Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.

PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation.

Eukaryotic elongation factor 2 (eEF2) mediates translocation of peptidyl-tRNA from the ribosomal A site to the P site to promote translational elongation. Its phosphorylation on Thr56 by its single known kinase eEF2K inactivates it and inhibits translational elongation. Extensive studies have revealed that different signal cascades modulate eEF2K activity, but whether additional factors regulate phosphorylation of eEF2 remains unclear. Here, we find that the X chromosome-linked intellectual disability protein polyglutamine-binding protein 1 (PQBP1) specifically binds to non-phosphorylated eEF2 and suppresses eEF2K-mediated phosphorylation at Thr56. Loss of PQBP1 significantly reduces general protein synthesis by suppressing translational elongation. Moreover, we show that PQBP1 regulates hippocampal metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) and mGluR-LTD-associated behaviors by suppressing eEF2K-mediated phosphorylation. Our results identify PQBP1 as a novel regulator in translational elongation and mGluR-LTD, and this newly revealed regulator in the eEF2K/eEF2 pathway is also an excellent therapeutic target for various disease conditions, such as neural diseases, virus infection, and cancer.

Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids.

Spinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the µ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCß3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analgesia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization.

EphB2-dependent prefrontal cortex activation promotes long-range social approach and partner responsiveness.

Social behavior starts with dynamic approach prior to the final consummation. The flexible processes ensure mutual feedback across social brains to transmit signals. However, how the brain responds to the initial social stimuli precisely to elicit timed behaviors remains elusive. Here, by using real-time calcium recording, we identify the abnormalities of EphB2 mutant with autism-associated Q858X mutation in processing long-range approach and accurate activity of prefrontal cortex (dmPFC). The EphB2-dependent dmPFC activation precedes the behavioral onset and is actively associated with subsequent social action with the partner. Furthermore, we find that partner dmPFC activity is responsive coordinately to the approaching WT mouse rather than Q858X mutant mouse, and the social defects caused by the mutation are rescued by synchro-optogenetic activation in dmPFC of paired social partners. These results thus reveal that EphB2 sustains neuronal activation in the dmPFC that is essential for the proactive modulation of social approach to initial social interaction.

Self-assembled soft alloy with Frank-Kasper phases beyond metals.

Soft building blocks, such as micelles, cells or soap bubbles, tend to adopt near-spherical geometry when densely packed together. As a result, their packing structures do not extend beyond those discovered in metallic glasses, quasicrystals and crystals. Here we report the emergence of two Frank-Kasper phases from the self-assembly of five-fold symmetric molecular pentagons. The µ phase, an important intermediate in superalloys, is indexed in soft matter, whereas the ϕ phase exhibits a structure distinct from known Frank-Kasper phases in metallic systems. We find a broad size and shape distribution of self-assembled mesoatoms formed by molecular pentagons while approaching equilibrium that contribute to the unique packing structures. This work provides insight into the manipulation of soft building blocks that deviate from the typical spherical geometry and opens avenues for the fabrication of 'soft alloy' structures that were previously unattainable in metal alloys.

High-Throughput Identification of Single Nanoparticles via Electrochemically Assisted High-Resolution Plasmonic Scattering Interferometric Microscopy.

The identification of nanoparticles within heterogeneous mixtures poses significant challenges due to the similarity in physical properties among different nanomaterials. Here, we present electrochemically assisted high-resolution plasmonic scattering interferometric microscopy (HR-PSIM). This technique allows for the high-throughput identification of nanoparticles by accurately measuring the refractive index of individual nanoparticles without interference from background signals. Through elimination of parabolic scattering interference and employing electrochemical modulation, HR-PSIM demonstrates high spatial resolution and stability against background noise, enabling the differentiation of nanoparticles with closely matched refractive indices, such as Au and Ag nanoparticles. The efficacy of this method is demonstrated through its application in real-time, label-free imaging of nanoparticle electrochemical activity, providing a platform for the precise and high-throughput characterization of nanomaterials. The robustness of our approach against electrochemical interference and its high spatial resolution mark a significant advancement in the field of nanomaterial analysis, promising wide-ranging applications in nanoparticle research and beyond.

Unraveling CCL20's role by regulating Th17 cell chemotaxis in experimental autoimmune prostatitis.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.

Whole-genome sequencing reveals genomic diversity and selection signatures in Xia'nan cattle.

