InDEP: an interpretable machine learning approach to predict cancer driver genes from multi-omics data.

Cancer driver genes are critical in driving tumor cell growth, and precisely identifying these genes is crucial in advancing our understanding of cancer pathogenesis and developing targeted cancer drugs. Despite the current methods for discovering cancer driver genes that mainly rely on integrating multi-omics data, many existing models are overly complex, and it is difficult to interpret the results accurately. This study aims to address this issue by introducing InDEP, an interpretable machine learning framework based on cascade forests. InDEP is designed with easy-to-interpret features, cascade forests based on decision trees and a KernelSHAP module that enables fine-grained post-hoc interpretation. Integrating multi-omics data, InDEP can identify essential features of classified driver genes at both the gene and cancer-type levels. The framework accurately identifies driver genes, discovers new patterns that make genes as driver genes and refines the cancer driver gene catalog. In comparison with state-of-the-art methods, InDEP proved to be more accurate on the test set and identified reliable candidate driver genes. Mutational features were the primary drivers for InDEP's identifying driver genes, with other omics features also contributing. At the gene level, the framework concluded that substitution-type mutations were the main reason most genes were identified as driver genes. InDEP's ability to identify reliable candidate driver genes opens up new avenues for precision oncology and discovering new biomedical knowledge. This framework can help advance cancer research by providing an interpretable method for identifying cancer driver genes and their contribution to cancer pathogenesis, facilitating the development of targeted cancer drugs.

Assessment of nucleic acid extraction protocols for antibiotic resistance genes (ARGs) quantification in aircraft wastewater.

This study evaluated ten nucleic acid extraction protocols (EP1 to EP10) for measuring five endogenous antibiotic resistance genes (ARGs) in four aircraft wastewater samples (AWW1 to AWW4). The targeted ARGs, including blaCTX-M, blaNDM-1, ermB, qnrS, and tetA, encompassed highly and minimally abundant ARGs. TetA and ermB were consistently detected across four aircraft wastewater samples using the DNeasy Blood and Tissue Kit and the AllPrep PowerViral DNA/RNA kit. QnrS displayed high detection rates with specific extraction protocols and aliquot volumes. Concentrations of ARGs varied across aircraft wastewater samples, with differing extraction protocols influencing quantitative results. The concentrations of tetA, ermB, and qnrS in AWW1 were distinct, while AWW2 to AWW4 exhibited a broader range for tetA, ermB, qnrS, blaCTX-M, and blaNDM-1. EP1 consistently produced the highest concentrations for several ARGs. Collective data analysis revealed varying ARG concentrations across the ten extraction protocols, suggesting the importance of careful extraction protocol selection in ARG monitoring in aircraft wastewater samples. Based on the results, we suggest that a small sample volume (as low as 0.2 mL) may be sufficient for ARG characterization in aircraft wastewater samples. The findings also emphasize the need for considering toilet paper removal without compromising nucleic acid extraction efficiency. The study highlights promising prospects for aircraft wastewater monitoring of ARGs, calling for further investigation into the import and spread of unique ARGs through transport hubs.

Sulphated Fucooligosaccharide from Sargassum Horneri: Structural Analysis and Anti-Alzheimer Activity.

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.

Cinnamic Acid: A Low-Toxicity Natural Bidentate Ligand for Uranium Decorporation.

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.

Natural Products of Licorice for Uranium Decorporation with Low Toxicity and High Efficiency.

The development and exploration of uranium decorporation agents with straightforward synthesis, high removal ability, and low toxicity are crucial guarantees for the safety of workers in the nuclear industry and the public. Herein, we report the use of traditional Chinese medicine licorice for uranium decorporation. Licorice has good adsorption performance and excellent selectivity for uranium in the simulated human environment. Glycyrrhizic acid (GL) has a high affinity for uranium (p(UO2) = 13.67) and will complex with uranium at the carbonyl site. Both licorice and GL exhibit lower cytotoxicity compared to the commercial clinical decorporation agent diethylenetriamine pentaacetate sodium salts (CaNa3-DTPA). Notably, at the cellular level, the uranium removal efficiency of GL is eight times higher than that of CaNa3-DTPA. Administration of GL by prophylactic intraperitoneal injection demonstrates that its uranium removal efficiency from kidneys and bones is 55.2 and 23.9%, while CaNa3-DTPA shows an insignificant effect. The density functional theory calculation of the bonding energy between GL and uranium demonstrates that GL exhibits a higher binding affinity (-2.01 vs -1.15 eV) to uranium compared to DTPA. These findings support the potential of licorice and its active ingredient, GL, as promising candidates for uranium decorporation agents.

