Comparative Analysis of the Feasibility of Myocardial Blood Flow Index Versus CT-FFR in the Diagnosis of Suspected Coronary Artery Disease.

Background: Using fluid dynamic modeling, noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) data provides better anatomic and functional information than CCTA, with a high diagnostic and discriminatory value for diagnosing hemodynamically significant lesions. Myocardial blood flow index (MBFI) based on CCTA is a physiological parameter that reflects myocardial ischemia. Thus, exploring the relationship between computed tomography derived fractional flow reserve (CT-FFR) and MBFI could be clinically significant. This study aimed to investigate the relationship between CT-FFR and MBFI and to analyze the feasibility of MBFI differing from CT-FFR in diagnosing suspected coronary artery disease (CAD). Methods: Data from 61 patients (35 males, mean age: 59.2 ± 10.02 years) with suspected CAD were retrospectively analyzed, including the imaging data of CCTA, CT-FFR, and data of invasive coronary angiography performed within one week after hospitalization. CT-FFR and MBFI were calculated, and the correlation between MBFI or CT-FFR and invasive coronary angiography (ICA) was evaluated. Using ICA (value ≥ 0.70) as the gold standard and determining the optimal cutoff value via a diagnostic test, the diagnostic performance of MBFI or CT-FFR was evaluated. Results: MBFI and CT-FFR were negatively correlated with ICA (r = -0.3670 and -0.4922, p = 0.0036 and 0.0001, respectively). Using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.115 for MBFI, and the area under the curve (AUC) was 0.833 (95% confidence interval [CI]: 0.716-0.916, Z = 5.357, p < 0.0001); using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.80 for CT-FFR, and the area under the curve (AUC) was 0.759 (95% CI: 0.632-0.859, Z = 3.665, p = 0.0002). No significant difference was observed between the AUCs of CT-FFR and MBFI (Z = 0.786, p = 0.4316). Conclusions: MBFI based on CCTA can be used to evaluate myocardial ischemia similar to CT-FFR in suspected CAD; however, it should be noted that CT-FFR is a functional index based on the anatomical stenosis of the coronary artery, whereas MBFI is a physiological index reflecting myocardial mass remodeling.

Classification of Gastric Neuroendocrine Tumors and Associations With Survival.

BACKGROUND AND OBJECTIVES: Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes. METHODS: Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated. RESULTS: Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS. CONCLUSIONS: PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis.

The solute carrier transporters (SLCs) family in nutrient metabolism and ferroptosis.

Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due to the accumulation of lipid peroxides in response to various stimuli, such as high levels of iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial in regulating ferroptosis. The solute carrier transporters (SLCs) family, known as the "metabolic gating" of cells, is responsible for transporting intracellular nutrients and metabolites. Recent studies have highlighted the significant role of SLCs family members in ferroptosis by controlling the transport of various nutrients. Here, we summarized the function and mechanism of SLCs in ferroptosis regulated by ion, metabolic control of nutrients, and multiple signaling pathways, with a focus on SLC-related transporters that primarily transport five significant components: glucose, amino acid, lipid, trace metal ion, and other ion. Furthermore, the potential clinical applications of targeting SLCs with ferroptosis inducers for various diseases, including tumors, are discussed. Overall, this paper delves into the novel roles of the SLCs family in ferroptosis, aiming to enhance our understanding of the regulatory mechanisms of ferroptosis and identify new therapeutic targets for clinical applications.

The Protective Effects of Mcl-1 on Mitochondrial Damage and Oxidative Stress in Imiquimod-Induced Cancer Cell Death.