BACKGROUND: The crossbreeding of specialized beef cattle breeds with Chinese indigenous cattle is a common method of genetic improvement. Xia'nan cattle, a crossbreed of Charolais and Nanyang cattle, is China's first specialized beef cattle breed with independent intellectual property rights. After more than two decades of selective breeding, Xia'nan cattle exhibit a robust physique, good environmental adaptability, good tolerance to coarse feed, and high meat production rates. This study analyzed the population genetic structure, genetic diversity, and genomic variations of Xia'nan cattle using whole-genome sequencing data from 30 Xia'nan cattle and 178 published cattle genomic data. RESULT: The ancestry estimating composition analysis showed that the ancestry proportions for Xia'nan cattle were mainly Charolais with a small amount of Nanyang cattle. Through the genetic diversity studies (nucleotide diversity and linkage disequilibrium decay), we found that the genomic diversity of Xia'nan cattle is higher than that of specialized beef cattle breeds in Europe but lower than that of Chinese native cattle. Then, we used four methods to detect genome candidate regions influencing the excellent traits of Xia'nan cattle. Among the detected results, 42 genes (θπ and CLR) and 131 genes (FST and XP-EHH) were detected by two different detection strategies. In addition, we found a region in BTA8 with strong selection signals. Finally, we conducted functional annotation on the detected genes and found that these genes may influence body development (NR6A1), meat quality traits (MCCC1), growth traits (WSCD1, TMEM68, MFN1, NCKAP5), and immunity (IL11RA, CNTFR, CCL27, SLAMF1, SLAMF7, NAA35, and GOLM1). CONCLUSION: We elucidated the genomic features and population structure of Xia'nan cattle and detected some selection signals in genomic regions potentially associated with crucial economic traits in Xia'nan cattle. This research provided a basis for further breeding improvements in Xia'nan cattle and served as a reference for genetic enhancements in other crossbreed cattle.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Quality appraisal and descriptive analysis of clinical practice guidelines for self-managed non-pharmacological interventions of cardiovascular diseases: a systematic review.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death around the world. Most CVDs-related death can be prevented by the optimal management of risk factors such as unhealthy diet and physical inactivity. Clinical practice guidelines (CPGs) for CVDs, provide some evidence-based recommendations which help healthcare professionals to achieve the best care for patients with CVDs. This systematic review aims to appraise the methodological quality of CPGs systematically and summarize the recommendations of self-managed non-pharmacological interventions for the prevention and management of CVDs provided by the selected guidelines. METHODS: A comprehensive electronic literature search was conducted via six databases (PubMed, Medline, The Cochrane Library, Embase, CINAHL, and Web of Science), seven professional heart association websites, and nine guideline repositories. The Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument was adopted to critically appraise the methodological quality of the selected guidelines. Content analysis was used to summarise recommended self-managed non-pharmacological interventions for CVDs. RESULTS: Twenty-three CPGs regarding different CVDs were included, in which four guidelines of CVDs, three for coronary heart diseases, seven for heart failure, two for atrial fibrillation, three for stroke, three for peripheral arterial disease, and one for hypertrophic cardiomyopathy. Twenty CPGs were appraised as high quality, and three CPGs as moderate quality. All twenty-three CPGs were recommended for use with or without modification. The domain of "Editorial Independence" had the highest standardized percentage (93.47%), whereas the domain of "Applicability" had the lowest mean domain score of 75.41%. The content analysis findings summarised some common self-managed non-pharmacological interventions, which include healthy diet, physical activity, smoking cessation, alcohol control, and weight management. Healthy diet and physical acidity are the most common and agreed on self-managed interventions for patients with CVDs. There are some inconsistencies identified in the details of recommended interventions, the intervention itself, the grade of recommendation, and the supported level of evidence. CONCLUSION: The majority of the summarized non-pharmacological interventions were strongly recommended with moderate to high-quality levels of evidence. Healthcare professionals and researchers can adopt the results of this review to design self-managed non-pharmacological interventions for patients with CVDs.

Neoadjuvant Chemotherapy or Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC. METHODS: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using Kaplan‒Meier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses. RESULTS: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001). CONCLUSION: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC.

On-chip integrated metasystem for spin-dependent multi-channel color holography.

On-chip integrated metasurface driven by in-plane guided waves is of great interests in various light-field manipulation applications such as colorful augmented reality and holographic display. However, it remains a challenge to design colorful multichannel holography by a single on-chip metasurface. Here we present metasurfaces integrated on top of a guided-wave photonic slab that achieves multi-channel colorful holographic light display. An end-to-end scheme is used to inverse design the metasurface for projecting off-chip preset multiple patterns. Particular examples are presented for customized patterns that were encoded into the metasurface with a single-cell meta-atom, working simultaneously at RGB color channels and for several different diffractive distances, with polarization dependence. Holographic images are generated at 18 independent channels with such a single-cell metasurface. The proposed design scheme is easy to implement, and the resulting device is viable for fabrication, promising plenty of applications in nanophotonics.

