Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence.

The dual catalysis strategy is an efficient and powerful tool to fulfill the stereodivergent synthesis of stereoisomeric products from the same set of starting materials. Great attention has been given to the construction of chiral compounds with two contiguous stereocenters. However, the synthesis of two remote noncontiguous stereocenters is more challenging and is less developed, despite the high demand for synthetic tactics. We herein developed an unprecedented example of the stereodivergent preparation of synthetically useful and biologically important chiral ζ-hydroxy amino ester derivatives containing remote 1,6-noncontiguous stereocenters and a unique ß,γ-unsaturation moiety. This cascade dehydrogenation/1,6-Michael addition/hydrogenation protocol between readily-available ketoimine esters and racemic branched dienyl carbinols was rationally realized with bimetallic copper/ruthenium relay catalysis. The key features of the process were atom economy, step economy, and redox-neutrality. All four stereoisomers of chiral ζ-hydroxy amino ester derivatives were easily achieved by the orthogonal permutations of a chiral copper catalyst and chiral ruthenium catalyst. Importantly, a much more challenging stereodivergent synthesis of all eight stereoisomers of chiral peptide products containing three remote stereocenters was accomplished with excellent results through the cooperation of two chiral catalyst pairs and substrate enantiomers.

Enhancing aggregation of microalgae on polystyrene microplastics by high light: Processes, drivers, and environmental risk assessment.

Microplastics (MPs) are emerging pollutants, causing potential threats to aquatic ecosystems and serious concern in aggregating with microalgae (critical primary producers). When entering water bodies, MPs are expected to sink below the water surface and disperse into varying water compartments with different light intensities. However, how light influences the aggregation processes of algal cells onto MPs and the associated molecular coupling mechanisms and derivative risks remain poorly understood. Herein, we investigated the aggregation behavior between polystyrene microplastics (mPS, 10 µm) and Chlorella pyrenoidosa under low (LL, 15 µmol·m-2·s-1), normal (NL, 55 µmol·m-2·s-1), and high light (HL, 150 µmol·m-2·s-1) conditions from integrated in vivo and in silico assays. The results indicated that under LL, the mPS particles primarily existed independently, whereas under NL and HL, C. pyrenoidosa tightly bounded to mPS by secreting more protein-rich extracellular polymeric substances. Infrared spectroscopy analysis and density functional theory calculation revealed that the aggregation formation was driven by non-covalent interaction involving van der Waals force and hydrogen bond. These processes subsequently enhanced the deposition and adherence capacity of mPS and relieved its phytotoxicity. Overall, our findings advance the practical and theoretical understanding of the ecological impacts of MPs in complex aquatic environments.

Elucidating the regulatory role of long non-coding RNAs in drought stress response during seed germination in leaf mustard.

Leaf mustard (Brassica juncea L. Czern & Coss), an important vegetable crop, experiences pronounced adversity due to seasonal drought stress, particularly at the seed germination stage. Although there is partial comprehension of drought-responsive genes, the role of long non-coding RNAs (lncRNAs) in adjusting mustard's drought stress response is largely unexplored. In this study, we showed that the drought-tolerant cultivar 'Weiliang' manifested a markedly lower base water potential (-1.073 MPa vs -0.437 MPa) and higher germination percentage (41.2% vs 0%) than the drought-susceptible cultivar 'Shuidong' under drought conditions. High throughput RNA sequencing techniques revealed a significant repertoire of lncRNAs from both cultivars during germination under drought stress, resulting in the identification of 2,087 differentially expressed lncRNAs (DELs) and their correspondingly linked 12,433 target genes. It was noted that 84 genes targeted by DEL exhibited enrichment in the photosynthesis pathway. Gene network construction showed that MSTRG.150397, a regulatory lncRNA, was inferred to potentially modulate key photosynthetic genes (Psb27, PetC, PetH, and PsbW), whilst MSTRG.107159 was indicated as an inhibitory regulator of six drought-responsive PIP genes. Further, weighted gene co-expression network analysis (WGCNA) corroborated the involvement of light intensity and stress response genes targeted by the identified DELs. The precision and regulatory impact of lncRNA were verified through qPCR. This study extends our knowledge of the regulatory mechanisms governing drought stress responses in mustard, which will help strategies to augment drought tolerance in this crop.

