Rapid detection of colored and colorless macro- and micro-plastics in complex environment via near-infrared spectroscopy and machine learning.

To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.

Nivel de cumplimiento de metas internacionales de seguridad en un Sanatorio privado 2023 / Level of compliance with international safety goals in a private Sanatorium 2023

La presente investigación pretende evaluar el nivel de cumplimiento de las metas internacionales, que representan el foco principal para la mejora de calidad y seguridad de atención de los pacientes. La seguridad del paciente involucra a todos los estudios, prácticas y acciones promovidas por las instituciones sanitarias para disminuir y eliminar los riesgos de daños innecesarios relacionados con el cuidado de la salud. Metodología: Estudio descriptivo, observacional y transversal. De fuentes primaria y secundaria, Resultados: se abordaron las metas N° 1 la cual consiste en Identificar a los pacientes correctamente y la meta N° 6 la cual se refiere a Reducir el riesgo de lesiones en pacientes como resultado de caídas. En primer lugar, se destaca el cumplimiento en la identificación correcta del paciente y en segunda instancia la mejora del cumplimiento de medidas de prevención de caídas. Conclusión: Esta proximidad de los valores obtenidos genera un aspecto positivo para mejorar la seguridad de los pacientes y que, si bien el cumplimiento de las metas no es el deseado, es cercano al porcentaje planteado. Lo que en definitiva hace a este estudio un antecedente importante en la mejora continua con vista al futuro cercano[AU]

This research aims to evaluate the level of compliance with international goals, which represent the main focus for improving the quality and safety of patient care. Patient safety involves all studies, practices and actions promoted by health institutions to reduce and eliminate the risks of unnecessary harm related to health care. Methodology: Descriptive, observational and transversal study. From primary and secondary sources, Results: goals No. 1 were addressed, which consists of Identifying patients correctly and goal No. 6, which refers to Reducing the risk of injuries in patients as a result of falls. Firstly, compliance with correct patient identification stands out and secondly, improvement in compliance with fall prevention measures. Conclusion: This proximity of the values obtained generates a positive aspect to improve patient safety and that, although the fulfillment of the goals is not as desired, it is close to the proposed percentage. Which ultimately makes this study an important precedent in continuous improvement for the near future[AU]

Esta pesquisa tem como objetivo avaliar o nível de cumprimento das metas internacionais, que representam o foco principal para a melhoria da qualidade e segurança do atendimento ao paciente. A segurança do paciente envolve todos os estudos, e ações promovidas pelas instituições de saúde para reduzir e eliminar os riscos de danos desnecessários relacionados à assistência à saúde. Metodologia: Estudo descritivo, observacional e transversal. De fontes primárias e secundárias, dependendo do indicador e do objetivo para o qual a medição está sendo realizada. Resultados: Nesta pesquisa serão abordadas as metas nº1, que consiste em Identificar corretamente os pacientes e a meta nº 6, que es Reduzir o risco de lesões nos pacientes em decorrência de quedas. Foi realizado nos dois locais. Em primeiro lugar, destaca-se o cumprimento da correta identificação do paciente e, em segundo lugar, a melhoria no cumprimento das medidas de prevenção de quedas. Conclusão: Essa proximidade dos valores obtidos gera um aspecto positivo para melhorar a segurança do paciente e que, embora o cumprimento das metas não seja o desejado, está próximo do percentual proposto. O que acaba por tornar este estudo um precedente importante na melhoria contínua com vista ao futuro próximo.

Characterization of atmospheric nitroaromatic compounds in Southwest China by direct injection liquid chromatography-tandem mass spectrometry analysis of aerosol extracts.

