation, the photo-Fenton process, and microbial degradation. Compared with traditional physical and chemical remediation methods, microorganisms are the most effective way to remediate 2,4-D pollution because of their rich species, wide distribution, and diverse metabolic pathways. Numerous studies demonstrate that the degradation of 2,4-D in the environment is primarily driven by enzymatic processes carried out by soil microorganisms. To date, a number of bacterial and fungal strains associated with 2,4-D biodegradation have been isolated, such as Sphingomonas, Pseudomonas, Cupriavidus, Achromobacter, Ochrobactrum, Mortierella, and Umbelopsis. Moreover, several key enzymes and genes responsible for 2,4-D biodegradation are also being identified. However, further in-depth research based on multi-omics is needed to elaborate their role in the evolution of novel catabolic pathways and the microbial degradation of 2,4-D. Here, this review provides a comprehensive analysis of recent progress on elucidating the degradation mechanisms of the herbicide 2,4-D, including the microbial strains responsible for its degradation, the enzymes participating in its degradation, and the associated genetic components. Furthermore, it explores the complex biochemical pathways and molecular mechanisms involved in the biodegradation of 2,4-D. In addition, molecular docking techniques are employed to identify crucial amino acids within an alpha-ketoglutarate-dependent 2,4-D dioxygenase that interacts with 2,4-D, thereby offering valuable insights that can inform the development of effective strategies for the biological remediation of this herbicide.

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OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

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BACKGROUND: Circadian rhythm disruptions are a common concern for poststroke patients undergoing rehabilitation and might negatively impact their functional outcomes. OBJECTIVE: Our research aimed to uncover unique patterns and disruptions specific to poststroke rehabilitation patients and identify potential differences in specific rest-activity rhythm indicators when compared to inpatient controls with non-brain-related lesions, such as patients with spinal cord injuries. METHODS: We obtained a 7-day recording with a wearable actigraphy device from 25 poststroke patients (n=9, 36% women; median age 56, IQR 46-71) and 25 age- and gender-matched inpatient control participants (n=15, 60% women; median age 57, IQR 46.5-68.5). To assess circadian rhythm, we used a nonparametric method to calculate key rest-activity rhythm indicators-relative amplitude, interdaily stability, and intradaily variability. Relative amplitude, quantifying rest-activity rhythm amplitude while considering daily variations and unbalanced amplitudes, was calculated as the ratio of the difference between the most active 10 continuous hours and the least active 5 continuous hours to the sum of these 10 and 5 continuous hours. We also examined the clinical correlations between rest-activity rhythm indicators and delirium screening tools, such as the 4 A's Test and the Barthel Index, which assess delirium and activities of daily living. RESULTS: Patients who had a stroke had higher least active 5-hour values compared to the control group (median 4.29, IQR 2.88-6.49 vs median 1.84, IQR 0.67-4.34; P=.008). The most active 10-hour values showed no significant differences between the groups (stroke group: median 38.92, IQR 14.60-40.87; control group: median 31.18, IQR 18.02-46.84; P=.93). The stroke group presented a lower relative amplitude compared to the control group (median 0.74, IQR 0.57-0.85 vs median 0.88, IQR 0.71-0.96; P=.009). Further analysis revealed no significant differences in other rest-activity rhythm metrics between the two groups. Among the patients who had a stroke, a negative correlation was observed between the 4 A's Test scores and relative amplitude (ρ=-0.41; P=.045). Across all participants, positive correlations emerged between the Barthel Index scores and both interdaily stability (ρ=0.34; P=.02) and the most active 10-hour value (ρ=0.42; P=.002). CONCLUSIONS: This study highlights the relevance of circadian rhythm disruptions in poststroke rehabilitation and provides insights into potential diagnostic and prognostic implications for rest-activity rhythm indicators as digital biomarkers.

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Memantine is an US Food and Drug Administration (FDA) approved drug that selectively inhibits NMDA-subtype ionotropic glutamate receptors (NMDARs) for treatment of dementia and Alzheimer's. NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine blocks CP-AMPAR ion channels in a unique mechanism of action from NMDARs. Furthermore, we demonstrate that memantine reverses a gain of function AMPAR mutation found in a patient with a neurodevelopmental disorder and inhibits CP-AMPARs in nerve injury. Our findings alter the paradigm for the memantine mechanism of action and provide a blueprint for therapeutic approaches targeting CP-AMPARs.