The evolving landscape of IL-10, IL-22 and IL-26 in pleurisy especially in tuberculous pleurisy.

Pleurisy can be categorized as primary or secondary, arising from immunological, tumorous, or microbial conditions. It often results in lung structure damage and the development of various respiratory issues. Among the different types, tuberculous pleurisy has emerged as a prominent focus for both clinical and scientific investigations. The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy. This review aims to present a detailed overview of the intricate role of IL-10 family members (specifically IL-10, IL-22, and IL-26) in human and animal pleuritic diseases or relevant animal models. These insights could serve as valuable guidance and references for further studies on pleurisy and potential therapeutic strategies.

Multimodal Theranostic Nanoparticles for Necrosis Targeting, Fluorescence/SPECT Imaging, and Radiotherapy of Residual Tumors after Hepatocellular Carcinoma Ablation.

Thermal ablation has been commonly used as an effective treatment for hepatocellular carcinoma; however, peri-necrotic tumor residues after ablation play a significant role in tumor recurrence and poor prognosis. Therefore, developing agents that can effectively target and eliminate residual tumors is critically needed. Necrosis targeting strategies have potential implications for evaluating tumor necrosis areas and treating the surrounding residual tumors. To address this issue, we have developed a biodegradable nanoparticle with necrosis avidity that is compatible with fluorescence imaging, single photon emission computed tomography (SPECT) imaging, and necrosis targeted radiotherapy. The nanoparticles were synthesized using iodine-131-labeled hypericin (131I-Hyp) as the core and amphiphilic copolymer poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as the shell. The developed nanoparticle, PNP@(131I-Hyp), has a uniform spherical morphology with a size of 33.07 ± 3.94 and 45.93 ± 0.58 nm determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light-scattering analysis (polydispersity index = 0.19 ± 0.01), respectively, and having a good stability and blood compatibility in vitro. In mouse subcutaneous ablated-residual tumor models, fluorescence and SPECT imaging demonstrated that PNP@(131I-Hyp) prominently accumulated in the tumor and was retained for as long as 168 h following intravenous injection. Moreover, ex vivo analyses showed that PNP@(131I-Hyp) mainly gathered in the necrotic zones of subcutaneous tumors and inhibited residual tumors by radiotherapy. In addition, histological examination of harvested organs and hematological analysis demonstrated that intravenous injection of 5 mCi/kg nanoparticles caused no gross abnormalities. This multifunctional nanoparticle, therefore, has necrosis imaging and targeted therapeutic effects on residual tumors after thermal ablation of hepatocellular carcinoma, showing potential for clinical application.

Suppression of DNMT1 combined with ATM or ATR inhibitor as a therapeutic combination of acute myeloid leukemia.

The potential treatment option of targeting DNA methyltransferase 1 (DNMT1) has been explored, but further investigation is required to assess the efficacy of combination therapy in acute myeloid leukemia (AML). In this study, bioinformatics and online databases were utilized to select the combined therapeutic targets. The potential kinases associated with DNMT1-related genes in AML were analyzed using the Cancer Genome Atlas (TCGA) database and X2K Appyter (Expression2Kinases) database. In-vitro evaluations were conducted to assess the synergistic effects between DNMT1 and ATR/ATM in five AML cell lines (MOLM-16, NB-4, HEL 92.1.7, HEL, EOL-1). In our study, ATR and ATM are primarily the kinases associated with DNMT1-related genes in AML. We observed a significant upregulation of DNMT1, ATR, and ATM expression in AML tissues and cell lines. The five AML cell lines demonstrated sensitivity to monotherapy with GSK-368, AZD-1390, or AZD-6738 (EC50 value ranges from 5.461 to 7.349 nM, 5.821 to 10.120 nM, and 7.618 to 10.100 nM, respectively). A considerable synergistic effect was observed in AML cell lines when combining GSK-368 and AZD-1390, GSK-368 and AZD-6738, or AZD-1390 and AZD-6738, resulting in induced cell apoptosis and inhibited cell growth. DNMT1, ATM, and ATR possess potential as therapeutic targets for AML. Both individual targeting and combination targeting of these molecules have been confirmed as promising therapeutic approaches for AML.