Nitroaromatic compounds (NACs) in ambient particles are of great concern due to their adverse effects on human health and climate. However, investigations on the characteristics and potential sources of NACs in Southwest China are still scarce. In this study, a field sampling campaign was carried out in the winter of 2022 at a suburban site in Mianyang, Southwest China. A direct injection liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to rapidly determine 10 NACs in fine particulate matter (PM2.5) extracts. The method was sensitive for the quantification of the NACs, with a limit of quantification (LOQ) in the range of 0.092-0.52 ng mL-1. Then, the developed method was applied to determine the concentrations of nitrophenols (NPs), nitrocatechols (NCs), nitrosalicylic acids (NSAs), and nitronaphthol in PM2.5 in Mianyang. The average concentration of total NACs was 78.2 ± 31.2 ng m-3, with daily concentrations ranging from 20.7 to 127.9 ng m-3. Among the measured NACs, 4-nitrocatechol was the most abundant, accounting for 57.8% of the NACs in winter. The five NPs compounds together contributed to 14% of the NACs, which was lower than in other Chinese cities due to the warm climate in winter in Southwest China. NSAs and nitronaphthol each accounted for less than 5% of the NACs. Three major sources of NACs were identified based on the principal component analysis, including vehicle emissions, biomass burning, and secondary formation. The significant correlation between individual NACs and NO2 supported their secondary formation sources. The good correlation between NPs and cloud amount further suggested that gas-phase oxidation was the possible NPs formation mechanism. Our findings revealed the important role of nitrocatechols in NACs in Southwest China, implying that more measures should be taken to control biomass burning and aromatic volatile organic compounds emissions to reduce the level of NACs.

Prediction of disease progression in individuals with subjective cognitive decline using brain network analysis.

OBJECTIVE: The objective of this study is to explore potential differences in brain functional networks at baseline between individuals with progressive subjective cognitive decline (P-SCD) and stable subjective cognitive decline (S-SCD), as well as to identify potential indicators that can effectively distinguish between P-SCD and S-SCD. METHODS: Alzheimer's Disease Neuroimaging Initiative (ADNI) database was utilized to enroll SCD individuals with a follow-up period of over 3 years. This study included 39 individuals with S-SCD, 15 individuals with P-SCD, and 45 cognitively normal (CN) individuals. Brain functional networks were constructed based on the AAL template, and graph theory analysis was performed to determine the topological properties. RESULTS: For global metric, the S-SCD group exhibited stronger small-worldness with reduced connectivity among nearby nodes and accelerated compensatory information transfer capacity. For nodal efficiency, the S-SCD group showed increased connectivity in bilateral posterior cingulate gyri (PCG). However, for nodal local efficiency, the P-SCD group exhibited significantly reduced connectivity in the right cerebellar Crus I compared with the S-SCD group. CONCLUSION: There are differences in brain functional networks at baseline between P-SCD and S-SCD groups. Furthermore, the right cerebellar Crus I region may be a potentially useful brain area to distinguish between P-SCD and S-SCD.

Directly selecting cell-type marker genes for single-cell clustering analyses.

In single-cell RNA sequencing (scRNA-seq) studies, cell types and their marker genes are often identified by clustering and differentially expressed gene (DEG) analysis. A common practice is to select genes using surrogate criteria such as variance and deviance, then cluster them using selected genes and detect markers by DEG analysis assuming known cell types. The surrogate criteria can miss important genes or select unimportant genes, while DEG analysis has the selection-bias problem. We present Festem, a statistical method for the direct selection of cell-type markers for downstream clustering. Festem distinguishes marker genes with heterogeneous distribution across cells that are cluster informative. Simulation and scRNA-seq applications demonstrate that Festem can sensitively select markers with high precision and enables the identification of cell types often missed by other methods. In a large intrahepatic cholangiocarcinoma dataset, we identify diverse CD8+ T cell types and potential prognostic marker genes.

The Influence of Lactobacillus spp. Secondary Metabolites Isolated from Immature Egyptian Honey on Human Pathogens, Transcription of Virulence Genes and Lung Cancer.