Association of the live microbe intake from foods with all-cause and cardiovascular disease-specific mortality: a prospective cohort study.

BACKGROUND: Live dietary microbes have been hypothesized to promoting human health. However, there has been lacking perceptions to crystallize nexus between consumption of foods with live microbes and mortality. OBJECTIVE: To investigate the association of consumption of foods with medium to high amounts of live microbes with all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. METHODS: The data were obtained from the National Health and Nutrition Examination Survey 1999-2018 at baseline linked to the 2019 National Death Index records. Based on consumption of foods that were categorized as either having medium or high microbial content (MedHi foods), participants were classified into three groups. Kaplan-Meier survival curves and multivariable Cox regression models were used to estimate the association of consumption of MedHi foods with mortality. Population-attributable fractions (PAFs) of consumption of MedHi foods in relation to mortality risk were also estimated. RESULTS: A total of 35,299 adults aged ≥ 20 years were included in this study. During a median follow-up of 9.67 years, compared with adults in G1, those in G3 had 16% (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.77-0.90) reduced risk of all-cause mortality, and 23% (HR, 0.77; 95% CI, 0.67-0.89) reduced risk of CVD-specific mortality. The PAF of high (G3) vs. intermediate or low consumption of MedHi foods (G1 + G2) with all-cause and CVD-specific mortality was 3.4% and 4.3%, respectively. CONCLUSIONS: Consumption of foods with higher microbial concentrations is associated with a reduced risk of all-cause and CVD-specific mortality in US adults.

Ultrasensitive electrochemical sensor based on synergistic effect of Ag@MXene and antifouling cyclic multifunctional peptide for PD-L1 detection in serum.

A sensing interface co-constructed from the two-dimensional conductive material (Ag@MXene) and an antifouling cyclic multifunctional peptide (CP) is described. While the large surface area of Ag@MXene loads more CP probes, CP binds to Ag@MXene to form a fouling barrier and ensure the structural rigidity of the targeting sequence. This strategy synergistically enhances the biosensor's sensitivity and resistance to contamination. The SPR results showed that the binding affinity of the CP to the target was 6.23 times higher than that of the antifouling straight-chain multifunctional peptide (SP) to the target. In the 10 mg/mL BSA electrochemical fouling test, the fouling resistance of Ag@MXene + CP (composite sensing interface of CP combined with Ag@MXene) was 30 times higher than that of the bare electrode. The designed electrochemical sensor exhibited good selectivity and wide dynamic response range at PD-L1 concentrations from 0.1 to 50 ng/mL. The lowest detection limit was 24.54 pg/mL (S/N = 3). Antifouling 2D materials with a substantial specific surface area, coupled with non-straight chain antifouling multifunctional peptides, offer a wide scope for investigating the sensitivity and antifouling properties of electrochemical sensors.

Tunable Au@SiO2/Au Film Metasurface as Surface Plasmon Resonance Enhancer for Direct and Ultrasensitive Detection of Exosomes.

Surface plasmon resonance (SPR) spectroscopy with non-labelling, sensitive, and real-time properties is critical for clinical diagnosis applications. However, conventional SPR sensors face the challenge of lower sensitivity and selectivity for trace exosomes assay in complex serum. We proposed a core-shell Au@SiO2-Au film (Au@SiO2-Au film) metasurface to enhance SPR signal based on systematic study on the relationship between gap modes and SPR enhancement. The self-assembled multifunctional peptide was designed as recognition layer with antifouling properties for ultrasensitive and selective detection of PD-L1+ exosomes in serum. The tuning electromagnetic (EM) field model by manipulating the gap was established to guide the preparation of Au@SiO2-Au film metasurface. The in-plane and out-of-plane coupling of Au@SiO2 nanoparticles (NPs) could greatly enlarge and enhance three-dimensional EM field to meet the size of exosomes located in the evanescent field. At the structural level, we achieved high sensitivity (0.16 particles/mL) and a broad response range (10-5 × 103 particles/mL) through optimizing the thickness of SiO2 and surface coverage of Au@SiO2. Furthermore, clinical sample assay achieved the optimal diagnostic accuracy (AUC = 0.97) for differentiating cancer patients from healthy controls. This work provides an opportunity for the construction of a tunable gap mode as SPR enhancer in a total internal reflection architecture. The systematic study on the relationship between gap modes and SPR sensitivity provides a broad scope for promoting direct, efficient, highly selective, and sensitive detection of SPR sensors for clinical application.