Diagnosis of Alzheimer's disease: Towards accuracy and accessibility.

Alzheimer's disease (AD) is a serious dementia afflicting aging population and is characterized by cognitive decline, amyloid-ß plaques, and neurofibrillary tangles. AD substantially impairs the life quality of the victims and poses a heavy burden on the society at large. The number of people with dementia due to AD, prodromal AD, and preclinical AD is estimated to stand at roughly 3.2, 69, and 315 million worldwide, respectively. Current clinical diagnosis is based on clinical symptoms, and clinical research demonstrated that positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers had excellent diagnostic performance. However, the application of CSF biomarker tests and PET are restricted by the invasiveness and high cost. The presence of clinical symptoms means that AD pathology has been progressing for many years, and only a few drugs have been approved for the traetemnt of AD. Therefore, early diagnosis is extremely important for controlling the outcomes caused by AD. In this review, we provided an overview of developing clinical diagnostic criteria, diagnostic strategies under clinical research, developing blood based-biomarker assays, and promising nanotechnologically-based assays.

miRNAs: Primary modulators of plant drought tolerance.

Drought is a principal environmental factor that affects the growth and development of plants. Accordingly, plants have evolved adaptive mechanisms to cope with adverse environmental conditions. One of the mechanisms is gene regulation mediated by microRNAs (miRNAs). miRNAs are regarded as primary modulators of gene expression at the post-transcriptional level and have been shown to participate in drought stress response, including ABA response, auxin signaling, antioxidant defense, and osmotic regulation through downregulating the corresponding targets. miRNA-based genetic reconstructions have the potential to improve the tolerance of plants to drought. However, there are few precise classification and discussion of miRNAs in specific response behaviors to drought stress and their applications. This review summarized and discussed the specific response behaviors of miRNAs under drought stress and the role of miRNAs as regulators in the response of plants to drought and highlighted that the modification of miRNAs might effectively improve the tolerance of plants to drought.

Baseline neutrophil-to-lymphocyte ratio as a predictor of response to hospitalized bronchiectasis exacerbation risks.

Background: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization. Methods: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years. Results: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05). Conclusion: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Distribution Patterns and Antibiotic Resistance Profiles of Bacterial Pathogens Among Patients with Wound Infections in the Jiaxing Region from 2021 to 2023.

Purpose: To systematically assess the distribution and antimicrobial susceptibility of pathogens in wound infections, and analyze risk factors associated with multidrug resistance (MDR). Patients and Methods: Retrospectively analyzing Jiaxing-region medical records between January 2021 and December 2023, we identified a cohort of 461 wound infection patients. Cultures were grown on various agars, with bacteria identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. The antimicrobial susceptibility of the organisms were conducted by VITEK 2 system, Kirby-Bauer disk diffusion method and Epsilometer test. Statistical Package for the Social Sciences (SPSS) version 22 was used for statistical analysis. Multivariable logistic regression models were developed to pinpoint risk factors for multidrug-resistant organism (MDRO) infections and predict occurrences. Results: From 461 patients, 549 bacterial pathogens were isolated, predominantly consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, and Enterococcus faecalis. Vancomycin, linezolid, and tigecycline maintained their efficacy against Staphylococcus aureus and Enterococcus species, while Pseudomonas aeruginosa demonstrated sensitivity to aminoglycosides. Conversely, Escherichia coli exhibited high amoxicillin resistance (85.4%). More than half of the isolates were resistant to levofloxacin, ceftriaxone, cotrimoxazole, and gentamicin, with Acinetobacter baumannii strains showing considerable resistance (65.8-68.4%) to advanced cephalosporins and carbapenems. Within this group, 58 MDROs were detected, primarily originating from Burn Plastic Surgery, Emergency, and Intensive Care Unit (ICU) departments. Multivariate logistic regression identified hyperglycemia, hypoalbuminemia, surgery, extended hospitalization, and exposure to multiple antibiotic classes as independent risk factors for MDRO wound infections. Based on these findings, a predictive model for MDRO occurrence in wounds was constructed, which had a sensitivity of 0.627, specificity of 0.933, and an Area Under the Curve (AUC) of 0.838. Conclusion: Staphylococcus aureus and Pseudomonas aeruginosa dominated in wound infections with differential antibiotic resistance. Independent risk factors included hyperglycemia, hypoalbuminemia, surgery, extended hospitalization, and polyantibiotic use. We urge prioritizing culture, susceptibility tests, and personalized antibiotic strategies to address MDRO risks and improve wound infection management specificity and efficacy.