This work aimed to isolate, and identify Lactic Acid Bacteria LAB from Egyptian immature citrus honey, and characterize their secondary metabolites, as well as determine the antibacterial activities and transcription of virulence genes (stx1, stx2, and eae) influenced by these bacterial secondary metabolites. From twenty hives, twenty immature citrus bee honey samples were taken. Traditional cultural and biochemical testing were used, followed by molecular confirmation. Further, LAB isolates' antibacterial and cytotoxic properties were investigated. 16S rRNA gene sequencing were assessed and, two lactic acid bacterial isolates were identified as Lactobacillus acidophilus Ch2 and Levilactobacillus brevis Ch1. Both isolates have good antagonistic action against clinical pathogens, with Levilactobacillus brevis Ch1 exhibiting the best antibacterial activity against all indicator pathogens examined. When compared to untreated cancer cells, the isolates demonstrated significant cytotoxic activity. Ch1 and Ch2 cell viability percentages were 39.5% and 18.76%, respectively. Furthermore, when exposed to Levilactobacillus brevis Ch1 metabolites, Shiga-producing Escherichia coli (STEC) virulence gene expression was suppressed. To identify bacterial secondary metabolites, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) approach was developed. Twenty-seven metabolites from diverse chemical classes were discovered in the crude extracts with antibacterial and anticancer characteristics. This is the first thorough investigation on the metabolic profile of LAB isolated from immature Egyptian honey and the findings suggested that isolates or their secondary metabolites could be used in the food sector as medicinal alternatives or as a biocontrol agent.

Assessing the dynamics and trigger factors of drought propagation in the China-Pakistan economic corridor: A three-dimensional perspective.

Effectively managing drought in the China-Pakistan Economic Corridor (CPEC) region requires a precise understanding of the three-dimensional characteristics of meteorological drought (MD) and agricultural drought (AD), as well as the factors that trigger their propagation. This study employed non-stationary drought indices (NSPEI and SSMI) to develop a cutting-edge 3-dimensional drought identification model. This model was used to detect MD and AD patterns from 1981 to 2022 in the CPEC region and was integrated with binomial logistic regression to identify the critical factors that drive drought propagation. This study's key findings include: 1) Between 1981 and 2022, droughts in Xinjiang, China, exhibited a discernible southward migration trend, while in Pakistan, droughts showed a northward migration pattern. Drought frequency and extent have increased over time, with affected regions becoming more widespread in CPEC. Notably, drought events with higher preceding drought contagion indices (DCI) were more likely to evolve into extreme, long-term droughts. 2) Drought area emerged as a significant positive triggering factor for drought propagation in the CPEC region. Conversely, snowmelt in Xinjiang and the leaf area index for low vegetation in Pakistan acted as triggering elements affecting negatively. 3) Various factors played a pivotal role during drought propagation process, including geographical coordinates of drought centroids, DCI, and temperature variations. Additionally, snowmelt and snow evaporation significantly impacted drought propagation in Xinjiang, while vegetation cover in Pakistan played a crucial role during the drought propagation process. By utilizing four regression models and conducting comprehensive attribution analysis, this study sheds light on the characteristics of drought propagation and the factors influencing it. These findings are valuable for enhancing early warning systems and implementing effective drought mitigation strategies in the CPEC region.

Three new compounds from the fruits of Solanum virginianum L. and their anti-inflammatory activities.

Three new compounds 1-glyceryl 9(ß), 10(α), 11(ß)-trihydroxy-12(Z)-octadecenoate, 2'S-20-O-p-hydroxyphenylpropionyloxy-20-hyd-roxyarachidic acid glycerol ester (2), 3-O-α-l-arabinopyranosyl-(1→6)-ß-d-glucopyranoside of ethyl (3S)-hydroxybutanoate (3), as well as a new natural product (4) were isolated from the fruits of Solanum virginianum L. The structures of 26 compounds were determined by comprehensive spectroscopic analyses, NMR calculation, chemical methods, and comparisons of spectroscopic data. Compounds 2 and 16 exhibited good anti-inflammatory activity in the LPS-induced RAW 264.7 inflammatory model with IC50 values of 16.75 ± 1.54 and 22.43 ± 2.01 µM, respectively.