Mitochondria, vital organelles that generate ATP, determine cell fate. Dysfunctional and damaged mitochondria are fragmented and removed through mitophagy, a mitochondrial quality control mechanism. The FDA-approved drug IMQ, a synthetic agonist of Toll-like receptor 7, exhibits antitumor activity against various skin malignancies. We previously reported that IMQ promptly reduced the level of the antiapoptotic Mcl-1 protein and that Mcl-1 overexpression attenuated IMQ-triggered apoptosis in skin cancer cells. Furthermore, IMQ profoundly disrupted mitochondrial function, promoted mitochondrial fragmentation, induced mitophagy, and caused cell death by generating high levels of ROS. However, whether Mcl-1 protects mitochondria from IMQ treatment is still unknown. In this study, we demonstrated that Mcl-1 overexpression induced resistance to IMQ-induced apoptosis and reduced both IMQ-induced ROS generation and oxidative stress in cancer cells. Mcl-1 overexpression maintained mitochondrial function and integrity and prevented mitophagy in IMQ-treated cancer cells. Furthermore, IL-6 protected against IMQ-induced apoptosis by increasing Mcl-1 expression and attenuating IMQ-induced mitochondrial fragmentation. Mcl-1 overexpression ameliorates IMQ-induced ROS generation and mitochondrial fragmentation, thereby increasing mitochondrial stability and ultimately attenuating IMQ-induced cell death. Investigating the roles of Mcl-1 in mitochondria is a potential strategy for cancer therapy development.

Effects of different levels of physical activity on arterial stiffness and physical fitness performance in firefighters.

Background: Firefighters have lower levels of physical activity while on call. It is critical to understand the impact of firefighters' physical activity on arterial stiffness. This study classified groups by physical activity level and combined peripheral vascular monitor measurement to explore the relationships between the level of physical activity and cardiovascular (CV) risk and physical fitness (PF) of firefighters, as well as the acute response to arterial stiffness (AS) following maximal aerobic exercise test (MAET) intervention. Methods: The International Physical Activity Questionnaire (IPAQ) was used to classify the participants into 3 groups: low, moderate, and high level of physical activity group, respectively. A total of 36 participants were recruited, 12 in each group. Participants were assessed for body composition, rest brachial-ankle pulse wave velocity (baPWV), handgrip strength (HGS), maximal oxygen uptake (V̇O2max), and MAET baPWV. Results: In the three groups, significant differences were observed in V̇O2max, HGS, relative fat mass (%FM), body mass index (BMI), muscle mass ratio (MMR), and Rest baPWV (p < 0.05). After maximal aerobic exercise, the MAET baPWV values decreased significantly in all groups (all p < 0.001). Rest baPWV was significantly correlated with firefighters' age, seniority, metabolic equivalents (METs), height and muscle mass (MM) (p < 0.05). Conclusions: Firefighters with high levels of physical activity had better body composition and physical fitness and lower Rest baPWV. In all three groups, baPWV was lower after the MAET than before it. Therefore, regardless of a firefighter's level of physical activity, high-intensity aerobic exercise may have a beneficial effect on arterial stiffness.

Study to determine the efficacy and onset of Bonipar, a topical analgesic for the management of acute and chronic musculoskeletal pain.

BACKGROUND: Opioid abuse and mortality are ravaging American society, highlighting the need to find alternative effective analgesics with fewer side effects. FDA-approved topical analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), are commonly used to treat musculoskeletal pain but can cause adverse effects. Natural compounds, including essential oils, are potential therapeutic alternatives for managing musculoskeletal pain. If these compounds can provide comparable analgesia to FDA-approved products, it will increase the available options for people with pain, improving quality of life with minimal morbidity and mortality. OBJECTIVE: This study assesses the effectiveness and onset of action of Bonipar, a topical analgesic formulated with camphor, methyl salicylate, and oils of coconut, eucalyptus, nutmeg, and rosemary, in managing musculoskeletal pain compared to 1.5 % diclofenac solution, an FDA-approved topical non-steroidal anti-inflammatory drug. METHODS: One hundred sixty-four adult patients with localized musculoskeletal pain were randomly assigned to twice-daily applications of either Bonipar or Diclofenac for one week. The primary outcome measure was a 50 % reduction in pain after one week. Secondary outcomes included the change in pain from baseline and onset of action, defined as the first reduction in pain by 20 %. RESULTS: All patients completed the initial pain assessment to determine the onset of action. One-week data was available for 74 patients treated with diclofenac and 72 patients treated with Bonipar. Data for 18 patients were incomplete. The proportion of patients achieving a 50 % reduction in pain was statistically similar between the two groups. The success rates of achieving a 50 % pain reduction with Bonipar were found to be non-inferior to those treated with diclofenac. All follow-up time points showed roughly similar results between the groups. Regression models adjusted for age and sex revealed no significant effects on pain changes. Secondary analyses demonstrated no significant differences between the groups. DISCUSSION: The topical analgesic Bonipar demonstrates a comparable onset of action, with efficacy non-inferior to diclofenac in the management of musculoskeletal pain, while showing fewer adverse effects compared to diclofenac. These findings highlight the potential of Bonipar as a valuable alternative for the treatment of localized pain.