Dobutamine-induced alternations in cerebral blood flow of healthy adults: a 3D pseudocontinuous arterial spin labeling study.

BACKGROUND: It is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics. METHODS: Forty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes. RESULTS: HR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P < 0.001, pixel level P < 0.05). Logistic regression showed that body mass index (BMI; odds ratio [OR] 5.80, 95% confidence interval [CI] 1.60-21.01, P = 0.008], resting SBP (OR 0.64, 95% CI 0.45-0.92, P = 0.014), and BA diameter (OR 11.04, 95% CI 1.05-116.53, P = 0.046) were significantly associated with frontal lobe CBF changes. CONCLUSIONS: Dobutamine-induced stress significantly decreased CBF in the frontal lobe anterior circulation. Individuals with a high BMI and low SBP during the dobutamine stress test are more likely to have a stress-induced CBF decrease. Thus, attention should be paid to blood pressure, BMI, and cerebrovascular morphology of patients undergoing dobutamine stress echocardiography or those receiving intensive care or anesthesia.

COR27 and COR28 Are Novel Regulators of the COP1-HY5 Regulatory Hub and Photomorphogenesis in Arabidopsis.

Plants have evolved sensitive signaling systems to fine-tune photomorphogenesis in response to changing light environments. Light and low temperatures are known to regulate the expression of the COLD REGULATED (COR) genes COR27 and COR28, which influence the circadian clock, freezing tolerance, and flowering time. Blue light stabilizes the COR27 and COR28 proteins, but the underlying mechanism is unknown. We therefore performed a yeast two-hybrid screen using COR27- and COR28 as bait and identified the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) as an interactor. COR27 and COR28 physically interact with COP1, which is in turn responsible for their degradation in the dark. Furthermore, COR27 and COR28 promote hypocotyl elongation and act as negative regulators of photomorphogenesis in Arabidopsis (Arabidopsis thaliana). Genome-wide gene expression analysis showed that HY5, COR27, and COR28 co-regulate many common genes. COR27 interacts directly with HY5 and associates with the promoters of the HY5 target genes HY5 and PIF4, then regulates their transcription together with HY5. Our results demonstrate that COR27 and COR28 act as key regulators in the COP1-HY5 regulatory hub, by regulating the transcription of HY5 target genes together with HY5 to ensure proper skotomorphogenic growth in the dark and photomorphogenic development in the light.

Phenotypic Heterogeneity in Patients with Mutations in the Mitochondrial Complex I Assembly Gene NDUFAF5.

BACKGROUND: Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome. OBJECTIVE: We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations. METHODS: Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts. RESULTS: Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient. CONCLUSIONS: The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Climatic and Economic Background Determine the Disparities in Urbanites' Expressed Happiness during the Summer Heat.

Climate-change-induced extreme weather events increase heat-related mortality and health risks for urbanites, which may also affect urbanites' expressed happiness (EH) and well-being. However, the links among EH, climate, and socioeconomic factors remain unclear. Here we collected ∼6 million geotagged tweets from 44 Chinese prefecture-level cities based on Sina Weibo and performed a quadratic regression model to explore the relationships between summer heat and EH. A three-stage analysis was developed to examine spatiotemporal heterogeneity and identify factors contributing to disparities in urbanites' EH. Results show that all cities exhibited a similar hump-shaped relationship, with an overall optimal temperature (OT) of 22.8 °C. The estimated OT varied geographically, with 25.3, 23.8, and 20.0 °C from north to south. Moreover, a 1 standard deviation increase in heatwave intensity was associated with a 0.813 (95% CI: 0.177, 1.449) standard deviation decrease in EH. Notably, within the geographic scope of this study, it was observed that urbanites in northern China and economically underdeveloped cities faced significantly lower heat risks during the summer heat. This research provides insight for future studies and practical applications concerning extreme weather events, urbanites' mental health, and sustainable urban development goal.