Cost-Effectiveness of Low-Dose Computed Tomography Screenings for Lung Cancer in High-Risk Populations: A Markov Model.

Background: Domestic and foreign studies on lung cancer have been oriented to the medical efficacy of low-dose computed tomography (LDCT), but there is a lack of studies on the costs, value and cost-effectiveness of the treatment. There is a scarcity of conclusive evidence regarding the cost-effectiveness of LDCT within the specific context of Taiwan. This study is designed to address this gap by conducting a comprehensive analysis of the cost-effectiveness of LDCT and chest X-ray (CXR) as screening methods for lung cancer. Methods: Markov decision model simulation was used to estimate the cost-effectiveness of biennial screening with LDCT and CXR based on a health provider perspective. Inputs are based on probabilities, health status utility (quality-adjusted life years (QALYs)), costs of lung cancer screening, diagnosis, and treatment from the literatures, and expert opinion. A total of 1,000 simulations and five cycles of Markov bootstrapping simulations were performed to compare the incremental cost-utility ratio (ICUR) of these two screening strategies. Probability and one-way sensitivity analyses were also performed. Results: The ICUR of early lung cancer screening compared LDCT to CXR is $-24,757.65/QALYs, and 100% of the probability agree to adopt it under a willingness-to-pay (WTP) threshold of the Taiwan gross domestic product (GDP) per capita ($35,513). The one-way sensitivity analysis also showed that ICUR depends heavily on recall rate. Based on the prevalence rate of 39.7 lung cancer cases per 100,000 people in 2020, it could be estimated that LDCT screening for high-risk populations could save $17,154,115. Conclusion: LDCT can detect more early lung cancers, reduce mortality and is cost-saving than CXR in a long-term simulation of Taiwan's healthcare system. This study provides valuable insights for healthcare decision-makers and suggests analyzing cost-effectiveness for additional variables in future research.

Clinical characteristics and analysis of vestibular-evoked myogenic potentials in patients with sudden sensorineural hearing loss in different ages.

BACKGROUND: Numerous studies have found that patients experiencing sudden sensorineural hearing loss (SSHL), with or without accompanying vertigo, often show impaired vestibular function. However, there is a dearth of studies analyzing vestibular-evoked myogenic potentials (VEMPs) in SSHL patients across various age groups. AIM: To investigate vestibular condition in SSHL patients across various age demographics. METHODS: Clinical data of 84 SSHL patients were investigated retrospectively. Audiometry, cervical vestibular evoked myogenic potentials (c-VEMPs), and ocular vestibular evoked myogenic potentials (o-VEMPs) were conducted on these patients. Parameters assessed included the latencies of P1 and N1 waves, as well as the amplitudes of P1-N1 waves. Moreover, the study evaluated the influence of factors such as sex, affected side, configuration of hearing loss, and presence of accompanying vertigo. RESULTS: Among the 84 SSHL patients, no significant differences were observed among the three groups in terms of gender, affected side, and the presence or absence of vertigo. Group II (aged 41-60 years) had the highest number of SSHL cases. The rates of absent o-VEMPs in the affected ears were 20.83%, 31.58%, and 22.72% for the three age groups, respectively, with no statistically significant difference among them. The rates of absent c-VEMPs in the affected ears were 8.3%, 34.21%, and 18.18% for the three age groups, respectively, with significant differences. In the unaffected ears, there were differences observed in the extraction rates of o-VEMPs in the unaffected ears among the age groups. In the three age groups, no significant differences were noted in the three age groups in the latencies of P1 and N1 waves or in the amplitude of N1-P1 waves for c-VEMPs and o-VEMPs, either on the affected side or on the unaffected side, across the three age groups. CONCLUSION: The extraction rate of VEMPs is more valuable than parameters. Regardless of the presence of vertigo, vestibular organs are involved in SSHL. Notably, SSHL patients aged 41-60 appear more susceptible to damage to the inferior vestibular nerve and saccule.