Identifying heterogeneous subgroups of systemic autoimmune diseases by applying a joint dimension reduction and clustering approach to immunomarkers.

BACKGROUND: The high complexity of systemic autoimmune diseases (SADs) has hindered precise management. This study aims to investigate heterogeneity in SADs. METHODS: We applied a joint cluster analysis, which jointed multiple correspondence analysis and k-means, to immunomarkers and measured the heterogeneity of clusters by examining differences in immunomarkers and clinical manifestations. The electronic health records of patients who received an antinuclear antibody test and were diagnosed with SADs, namely systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were retrieved between 2001 and 2016 from hospitals in Taiwan. RESULTS: With distinctive patterns of immunomarkers, a total of 11,923 patients with the three SADs were grouped into six clusters. None of the clusters was composed only of a single SAD, and these clusters demonstrated considerable differences in clinical manifestation. Both patients with SLE and SS had a more dispersed distribution in the six clusters. Among patients with SLE, the occurrence of renal compromise was higher in Clusters 3 and 6 (52% and 51%) than in the other clusters (p < 0.001). Cluster 3 also had a high proportion of patients with discoid lupus (60%) than did Cluster 6 (39%; p < 0.001). Patients with SS in Cluster 3 were the most distinctive because of the high occurrence of immunity disorders (63%) and other and unspecified benign neoplasm (58%) with statistical significance compared with the other clusters (all p < 0.05). CONCLUSIONS: The immunomarker-driven clustering method could recognise more clinically relevant subgroups of the SADs and would provide a more precise diagnosis basis.

Addressing the challenges of missed parathyroid glands in ultrasonography for secondary hyperparathyroidism: a retrospective observational study.

Purpose: Preoperative localization plays an important role in secondary hyperparathyroidism (SHPT) surgery. The advantages of neck ultrasound (US) include high availability and low cost. However, the reported sensitivity of US is 54%-76%, and the reason for missed parathyroid glands (PGs) on US has been rarely addressed. Methods: Fifty-four patients who were diagnosed with renal SHPT from September 2020 to March 2022 were included in this retrospective study. Preoperative localization included surgeon-oriented US and technetium 99m-sestamibi single-photon emission CT (SPECT)/CT. Results: A total of 212 PGs were pathologically confirmed, resulting in a success rate of 96.2% (52 of 54). Using echo, 193 PGs (91.0%) were accurately localized, while 19 glands (9.0%) were not identified, including those in ectopic positions (n = 12, at thymus or intrathyroid or others), of small size (<1 cm, n = 6), or overlapping with an ipsilateral PG (n = 1). US accurately detected 4 PGs in 36 (66.7%) patients, while SPECT/CT localized 4 glands in 19 patients (35.2%). Although the number of US-detectable PGs was not associated with success rate, it showed a significant negative correlation with surgical time (rs = -0.459, P = 0.002). Conclusion: US detected 4 glands in 66% of SHPT patients with a sensitivity of 90% for localization. Ectopic position and small size were the most common reasons for the failure to detect PG on US. Complete preoperative echo localization might shorten operating time.

Pneumatic tube transport-induced pseudohyperkalemia in patients with extreme leukocytosis: a retrospective study from a single medical center.