Can photoluminescence quenching be a predictor for perovskite solar cell efficiencies?

Bromide-based perovskites have large bandgaps, making them attractive for tandem solar cells developed to overcome the Shockley-Queisser limit. A perovskite solar cell architecture employs transporting layers to improve charge extraction and transport. Due to the wide variety of materials and preparation methods, it is critical to devise fast screening methods to rank transporting layers. Herein, we evaluate perovskite fluorescence quenching followed by time- and energy-resolved photoluminescence (TER-PL) and analyse the intensity dependence as a potential method to qualify charge-transporting layers rapidly. The capability of the technique was evaluated with TiO2/FAPbBr3 and SnO2/FAPbBr3, the most commonly used electron transporting layers, which were prepared using standard protocols to make best-performing devices. The results revealed that TiO2 is the most effective quencher due to the higher density of states in the conduction band, consistent with Marcus-Gerischer's theory. However, record-performance devices use SnO2 as the electron transport layer. This shows that the relationship between photoluminescence quenching and device performance is not bidirectional. Therefore, additional measurements like conductivity are also needed to provide reliable feedback for device performance.

Excited-state and charge-carrier dynamics in binary conjugated polymer dots towards efficient photocatalytic hydrogen evolution.

Aqueous dispersed conjugated polymer dots (Pdots) have shown promising application in photocatalytic hydrogen evolution. To efficiently extract photogenerated charges from type-II heterojunction Pdots for hydrogen evolution, the mechanistic study of photophysical processes is essential for Pdot optimization. Within this work, we use a PFODTBT donor (D) polymer and an ITIC small molecule acceptor (A) as a donor/acceptor (D/A) model system to study their excited states and charge/energy transfer dynamics via steady-state and time-resolved photoluminescence spectroscopy, respectively. Charge-carrier generation and the recombination dynamics of binary Pdots with different D/A ratios were followed using femtosecond transient absorption spectroscopy. A significant spectral relaxation of photoluminescence was observed for individual D Pdots, implying an energetic disorder by nature. However, this was not seen for charge carriers in binary Pdots, probably due to the ultrafast charge generation process at an early time (<200 fs). The results showed slower charge recombination upon increasing the ratio of ITIC in binary Pdots, which further resulted in an enhanced photocatalytic hydrogen evolution, twice that as compared to individual D Pdots. Although binary Pdots prepared via the nanoprecipitation method exhibit a large interfacial area that allows high charge generation efficiencies, it also provides a high possibility for charge recombination and limits the further utilization of free charges. Therefore, for the future design of type-II heterojunction Pdots, suppressing the charge carrier recombination via increasing the crystallinity and proper phase segregation is necessary for enhanced photocatalytic hydrogen evolution.

Does the quality of street greenspace matter? Examining the associations between multiple greenspace exposures and chronic health conditions of urban residents in a rapidly urbanising Chinese city.

BACKGROUND: Numerous studies have demonstrated that greenspace(GS) exposure is associated with health improvements in individuals with hypertension and diabetes. However, studies examining the associations between multiple GS exposures and chronic health conditions in developing countries are limited. METHODS: Geospatial data and spatial analysis were employed to objectively measure the total neighbourhood vegetative cover (mean value of normalised difference vegetation index [NDVI] within specific buffer zone) and proximity to park-based GS (network distance from home to the entrance of park-based GS). Street view imagery and machine learning techniques were used to measure the subjective perceptions of street GS quality. A multiple linear regression model was applied to examine the associations between multiple GS exposures and the prevalence of hypertension and diabetes in neighbourhoods located in Qingdao, China. RESULTS: The model explained 29.8% and 28.2% of the prevalence of hypertension and diabetes, respectively. The results suggested that: 1) the total vegetative cover of the neighbourhood was inversely correlated with the prevalence of hypertension (ß = -0.272, p = 0.013, 95% confidence interval (CI): [-1.332, -0.162]) and diabetes (ß = -0.230, p = 0.037, 95% CI: [-0.720, -0.008]). 2) The street GS quality was negatively correlated with the prevalence of hypertension (ß = -0.303, p = 0.007, 95% CI: [-2.981, -0.491]) and diabetes (ß = -0.309, p = 0.006, 95% CI: [-1.839, -0.314]). 3) Proximity to park-based GS and the prevalence of hypertension and diabetes mellitus were not significantly correlated. CONCLUSIONS: This study used subjective and objective methods to comprehensively assess the greenspace exposure from overhead to eye level, from quantity, proximity to quality. The results demonstrated the beneficial relationships between street GS quality, total vegetative cover, and chronic health in a rapidly urbanising Chinese city. Furthermore. the effect of street GS quality was more pronounced in potentially mitigating chronic health problems, and improving the quality of street GS might be an efficient and effective intervention pathway for addressing chronic health issues in densely populated cities.