Effects of mixing water and environmental pH value on the properties of sulfoaluminate cement-based ultra-high water materials.

In order to grasp the influence of the pH value of mixing water and environmental water on the properties of ultra-high water materials, this article separately carried out the influence of different pH values of mixing water on the properties of ultra-high water materials and the conservation of high-water materials in water environments with different pH values. Using test methods such as loss of flow time, compressive strength, Scanning Electron Microscope (SEM), X-Ray Diffraction (XRD), Thermogravimetric-Differential Thermal Analysis (TG-DTA), to conduct regular exploration and mechanism analysis. The study found that with the continuous increase of the pH value of the mixing water, the loss of flow time of the ultra-high water material gradually decreased, and the compressive strength of the samples at the same age continued to increase. A lower pH value will affect the compressive strength of the consolidated body of the ultra-high water material, but when the pH = 13 in the reaction solution, the compressive strength of the consolidated body will no longer increase and begin to produce a weakening effect. The pH of the construction water for ultra-high water materials is recommended to be 4-13. At the same time, it was found that under the conservation of an acidic environment, the consolidated body was severely eroded and the strength loss was large. The acid-base environment of the goaf suitable for filling with the ultra-high water material should be between pH = 7-10 to ensure that the filling body is not weakened by erosion.

circPTP4A2 knockdown suppresses NSCLC progression via regulating proliferation and activating anti-tumor immunity.

BACKGROUND: With a considerable variety of cancer subtypes, Non-small cell lung cancer (NSCLC) poses a substantial threat to public health, affecting a large number of individuals and resulting in a high mortality rate. Circular RNA (circRNA) has been applied in various diseases, including cancers. This study aims to investigate the clinial significance and functional role of circPTP4A2 in NSCLC. METHODS: The serum and tissue samples were collected for detecting circPTP4A2 expression in NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Actinomycin D was used to treat NSCLC cells to detect circPTP4A2 stability. The CCK-8 and Transwell assays were utilized to assess the effects of circPTP4A2 in NSCLC cells. The ELISA assay and cytotoxicity analysis were used to detect the roles of circPTP4A2 in immune escape. RESULTS: The serum and tissue circPTP4A2 expression was upregulated in NSCLC. The high circPTP4A2 had a relatively high value in differentiating NSCLC patients from healthy individuals. The proliferation, invasion, and immune escape were repressed by circPTP4A2 knockdown. CONCLUSIONS: High circPTP4A2 has the potential to be a diagnostic biomarker in NSCLC. Silencing of circPTP4A2 receded the progression of NSCLC and enhanced antitumor immunity, which might provide potential targets and new ideas for improving the diagnosis and effect of immunotherapy in NSCLC patients.

A network meta-analysis of the effectiveness of different basic preconditioning regiments in allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To investigate and compare the effects of basic preconditioning regimens Bu/Cy, Cy/TBI and Flu/Bu for the treatment of patients in allogeneic hematopoietic stem cell transplantation. METHODS: It comprised exploring the published literature in the databases of PubMed, EMBASE, Cochrane Library, and Web of Science, using suitable keywords pertaining to various basic pretreatments Bu/Cy, Cy/TBI, and Flu/Bu, prior to allogeneic hematopoietic stem cell transplantation, and then extracting the searched outcome indicators of Overall Survival (OS) and survival (herein represented as OS and survival). Further, the results were estimated with meta-analysis using R, where the incidence of GVHD was reported in odds ratio (OR) with its 95% confidence interval (95%CI). RESULTS AND DISCUSSION: A total of 14 papers were included in this study, including 1436 cases were treated with Bu/Cy, 1816 cases with Cy/TBI, and 549 cases with Flu/Bu in the preconditioning regimen. After OS was the outcome pooled, compared with Flu/Bu in the preconditioning group, the results (Cy/TBI HR = 1.12 (95% Cl:1.04,1.61), Bu/Cy HR = 1.24 (95% Cl. 1.13,2.06)) showed that Flu/Bu preconditioning regimen significantly improved the overall survival rate of allogeneic HSCT patients. With the incidence of GVHD as the outcome summary, compared with Flu/Bu in the pretreatment group, the results (Cy/TBI HR = 1.24 (95% Cl:1.12, 1.82), Bu/Cy HR = 1.14 (95% Cl. 1.03, 2.12)) indicated that Flu/Bu in the pretreatment regimen group also significantly reduced the incidence of GVHD after allogeneic HSCT. CONCLUSION: Patients who received the basal preconditioning regimen Flu/Bu before allogeneic hematopoietic stem cell transplantation had the lowest hazard ratio for overall survival (OS) development. This indicates that the use of the basal preconditioning regimen Flu/Bu for the treatment of patients was the most effective, although the quality of the studies included needs to be confirmed by high-quality randomized controlled trials.