Isolation and identification of primary cells: A comprehensive primary cell culture experiment for graduate students.

Experimental teaching is an important part of postgraduate training in basic and clinical medicine. While primary cell isolation and identification are among the most important research techniques for medical graduate students, most graduate students do not understand and master these techniques before starting their research experience. In particular, many students lack training in this field, and high-quality teaching and learning materials are still very sparse. Here, we designed a practical experiment course for graduate students engaged in research. The target students usually have research projects involving primary cell culture in their future research, making the course highly applicable for the students. The lab exercise focused on the methods of primary cell isolation (including mechanical grinding method, explant culture method and enzymatic digestion method) and identification (including flow cytometry, immunofluorescence, and periodic acid-Schiff (PAS) staining). It aimed to help students master the conceptual, principle, technical, operation, and analytical skills related to primary cell culture and contributed to their foundation for future research. Students generally reflect that they have initially mastered the isolation and identification of primary cell culture as a result of the course. Student feedback also indicates significantly increased confidence in the practical application of primary cell culture in the future. Here, we provide our experience for others who may want to implement similar courses.

CANTATAdb 3.0: an updated repository of plant long noncoding RNAs.

CANTATAdb 3.0 is an updated database of plant long non-coding RNAs (lncRNAs), containing 571,688 lncRNAs identified across 108 species, including 100 Magnoliopsida (flowering plants), a significant expansion from the previous version. A notable feature is the inclusion of 112,980 lncRNAs that are expressed specifically in certain plant organs or embryos, indicating their potential role in development and organ-specific processes. In addition, CANTATAdb 3.0 includes 74,886 pairs of evolutionarily conserved lncRNAs found across 47 species and inferred from genome-genome alignments as well as conserved lncRNAs obtained with a similarity-search approach in 5,479 species pairs, which would further aid in the selection of lncRNAs for functional studies. Interestingly, we find that conserved lncRNAs with tissue specific expression patterns tend to occupy the same plant organ across different species, pointing toward conserved biological roles. The database now offers extended search capabilities, and downloadable data in popular formats, further facilitating research on plant lncRNAs.

Are Gender Identities and Gender Ideologies Associated with the Variety and Type of Owned Sex Toys? Evidence from a Large Italian Sample of Cisgender Individuals.

Research on the use of sex toys has been primarily performed from a medical perspective, while there is still limited research from a psychosocial perspective. To bridge this gap, in this study we examined whether some psychosocial variables might be linked to sex toy ownership in a sample of 3960 Italian (cisgender men and women) sex toy buyers. More specifically, we investigated the association between gender identities and ideologies and the variety and types of sex toys owned. Based on the data, we detected two dimensions underlying the ownership of sex toys: (1) orientation to owning kinky sex toys and (2) orientation to owning clit-oriented sex toys. Results showed that benevolent sexism and gender system justification were negatively correlated with owning clit-oriented toys. Moreover, strongly gender-identified participants owned a small variety of different toys and preferred toys that were designed to stimulate the vagina or clitoris over less commonly-used toys. No significant correlation between feminist identification and sex toy type owned was found when gender identification was taken into account. These results suggest that the owning of sex toys might be associated with traditional gender ideology and the strength of gender identification.

Head poses and grimaces: Challenges for automated face identification algorithms?