BACKGROUND: Pseudohyperkalemia (falsely elevated serum potassium) must be distinguished from true hyperkalemia to avoid unnecessary treatment. Some case reports suggest that pneumatic tube transportation may increase the risk of pseudohyperkalemia, but comprehensive research on the topic is lacking. Here, we aimed to assess the association between WBC levels, pneumatic tube transport, and pseudohyperkalemia prevalence. METHODS: We analyzed 1188 samples collected from 240 patients between 2019 and 2022. Samples with elevated WBC counts (≥ 100 × 103/µL) and potassium levels were included in this study. The method of specimen transportation was documented. RESULTS: Pseudohyperkalemia was observed (7/390) in specimens transported using pneumatic tubes. No pseudohyperkalemia was identified with manually transported specimens (0/132). Every increase in WBC count by 100 × 103/µL in the specimens multiplied the odds ratio of pseudohyperkalemia by 3.75 when delivered with pneumatic tube. The prevalence of pseudohyperkalemia increased as WBC count increased, especially at WBC counts greater than 200 × 103/µL. CONCLUSION: Pneumatic tube transport poses a risk for pseudohyperkalemia in patients with extreme leukocytosis. Physicians should anticipate odd potassium levels when interpreting blood test results. Redrawing of blood samples, manual specimen transportation, or point-of-care testing are suggested to prevent further misdiagnosis.

Association between pre-arrest left ventricular ejection fraction and survival in nontraumatic out-of-hospital cardiac arrest.

BACKGROUND AND IMPORTANCE: Out-of-hospital cardiac arrest (OHCA) poses major public health issues. Pre-arrest heart function is a prognostic factor, but the specific contribution of pre-arrest echocardiographic evaluation in predicting OHCA outcome remains limited. OBJECTIVE: The primary objective was to investigate the association between left ventricular ejection fraction (LVEF) measured in echocardiography prior to OHCA and survival to hospital discharge. DESIGN, SETTINGS, AND PARTICIPANTS: This multicenter retrospective cohort study analyzed data from the National Taiwan University Hospital and its affiliated hospitals. We included adult nontraumatic OHCA patients who were treated by the emergency medical services (EMS) and underwent echocardiography within 6 months prior to the OHCA event from January 2016 to December 2022. Data included demographics, preexisting diseases, resuscitation events, and echocardiographic reports. OUTCOMES MEASURE AND ANALYSIS: The primary outcome was the survival to hospital discharge after post-arrest care. Statistical analysis involved multivariable logistic regression to modify potential confounders, reported as adjusted odds ratio (aOR) and 95% confidence interval (CI), and evaluate the association between echocardiographic findings and survival to hospital discharge. MAIN RESULTS: This study analyzed 950 patients, with 33.6% surviving to discharge. A higher pre-arrest LVEF was independently associated with increased survival. Compared to patients with LVEF < 40%, those with LVEF between 40% and 60% had significantly higher odds of survival (aOR = 3.68, 95% CI = 2.14-6.35, P < 0.001), and those with LVEF > 60% had even greater odds of survival (aOR = 5.46, 95% CI = 3.09-9.66, P < 0.001). There was also an association between lower tricuspid regurgitation pressure gradient and survival (aOR = 0.98, 95% CI = 0.97-1.00, P = 0.015). Younger age, male gender, dyslipidemia, stroke, cancer, witnessed arrest, initial shockable rhythm, and shorter low-flow time are other significant predictors of survival. CONCLUSION: In adult, nontraumatic, EMS-treated OHCA patients, a higher LVEF 6 months prior to OHCA was associated with improved survival at hospital discharge.

Mental health needs and barriers to service in the Chinese American community: insights gained from focus groups.

OBJECTIVES: Mental health remains an unmet need among Chinese Americans. This study aims to identify specific needs and strategies that may address the needs. DESIGN: A total of 55 Chinese Americans consented and participated in online focus groups conducted in either Chinese or English using nominal group technique. Participants discussed the following questions, achieved themes, and provided ranking of themes in importance for each: (1) In general, what do people in the Chinese American community think about mental health or emotional well-being? (2) What have you found to be helpful for accessing mental health or emotional well-being services or care in the Chinese American population? And (3) What actions would you suggest to improve mental health and emotional well-being in the Chinese American population? RESULTS: Across the focus groups, we observed high consistency of top ranked themes including lack of knowledge and awareness, negative impression, lack of Chinese-speaking providers, and that the most helpful factor toward access to care was education and increased awareness. Seminars and trainings was the top actionable suggestion. CONCLUSION: The findings are consistent with previous findings and continue to show that Chinese Americans need more education and training and that providers who can speak the language and understand the culture would be very helpful to increase access to care. This study emphasizes addressing mental health disparities in the Chinese American community through awareness, tailored interventions, and barrier removal. Promoting equal access also underscores the need for ongoing assessment and responsive strategies.