Nexus between genome-wide copy number variations and autism spectrum disorder in Northeast Han Chinese population.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, with an increasing prevalence worldwide. Copy number variation (CNV), as one of genetic factors, is involved in ASD etiology. However, there exist substantial differences in terms of location and frequency of some CNVs in the general Asian population. Whole-genome studies of CNVs in Northeast Han Chinese samples are still lacking, necessitating our ongoing work to investigate the characteristics of CNVs in a Northeast Han Chinese population with clinically diagnosed ASD. METHODS: We performed a genome-wide CNVs screening in Northeast Han Chinese individuals with ASD using array-based comparative genomic hybridization. RESULTS: We found that 22 kinds of CNVs (6 deletions and 16 duplications) were potentially pathogenic. These CNVs were distributed in chromosome 1p36.33, 1p36.31, 1q42.13, 2p23.1-p22.3, 5p15.33, 5p15.33-p15.2, 7p22.3, 7p22.3-p22.2, 7q22.1-q22.2, 10q23.2-q23.31, 10q26.2-q26.3, 11p15.5, 11q25, 12p12.1-p11.23, 14q11.2, 15q13.3, 16p13.3, 16q21, 22q13.31-q13.33, and Xq12-q13.1. Additionally, we found 20 potential pathogenic genes of ASD in our population, including eight protein coding genes (six duplications [DRD4, HRAS, OPHN1, SHANK3, SLC6A3, and TSC2] and two deletions [CHRNA7 and PTEN]) and 12 microRNAs-coding genes (ten duplications [MIR202, MIR210, MIR3178, MIR339, MIR4516, MIR4717, MIR483, MIR675, MIR6821, and MIR940] and two deletions [MIR107 and MIR558]). CONCLUSION: We identified CNVs and genes implicated in ASD risks, conferring perception to further reveal ASD etiology.

Association between pyrethroid exposure and osteoarthritis: a national population-based cross-sectional study in the US.

BACKGROUND: With the restriction of organophosphorus and other insecticides, pyrethroids are currently the second most-used group of insecticides worldwide due to their advantages such as effectiveness and low toxicity for mammalian. Animal studies and clinical case reports have documented associations between adverse health outcomesand exposure to pyrethroids. At present, the association between chronic pyrethroid exposure and osteoarthritis (OA) remains elusive. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 and 2007-2014 were used to explore the associations of pyrethroid exposure and OA. Urinary level of 3-phenoxybenzoic acid (3-PBA) in urine samples was used to evaluate the exposure of pyrethroid, and OA was determined on the basis of self-reported physician diagnoses. Multivariable logistic regression models were used to investigate the association between pyrethroid exposure and OA. RESULTS: Among the 6528 participants, 650 had OA. The weighted geometric mean of urinary volume-based 3-PBA concentration were 0.45 µg/L. With adjustments for major confounders, compared to participants in the lowest quartile of urinary volume-based 3-PBA, those in the highest quartilehad higher odds of OA (odds ratio, 1.39; 95% confidence interval: 1.01, 1.92). There was no nonlinear relationship between urinary volume-based 3-PBA and OA (P for non-linearity = 0.89). CONCLUSION: High urinary 3-PBA concentration was associated with increased OA odds in the US adults. Pyrethroid exposure in the population should be monitored regularly.

Retrospective Analysis of the Clinical Features and Pregnancy Outcomes in 124 Pregnant Patients with Non-Obstetric Acute Abdomen.