In today's biometric and commercial settings, state-of-the-art image processing relies solely on artificial intelligence and machine learning which provides a high level of accuracy. However, these principles are deeply rooted in abstract, complex "black-box systems". When applied to forensic image identification, concerns about transparency and accountability emerge. This study explores the impact of two challenging factors in automated facial identification: facial expressions and head poses. The sample comprised 3D faces with nine prototype expressions, collected from 41 participants (13 males, 28 females) of European descent aged 19.96 to 50.89 years. Pre-processing involved converting 3D models to 2D color images (256 × 256 px). Probes included a set of 9 images per individual with head poses varying by 5° in both left-to-right (yaw) and up-and-down (pitch) directions for neutral expressions. A second set of 3,610 images per individual covered viewpoints in 5° increments from -45° to 45° for head movements and different facial expressions, forming the targets. Pair-wise comparisons using ArcFace, a state-of-the-art face identification algorithm yielded 54,615,690 dissimilarity scores. Results indicate that minor head deviations in probes have minimal impact. However, the performance diminished as targets deviated from the frontal position. Right-to-left movements were less influential than up and down, with downward pitch showing less impact than upward movements. The lowest accuracy was for upward pitch at 45°. Dissimilarity scores were consistently higher for males than for females across all studied factors. The performance particularly diverged in upward movements, starting at 15°. Among tested facial expressions, happiness and contempt performed best, while disgust exhibited the lowest AUC values.

Notes on the Pselaphodes Westwood complex (Coleoptera, Staphylinidae, Pselaphinae) of Hubei, China, with description of a new species and additional faunistic data.

The Pselaphodes Westwood complex of genera is represented in Hubei Province by four genera and eight species. Recent field work at Wanchaoshan Nature Reserve, Xingshan County revealed a small series of material belonging to this complex. In this paper, we describe Pselaphodeswanchaoshanus sp. nov. and provide new faunistic data for P.nomurai Yin, Li & Zhao. A key to the hitherto known members of Pselaphodes complex that occur in Hubei is provided to facilitate ready species identification.

Four genera of the subfamily Opiinae Blanchard (Hymenoptera, Braconidae) new for Japan, with the description of two new species.

Four genera are reported for the first time from Japan (Areotetes van Achterberg & Li, 2013, Indiopius Fischer, 1966, Neopius Gahan, 1917 and Sternaulopius Fischer, 1965), and keys are provided for the species of these genera. Two new species are described and illustrated: Areotetesconvergens sp. nov. and Sternaulopiusmaculiferus sp. nov.

Occurrence, accumulation, ecological risk, and source identification of potentially toxic elements in multimedia in a subtropical bay, Southeast China.

Potentially toxic elements (PTEs) in seawater and sediments may be amplified along the aquatic food chain, posing a health threat to humans. This study comprehensively analyzed the concentrations, distribution, potential sources, and health risk of 7 PTEs in multimedia (seawater, sediment and organism) in typical subtropical bays in southern China. The results indicated that Zn was the most abundant element in seawater, and the average concentration of Cd in sediment was 3.93 times higher than the background value. Except for As, the seasonal differences in surface seawater were not significant. The content of Zn in fishes, crustacea, and shellfish was the highest, while the contents of Hg and Cd were relatively low. Bioaccumulation factor indicated that Zn was a strongly bioaccumulated element in seawater, while Cd was more highly enriched by aquatic organisms in sediment. According to principal component analysis (PCA), and positive matrix factorization (PMF), the main sources of PTEs in Quanzhou Bay were of natural derivation, industrial sewage discharge, and agricultural inputs, each contributing 40.4 %, 24.2 %, and 35.4 %, respectively. This study provides fundamental and significant information for the prevention of PTEs contamination in subtropical bays, the promotion of ecological safety, and the assessment of human health risk from PTEs in seafood.

Flow dynamics and turbulent coherent structures around sediment reduction plates of a sewer system.