Investigating effectiveness of adherence of long-acting bronchodilator in chronic obstructive pulmonary disease with influenza infection.

Objectives: Long-acting bronchodilators are important treatments for chronic obstructive pulmonary disease (COPD) and adequate medication adherence decreases COPD exacerbations, especially in reducing the hazard of influenza infection. Therefore, the study aim was to evaluate adherence of long-acting bronchodilator treatment and the risk of influenza in patients with COPD. Methods: This retrospective nested case-control study included patients with newly diagnosed COPD from 2012 to 2018. Cases with influenza infection were defined and matched to 2 randomly selected controls. The influenza infection date was the index date. Conditional logistic regressions were used to estimate odds ratios of influenza from proportion of days covered (PDC) of long-acting bronchodilators measured in one year before the index date. Adherence was divided into high adherence (PDC ≥80 %) and low adherence (PDC <80 %). Results: This population-based study included 6,073 patients in the case group and 12,146 in the control group. High PDC of long-acting bronchodilators in COPD was associated with a 0.811-fold (95 % confidence interval: 0.754-0.883, P < 0.001) decreased influenza risk, where 906 (14.92 %) high PDC in case and 2,130 (17.54 %) in control. Low PDC without influenza vaccination in COPD patients is associated with increased influenza risk, regardless of exposure period. Conclusion: In Taiwan, COPD patients with high PDC were associate with lower COPD exacerbation. Different long-acting bronchodilator exposure or dose need to be further investigated in COPD patients.

Nitrogen removal strategy for real swine wastewater by combining partial nitrification-denitrification process with anammox.

Anammox process offers reduced operational cost and energy requirement compared to nitrification-denitrification methods due to lower biomass generation and no need for external carbon sources and aeration. High ammonia concetration and low biodegradable anaerobic digester of swaine wastewater provided an advantage for the growth of anammox microorangism. An anoxic/oxic (A/O) SBR and an anammox SBR were implemented parallelly to treat the same swine wastewater with partial nitrification/denitrification and partial nitrification/anammox process, respectively, and to compare their nitrogen removal efficiency. The nitrogen removal rates (NRRs) of the A/O SBR and anammox SBR were 0.054 and 0.26 kg-N/m3/day, respectively. The lower NRR of the A/O SBR could be attributed to insufficient biodegradable organic carbon sources in the denitrification process. The kinetic parameters obtained from the two SBRs were applied to estimate the time required for using the A/O process and partial nitrification/anammox process to treat the same amount of ammonia with the same reaction volume. Results showed that the A/O process required 3.3 times the reaction time of the partial nitrification/anammox process, suggesting that the partial nitrification/anammox process is a more efficient and economic nitrogen removal process for swine wastewater treatment. The next generation sequencing results revealed that Candidatus Brocadia, ranging from 10 to 23%, was the predominant anammox bacteria in the anammox SBR. More than 78.2 % of nitrite in the anammox SBR was removed through the anammox reaction.

Large language model application in emergency medicine and critical care.

In the rapidly evolving healthcare landscape, artificial intelligence (AI), particularly the large language models (LLMs), like OpenAI's Chat Generative Pretrained Transformer (ChatGPT), has shown transformative potential in emergency medicine and critical care. This review article highlights the advancement and applications of ChatGPT, from diagnostic assistance to clinical documentation and patient communication, demonstrating its ability to perform comparably to human professionals in medical examinations. ChatGPT could assist clinical decision-making and medication selection in critical care, showcasing its potential to optimize patient care management. However, integrating LLMs into healthcare raises legal, ethical, and privacy concerns, including data protection and the necessity for informed consent. Finally, we addressed the challenges related to the accuracy of LLMs, such as the risk of providing incorrect medical advice. These concerns underscore the importance of ongoing research and regulation to ensure their ethical and practical use in healthcare.

Genetic variants associated with immune-mediated liver injury from checkpoint inhibitors.