Objective: To retrospectively analyze the clinical characteristics and pregnancy outcomes of patients with the non-obstetric acute abdomen (AAD) during pregnancy. Methods: A total of 124 patients with non-obstetric AAD during pregnancy were selected, including acute gastroenteritis (n = 42), acute appendicitis (n = 24), pedicle torsion of ovarian tumor (n = 21), acute pancreatitis (n = 10), urinary stones (n = 8), acute cholecystitis (n = 5), ruptured ovarian cyst (n = 6), red degeneration of hysteromyoma (n = 4), pedicle torsion of subserosal hysteromyoma (n = 3) and intestinal obstruction (n = 1). The clinical data of included patients were collected, and their clinical manifestations, clinical diagnosis, treatment modalities, and pregnancy outcomes were analyzed. Results: Common clinical manifestations included abdominal pain, nausea, vomiting, fever, elevated leukocytes, and neutrophil count. Clinical diagnosis analysis revealed acute gastroenteritis (n = 42), acute appendicitis (n = 24), pedicle torsion of ovarian tumor (n = 21), acute pancreatitis (n = 10), urinary stones (n = 8), acute cholecystitis (n = 5), ruptured ovarian cyst (n = 6), red degeneration of hysteromyoma (n = 4), pedicle torsion of subserosal hysteromyoma (n = 3) and intestinal obstruction (n = 1) in patients. Surgery was performed for conditions such as acute appendicitis and ovarian tumor torsion, while conservative treatment was preferred for cases of acute gastroenteritis. 65 patients received surgery and 59 patients received conservative treatment. The pregnancy outcomes indicated 113 patients with full-term delivery, 5 with premature delivery, 6 with miscarriage and 1 with fetal death. Pregnancy outcomes varied, with 113 patients achieving full-term delivery, 5 experiencing premature delivery, 6 undergoing miscarriage, and 1 case of fetal death. Conclusion: Non-obstetric AAD during pregnancy manifests clinically as nausea and vomiting, abdominal pain, elevated body temperature, and leukocytes, all of which have pregnancy outcomes. Pregnant patients with non-obstetric AAD should be diagnosed according to their clinical manifestations, physical examinations, and relevant imaging examinations, and appropriate treatment modalities should be selected to achieve a better pregnancy outcome and ensure the safety of the mother and baby during the clinical diagnosis and treatment process. This study underscores the need for prompt and accurate diagnosis in pregnant patients with non-obstetric AAD, to optimize pregnancy outcomes and ensure maternal-fetal safety.

Benzothiazole-Propanamide Linker Pyrrolidine (Morpholine) as Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors.

According to the fusion technique create effective multi-target-directed ligands, in this study, we designed and synthesized a series of benzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl) or 3-(morph- olino-1-yl)propanamide derivatives, and evaluated their inhibitory potency against MAOs, AChE, BuChE by in vitro enzyme effect assays. Based on activity results, we found that derivatives N-(5-methylbenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 c) and N-(6-bromobenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 h) showed good inhibitory potency against BuChE with IC50 values of 15.12 µM and 12.33 µM, respectively. Besides, 2 c and 2 h also exhibited selective MAO-B inhibitory effects with inhibition rates of 60.10 % and 66.30 % at 100 µM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100 µM. The toxicity analysis in vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100 µM. Molecular modeling studies showed that 2 c and 2 h could bind to the active site of BuChE. This research paves the way for further study aimed at designing MAO-B and BuChE inhibitors for the treatment of neurodegenerative disorders.

A Multi-Step Fusion Network for Semantic Segmentation of High-Resolution Aerial Images.

The demand for semantic segmentation of ultra-high-resolution remote sensing images is becoming increasingly stronger in various fields, posing a great challenge with concern to the accuracy requirement. Most of the existing methods process ultra-high-resolution images using downsampling or cropping, but using this approach could result in a decline in the accuracy of segmenting data, as it may cause the omission of local details or global contextual information. Some scholars have proposed the two-branch structure, but the noise introduced by the global image will interfere with the result of semantic segmentation and reduce the segmentation accuracy. Therefore, we propose a model that can achieve ultra-high-precision semantic segmentation. The model consists of a local branch, a surrounding branch, and a global branch. To achieve high precision, the model is designed with a two-level fusion mechanism. The high-resolution fine structures are captured through the local and surrounding branches in the low-level fusion process, and the global contextual information is captured from downsampled inputs in the high-level fusion process. We conducted extensive experiments and analyses using the Potsdam and Vaihingen datasets of the ISPRS. The results show that our model has extremely high precision.