In the management of urban drainage networks, great interest has been generated in the removal of sediments from sewer systems. The unsteady three-dimensional (3D) flow and turbulent coherent structures surrounding sediment reduction plates in a sewer system are investigated by means of the detached-eddy simulation (DES). Particular emphasis is given to detailing the instantaneous velocity and vorticity fields within the grooves, along with an examination of the three-dimensional, long-term, average flow structure at a Reynolds number of approximately 105. Velocity vectors demonstrate continuous flapping of the flow on the groove wall, periodically interacting with ejections of positive and negative vorticity originating from the grooves. The interaction between the three-dimensional groove flow and the shear flow leads to the downstream transport of patches of positive and negative vorticity, which significantly influence sediment transport. The high-velocity shear flows and strong vortices generated in undulating topography, as identified by the Q-criteria, are the key factors contributing to the efficient sediment reduction capabilities of the sediment reduction plates. The sediment reduction plates with partially enclosed structures exhibit low sedimentation rates in grooves on the plate, a broader acceleration region, and a lesser impact on the flow capacity. The results improve the understanding of the hydrodynamics and turbulent coherent structures surrounding the sediment reduction plates while elucidating the driving factors behind the enhancement of sediment scouring and suspension capacities. These results indicate that the redesign of the plates as partially enclosed structures contributes to further improving their sediment reduction performance.

Characterization of biomass burning tracers in particulate matter at 12 sites in China: Significant increase of coal combustion emitted levoglucosan in northern China during winter.

Biomass burning (BB) is the largest contributor to carbonaceous aerosols globally. Specific organic tracers can track BB particles and identify BB types. At present, there is limited information on the composition of BB tracers on a continental scale. In this study, we conducted year-round sampling of particulate matter (PM) at 12 sites in China. Nine BB tracers were measured in PM with aerodynamic diameters <1.1 µm (PM<1.1), in the range of 1.1-3.3 µm (PM1.1-3.3), and > 3.3 µm (PM>3.3). The annual average concentration of these nine BB tracers (∑9 BB tracers) in the total PM was 366 ng m-3 with the majority of levoglucosan (66 %). The concentration of ∑9 BB tracers was higher in northern China than in southern China, especially in winter. ∑9 BB tracers were most enriched in PM<1.1 (50-61 % in mass), followed by PM1.1-3.3 and PM>3.3. The highest concentrations of ∑9 BB tracers were observed in winter, while satellite-recorded fire spots were intensive in autumn and spring. The mismatch of seasonal trends between them indicated that the high levels of BB tracers in winter was not due to open BB. The composition of 4-hydroxybenzoic acid, syringic acid and vanillic acid suggested that the burning of crop residues and softwoods were the major BB types in China. The ratio of levoglucosan to mannosan could neither identify the major BB types in China nor distinguish between BB and coal combustion. Correlation analysis and the PMF model demonstrated that non-BB sources contributed 7 %-58 % to levoglucosan at the 12 sites, with coal combustion being the predominant non-BB source in China, especially in northern urban sites during winter. Our findings suggest that caution should be taken in application of these organic tracers to identify BB types and estimate BB aerosols.

The role of ureteric indocyanine green fluorescence in colorectal surgery: a retrospective cohort study.

BACKGROUND: Ureteric injury (UI) is an infrequent but serious complication of colorectal surgery. Prophylactic ureteric stenting is employed to avoid UI, yet its efficacy remains debated. Intraoperative indocyanine green fluorescence imaging (ICG-FI) has been used to facilitate ureter detection. This study aimed to investigate the role of ICG-FI in identification of ureters during colorectal surgery and its impact on the incidence of UI. METHODS: A retrospective cohort study involving 556 consecutive patients who underwent colorectal surgery between 2018 and 2023 assessed the utility of routine prophylactic ureteric stenting with adjunctive ICG-FI. Patients with ICG-FI were compared to those without ICG-FI. Demographic data, operative details, and postoperative morbidity were analyzed. Statistical analysis included univariable regression. RESULTS: Ureteric ICG-FI was used in 312 (56.1%) patients, whereas 43.9% were controls. Both groups were comparable in terms of demographics except for a higher prevalence of prior abdominal surgeries in the ICG-FI group. Although intraoperative visualization was significantly higher in the ICG-FI group (95.3% vs 89.1%; p = 0.011), the incidence of UI was similar between groups (0.3% vs 0.8%; p = 0.585). Postoperative complications were similar between the two groups. Median stent insertion time was longer in the ICG-FI group (32 vs 25 min; p = 0.001). CONCLUSION: Ureteric ICG-FI improved intraoperative visualization of the ureters but was not associated with a reduced UI rate. Median stent insertion time increased with use of ureteric ICG-FI, but total operative time did not. Despite its limitations, this study is the largest of its kind suggesting that ureteric ICG-FI may be a valuable adjunct to facilitate  ureteric visualization during colorectal surgery.