Inhalable Polymeric Microparticles for Phage and Photothermal Synergistic Therapy of Methicillin-Resistant Staphylococcus aureus Pneumonia.

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.

Development and reproduction of Scirtothrips dorsalis (Thysanoptera: Thripidae) on six host plant species.

Host plants can strongly influence the population performance of insects. Here, we investigated the development, survival, and oviposition of Scirtothrips dorsalis Hood on 6 host plants-Camellia sinensis ( L.) Kuntze (Ericales: Theaceae), Rosa chinensis Jacq. (Rosales: Rosaceae), Capsicum annuum L. (Solanales: Solanaceae), Eustoma grandiflorum (Hook.) G.Don (Gentianales: Gentianaceae), Glycine max (L.) Merr. (Fabales: Fabaceae), and Cucumis sativus L. (Cucurbitales: Cucurbitaceae), and constructed life tables for S. dorsalis on each plant. Significant differences in S. dorsalis development on the host species were observed. The mean developmental period from egg to adult was 11.45 ±â€…0.12 days, 11.24 ±â€…0.13 days, 12.08 ±â€…0.15 days, 12.28 ±â€…0.12 days, 12.67 ±â€…0.10 days, and 13.03 ±â€…0.11 days on C. sinensis, R. chinensis, C. annuum, E. grandiflorum, G. max, and C. sativus, respectively. Significant differences in survival of S. dorsalis were observed, namely, C. sinensis ≈ R. chinensis > E. grandiflorum ≈ C. annuum > G. max > C. sativus. The highest and lowest fecundities of S. dorsalis were recorded on R. chinensis (60.44 ±â€…1.53) and C. sativus (28.64 ±â€…1.02), respectively. Both of the net reproductive rate (R0) and intrinsic rate of increase (rm) of S. dorsalis were the highest on R. chinensis, with the values of 27.63 ±â€…0.58 and 0.142 ±â€…0.002, respectively; while the lowest on C. sativus, with the values of 8.81 ±â€…0.12 and 0.092 ±â€…0.003, respectively. Thus, R. chinensis was found to be the most suitable host, but C. sativus was the least suitable, for population development of S. dorsalis. Our results provide important information for the key control of S. dorsalis among different host plants.

Performance of P16INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for HPV-positive women aged 50 and above.

Background: Few articles have focused on the cytological misinterpretation of high-grade squamous intraepithelial lesion (HSIL). Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HSIL on Papanicolaou-stained cytology slides, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16 cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology. Objective: To evaluate the role of P16 cytology in differentiating cytology HSIL from benign atrophy in women aged 50 years and above. Methods: Included in this analysis were women in a cervical cancer screening project conducted in central China who tested positive for high-risk human papillomavirus (hr-HPV) and returned back for triage with complete data of primary HPV testing, liquid-based cytology (LBC) analysis, P16 immuno-stained cytology interpretation, and pathology diagnosis. The included patients were grouped by age: ≥50 (1,127 cases) and <50 years (1,430 cases). The accuracy of LBC and P16 cytology in the detection of pathology ≥HSIL was compared between the two groups, and the role of P16 immuno-stain in differentiating benign cervical lesions from cytology ≥HSIL was further analyzed. Results: One hundred sixty-seven women (14.8%; 167/1,127) in the ≥50 group and 255 (17.8%, 255/1,430) in the <50 group were pathologically diagnosed as HSIL (Path-HSIL). LBC [≥Atypical Squamous Cell Of Undetermined Significance (ASCUS)] and P16 cytology (positive) respectively detected 63.9% (163/255) and 90.2% (230/255) of the Path-≥HSIL cases in the <50 group and 74.3% (124/167) and 93.4% (124/167) of the Path-≥HSIL cases in the ≥50 group. LBC matched with pathology in 105 (41.2%) of the 255 Path-≥HSIL cases in the <50 group and 93 (55.7%) of the 167 Path-≥HSIL cases in the ≥50 group. There were five in the <50 group and 14 in the ≥50 group that were Path-≤LSIL cases, which were interpreted by LBC as HSIL, but negative in P16 cytology. Conclusion: P16 cytology facilitates differentiation of Path-≤LSIL from LBC-≥HSIL for women 50 years of age and above. It can be used in the lower-resource areas, where qualified cytologists are insufficient, as the secondary screening test for women aged ≥50 to avoid unnecessary biopsies and misinterpretation of LBC primary or secondary screening.