BACKGROUND: The clinical features, liver histology, and genetic variants in 57 patients with moderate to severe immune-mediated liver injury from checkpoint inhibitors (ILICI) are presented. METHODS: Between 2010 and 2022, 57 high-causality ILICI cases were enrolled in the Drug-Induced Liver Injury Network. HLA and selected candidate gene variants were tested for association with ILICI risk compared to the general population and other DILI controls. RESULTS: The 57 high-causality cases were attributed to pembrolizumab (16), ipilimumab (15), ipilimumab and nivolumab (13), and other immune checkpoint inhibitors (13) and occurred at a median of 72 days after the first infusion. Median age was 57.8 years, 66% male, and 89% were non-Hispanic Whites. At DILI onset, 53% had hepatocellular, 35% mixed, and 15% cholestatic, with younger patients more likely to have hepatocellular injury. The incidence of ANA, smooth muscle antibody, and elevated IgG levels was low (17%, 23%, and 0%), but corticosteroids were given to 86%. Microgranulomas and hepatic steatosis were seen in 54% and 46% of the 26 liver biopsies, respectively. The HLA alleles associated with autoimmune hepatitis were not over-represented, but 2 host immune response genes (EDIL3 and SAMA5A) and 3 other genes (GABRP, SMAD3, and SLCO1B1) were associated with ILICI (OR: 2.08-2.4, p<0.01). CONCLUSIONS: ILICI typically arises within 12 weeks of initiating immunotherapy and is self-limited in most cases. Genetic variants involved in host T-cell regulation and drug disposition were identified, implicating these pathways in the pathogenesis of ILICI. If validated, these findings could lead to improved diagnostic instruments and possible treatments for ILICI.

Structure Prediction and Protein Engineering Yield New Insights into Microcin J25 Precursor Recognition.

Microcin J25 (MccJ25), a lasso peptide antibiotic with a unique structure that resembles the lariat knot, has been a topic of intense interest since its discovery in 1992. The precursor (McjA) contains a leader and a core segment. McjB is a protease activated upon binding to the leader, and McjC converts the core segment into the mature MccJ25. Previous studies suggested that these biosynthetic steps likely proceed in a (nearly) concerted fashion; however, there is only limited information regarding the structural and molecular intricacies of MccJ25 biosynthesis. To close this knowledge gap, we used AlphaFold2 to predict the structure of the precursor (McjA) in complex with its biosynthetic enzymes (McjB and McjC) and queried the critical predicted features by protein engineering. Based on the predicted structure, we designed protein variants to show that McjB can still be functional and form a proficient biosynthetic complex with McjC when its recognition and protease domains were circularly permutated or split into separate proteins. Specific residues important for McjA recognition were also identified, which permitted us to pinpoint a compensatory mutation (McjBM108T) to restore McjA/McjB interaction that rescued an otherwise nearly nonproductive precursor variant (McjAT-2M). Studies of McjA, McjB, and McjC have long been mired by them being extremely difficult to handle experimentally, and our results suggest that the AF2 predicted ternary complex structure may serve as a reasonable starting point for understanding MccJ25 biosynthesis. The prediction-validation workflow presented herein combined artificial intelligence and laboratory experiments constructively to gain new insights.

[5]Molecular Necklaces Formed Through Zn2+-Templated Binding of Macrocycles to Dynamically Formed Imines as Guest Recognition Sites.

Herein we demonstrate an "in-ring establishing" strategy for assembling interlocked molecules through dynamic imine formation, "establishing" the host recognition sites in situ. Using Zn2+ ions to template the assembly of a pyridine-containing macrocycle with semidumbbell-shaped triazole-containing aldehyde and amine derivatives, we obtained the corresponding [2]rotaxane in high yield (85%) after subsequent imine reduction (NaBH4) and amine protonation (NH4PF6). We performed the same three steps (assembly, reduction, protonation) to prepare a stable and highly symmetrical [5]molecular necklace ([5]MN) from 12 components (two almost-90°-oriented dialdehydes, two almost-90°-oriented diamines, four macrocycles, four Zn2+ ions) in an overall yield of 69%.

Fabrication of Stable Liquid-like Wetting Buckled Surfaces as Bioinspired Antibiofouling Coatings by Using Silicon-Containing Block Copolymers.