Comprehensive source identification of heavy metals in atmospheric particulate matter in a megacity: A case study of Hangzhou.

Megacities face significant pollution challenges, particularly the elevated levels of heavy metals (HMs) in particulate matter (PM). Despite the advent of interdisciplinary and advanced methods for HM source analysis, integrating and applying these approaches to identify HM sources in PM remains a hurdle. This study employs a year-long daily sampling dataset for PM1 and PM1-10 to examine the patterns of HM concentrations under hazy, clean, and rainy conditions in Hangzhou City, aiming to pinpoint the primary sources of HMs in PM. Contrary to other HMs that remained within acceptable limits, the annual average concentrations of Cd and Ni were found to be 20.6 ± 13.6 and 46.9 ± 34.8 ng/m³, respectively, surpassing the World Health Organization's limits by 4.1 and 1.9 times. Remarkably, Cd levels decreased on hazy days, whereas Ni levels were observed to rise on rainy days. Using principal component analysis (PCA), enrichment factor (EF), and backward trajectory analysis, Fe, Mn, Cu, and Zn were determined to be primarily derived from traffic emissions, and there was an interaction between remote migration and local emissions in haze weather. Isotope analysis reveals that Pb concentrations in the Hangzhou region were primarily influenced by emissions from unleaded gasoline, coal combustion, and municipal solid waste incineration, with additional impact from long-range transport; it also highlights nuanced differences between PM1 and PM1-10. Pb isotope and PCA analyses indicate that Ni primarily stemmed from waste incineration emissions. This explanation accounts for the observed higher Ni concentrations on rainy days. Backward trajectory cluster analysis revealed that southern airflows were the primary source of high Cd concentrations on clean days in Hangzhou City. This study employs a multifaceted approach and cross-validation to successfully delineate the sources of HMs in Hangzhou's PM. It offers a methodology for the precise and reliable analysis of complex HM sources in megacity PM.

Discovery of Unprecedented Human Stercobilin Conjugates.

Two unique metabolites (M18 & M19) were detected in feces of human volunteers dosed orally with [14C]inavolisib with a molecular ion of parent plus 304 Da. They were generated in vitro by incubation with fecal homogenates and we have evidence that they are formed chemically and possibly enzymatically. Structural elucidation by high resolution mass spectrometry and NMR spectroscopy showed that the imidazole ring of inavolisib was covalently bound to partial structures derived from stercobilin, an end-product of heme catabolism produced by the gut microbiome. The structural difference between the two metabolites was the position of methyl and ethyl groups on the pyrrolidin-2-one moieties. We propose a mechanism of M18 and M19 generation from inavolisib and stercobilin whereby nucleophilic attack from the imidazole ring of inavolisib occurs to the bridging carbon of a stercobilin molecule. The proposed mechanism was supported by computational calculations of molecular orbitals and transition geometry. Significance Statement We report the characterization of two previously undescribed conjugates of the PI3K inhibitor inavolisib, generated by reaction with stercobilin, an end-product of heme catabolism produced by gut microbiome. These conjugates were confirmed by generating them using in vitro fecal homogenate incubation via non-enzymatic and possibly enzymatic reactions. Given the unique nature of the conjugate, it is plausible that it may have been overlooked with other small molecule drugs in prior studies.