Highly Enantioselective Ir-Catalyzed Hydrogenation of Pyrazolo[1,5-a]pyrimidine for the Synthesis of Zanubrutinib.

A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.

Cu2O-catalyzed cascade phosphinylation/cyclization of 2'-aminochalcones for the synthesis of hemi-indigo derivatives.

A Cu2O-catalyzed cascade phosphinylation/cyclization reaction of 2'-aminochalcones and diphenylphosphine oxides to produce hemi-indigo derivatives has been developed. This strategy facilitates the sequential formation of a C-P bonds and a C-N bond in a single reaction step. Notably, the approach features one-pot operation, an earth-abundant copper catalyst, readily available starting materials, a broad substrate scope and high compatibility with functional groups, providing 33 compounds in acceptable yields.

Dynamic Behavior and Interaction Mechanism of Soil Organic Matter in Water Systems: A Coarse-Grained Molecular Dynamics Study.

Investigating soil organic matter's (SOM) microscale assembly and functionality is challenging due to its complexity. This study constructs comparatively realistic SOM models, including diverse components such as Leonardite humic acid (LHA), lipids, peptides, carbohydrates, and lignin, to unveil their spontaneous self-assembly behavior at the mesoscopic scale through microsecond coarse-grained molecular dynamics simulations. We discovered an ordered SOM aggregation creating a layered phase from its hydrophobic core to the aqueous phase, resulting in an increasing O/C ratio and declining structural amphiphilicity. Notably, the amphiphilic lipids formed a bilayer membrane, partnering with lignin to constitute SOM's hydrophobic core. LHA, despite forming a layer, was embedded within this structure. The formation of such complex architectures was driven by nonbonded interactions between components. Our analysis revealed component-dependent diffusion effects within the SOM system. Lipids, peptides, and lignin showed inhibitory effects on self-diffusion, while carbohydrates facilitated diffusion. This study offers novel insights into the dynamic behavior and assembly of SOM components, introducing an effective approach for studying dynamic SOM mechanisms in aquatic environments.

New Mechanism for the Apoptosis of Human Neuroblastoma Cells by the Interaction between Fluorene-9-Bisphenol and the G Protein-Coupled Estrogen Receptor 1.

Fluorene-9-bisphenol (BHPF) is an emerging contaminant. Presently, there is no report on its interaction with G protein-coupled estrogen receptor 1 (GPER). By using an integrated toxicity research scenario that combined theoretical study with experimental methods, BHPF was found to inhibit the GPER-mediated effect via direct receptor binding. Molecular dynamics simulations found that Trp2726.48 and Glu2756.51 be the key amino acids of BHPF binding with GPER. Moreover, the calculation indicated that BHPF was a suspected GPER inhibitor, which neither can activate GPER nor is able to form water channels of GPER. The role of two residues was successfully verified by following gene knockout and site-directed mutagenesis assays. Further in vitro assays showed that BHPF could attenuate the increase in intracellular concentration of free Ca2+ induced by G1-activated GPER. Besides, BHPF showed an enhanced cytotoxicity compared with G15, indicating that BHPF might be a more potent GPER inhibitor than G15. In addition, a statistically significant effect on the mRNA level of GPER was observed for BHPF. In brief, the present study proposes that BHPF be a GPER inhibitor, and its GPER molecular recognition mechanism has been revealed, which is of great significance for the health risk and assessment of BHPF.

Precisely Identifying the Sources of Magnetic Particles by Hierarchical Classification-Aided Isotopic Fingerprinting.

Magnetic particles (MPs), with magnetite (Fe3O4) and maghemite (γ-Fe2O3) as the most abundant species, are ubiquitously present in the natural environment. MPs are among the most applied engineered particles and can be produced incidentally by various human activities. Identification of the sources of MPs is crucial for their risk assessment and regulation, which, however, is still an unsolved problem. Here, we report a novel approach, hierarchical classification-aided stable isotopic fingerprinting, to address this problem. We found that naturally occurring, incidental, and engineered MPs have distinct Fe and O isotopic fingerprints due to significant Fe/O isotope fractionation during their generation processes, which enables the establishment of an Fe-O isotopic library covering complex sources. Furthermore, we developed a three-level machine learning model that not only can distinguish the sources of MPs with a high precision (94.3%) but also can identify the multiple species (Fe3O4 or γ-Fe2O3) and synthetic routes of engineered MPs with a precision of 81.6%. This work represents the first reliable strategy for the precise source tracing of particles with multiple species and complex sources.