Stereodivergent synthesis of α-fluoro α-azaaryl γ-butyrolactones via cooperative copper and iridium catalysis.

The development of stereodivergent synthetic methods to access all four stereoisomers of biologically important α-fluoro γ-butyrolactones containing vicinal stereocenters is of great importance and poses a formidable challenge owing to ring strain and steric hindrance. Herein, a novel asymmetric [3+2] annulation of α-fluoro α-azaaryl acetates with vinylethylene carbonate was successfully developed through Cu/Ir-catalyzed cascade allylic alkylation/lactonization, affording a variety of enantioenriched α-fluoro γ-butyrolactones bearing vicinal stereogenic centers with high reaction efficiency and excellent levels of both stereoselectivity and regioselectivity (up to 98% yield, generally >20:1 dr and >99% ee). Notably, all four stereoisomers of these pharmaceutically valuable molecules could be accessed individually via simple permutations of two enantiomeric catalysts. In addition, other azaaryl acetates bearing α-methyl, α-chlorine or α-phenyl group were tolerated well in this transformation. Reaction mechanistic investigations were conducted to explore the process of this bimetallic catalysis based on the results of reaction intermediates, isotopic labelling experiments, and kinetic studies.

Associations of Urinary Heavy Metal Mixtures with High Remnant Cholesterol among US Adults: Evidence from the National Health and Nutrition Examination Survey (1998-2018).

The main objective of our study is to explore the associations between combined exposure to urinary heavy metals and high remnant cholesterol (HRC), a known cardiovascular risk factor. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we conducted a cross-sectional analysis of 5690 participants, assessing urinary concentrations of ten heavy metals. Ten heavy metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Fasting residual cholesterol ≥0.8 mmol/L was defined as HRC (using blood samples). Statistical analyses included weighted multivariable logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the associations of heavy metal exposure with HRC. Stratified analyses based on individual characteristics were also conducted. Multivariable logistic regression found that the four metals (OR Q4 vs. Q1: 1.33, 95% CI: 1.01-1.75 for barium (Ba); OR Q4 vs. Q1: 1.50, 95% CI: 1.16-1.94 for cadmium (Cd); OR Q4 vs. Q1: 1.52, 95% CI: 1.15-2.01 for mercury (Hg); OR Q4 vs. Q1: 1.35, 95% CI: 1.06-1.73 for lead (Pb)) were positively correlated with the elevated risk of HRC after adjusting for covariates. In addition, all three mixed models, including WQS (OR: 1.25; 95% CI: 1.07-1.46), qgcomp (OR: 1.17; 95% CI: 1.03-1.34), and BKMR, consistently showed a significant positive correlation between co-exposure to heavy metal mixtures and HRC, with Ba and Cd being the main contributors within the mixture. These associations were more pronounced in younger adults (20 to 59 years), males, and those with a higher body mass index status (≥25 kg/m2). Our findings reveal a significant relationship between exposure to the mixture of heavy metals and HRC among US adults, with Ba and Cd being the major contributors to the mixture's overall effect. Public health efforts aimed at reducing heavy metal exposure can help prevent HRC and, in turn, cardiovascular disease.

Association of smoking cessation patterns and untreated smoking with glaucoma, cataract, and macular degeneration: a population-based retrospective study.

This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.

Comparing Cancer Risks and Mortality between Phytopharmaceuticals and Estrogen-Progestogen Medications for Menopausal Women: A Population-Based Cohort Study.

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan's National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40-0.9] and 0.40 [0.16-0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36-0.92] and 0.33 [0.11-1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study.