Inspired by animals with a slippery epidermis, durable slippery antibiofouling coatings with liquid-like wetting buckled surfaces are successfully constructed in this study by combining dynamic-interfacial-release-induced buckling with self-assembled silicon-containing diblock copolymer (diBCP). The core diBCP material is polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS). Because silicon-containing polymers with intrinsic characters of low surface energy, they easily flow over and cover a surface after it has undergone controlled thermal treatment, generating a slippery wetting layer on which can eliminate polar interactions with biomolecules. Additionally, microbuckled patterns result in curved surfaces, which offer fewer points at which organisms can attach to the surface. Different from traditional slippery liquid-infused porous surfaces, the proposed liquid-like PDMS wetting layer, chemically bonded with PS, is stable and slippery but does not flow away. PS-b-PDMS diBCPs with various PDMS volume fractions are studied to compare the influence of PDMS segment length on antibiofouling performance. The surface characteristics of the diBCPs─ease of processing, transparency, and antibiofouling, anti-icing, and self-cleaning abilities─are examined under various conditions. Being able to fabricate ecofriendly silicon-based lubricant layers without needing to use fluorinated compounds and costly material precursors is an advantage in industrial practice.

Data Independent Acquisition Mass Spectrometry Enhanced Personalized Glycosylation Profiling of Haptoglobin in Hepatocellular Carcinoma.

Aberrant glycosylation has gained significant interest for biomarker discovery. However, low detectability, complex glycan structures, and heterogeneity present challenges in glycoprotein assay development. Using haptoglobin (Hp) as a model, we developed an integrated platform combining functionalized magnetic nanoparticles and zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) for highly specific glycopeptide enrichment, followed by a data-independent acquisition (DIA) strategy to establish a deep cancer-specific Hp-glycosylation profile in hepatitis B virus (HBV, n = 5) and hepatocellular carcinoma (HCC, n = 5) patients. The DIA strategy established one of the deepest Hp-glycosylation landscapes (1029 glycopeptides, 130 glycans) across serum samples, including 54 glycopeptides exclusively detected in HCC patients. Additionally, single-shot DIA searches against a DIA-based spectral library outperformed the DDA approach by 2-3-fold glycopeptide coverage across patients. Among the four N-glycan sites on Hp (N-184, N-207, N-211, N-241), the total glycan type distribution revealed significantly enhanced detection of combined fucosylated-sialylated glycans, which were the most dominant glycoforms identified in HCC patients. Quantitation analysis revealed 48 glycopeptides significantly enriched in HCC (p < 0.05), including a hybrid monosialylated triantennary glycopeptide on the N-184 site with nearly none-to-all elevation to differentiate HCC from the HBV group (HCC/HBV ratio: 2462 ± 766, p < 0.05). In summary, DIA-MS presents an unbiased and comprehensive alternative for targeted glycoproteomics to guide discovery and validation of glyco-biomarkers.

Performances of full-scale biological nitrogen pre-treatment process for drinking water source: Seasonal variations and microbial community.

This study investigated the performance of the full-scale unit over a two-year period to enhance nitrification efficiency and provide operational strategies. Results indicated that raw water quality from Donggan River was notably influenced by seasonal variations, particularly during dry and wet seasons, impacting the nitrification efficiency of the biological pretreatment process. Factors such as influent concentrations of ammonia and total Kjeldahl nitrogen were found to have significant effects on nitrification, with temperature and conductivity also showing correlations. The specific rate of ammonia removal was calculated to be approximately 0.1 kg-N/m3/d under the existing operational setup. Moreover, elevating dissolved oxygen levels above 4 mg/L was proposed to potentially boost ammonia oxidation based on findings from experiments conducted in lab-scale bioreactors. In times of increased influent ammonia levels, the elimination of about 1-3 mg-N/L of total nitrogen signified the activation of denitrification processes. This observation was corroborated by results from next-generation sequencing techniques, verifying the existence of denitrifying microorganisms. The real-time PCR analysis results indicated that the abundance of comammox amoA gene was comparable with the abundance of the AOB amoA gene, indicating the presence of comammox Nitrospira and their potential role on nitrification in the system.