Development and validation of an automated computational approach to grade immune effector cell-associated hematotoxicity.

Hematologic toxicity frequently complicates chimeric antigen receptor (CAR) T-cell therapy, resulting in significant morbidity and mortality. In an effort to standardize reporting, the European Hematology Association (EHA) and European Society of Blood and Marrow Transplantation (EBMT) devised the immune effector cell-associated hematotoxicity (ICAHT) grading system, distinguishing between early (day 0-30) and late (after day +30) events based on neutropenia depth and duration. However, manual implementation of ICAHT grading criteria is time-consuming and susceptible to subjectivity and error. To address these challenges, we introduce a novel computational approach, utilizing the R programming language, to automate early and late ICAHT grading. Given the complexities of early ICAHT grading, we benchmarked our approach both manually and computationally in two independent cohorts totaling 1251 patients. Our computational approach offers significant implications by streamlining grading processes, reducing manual time and effort, and promoting standardization across varied clinical settings. We provide this tool to the scientific community alongside a comprehensive implementation guide, fostering its widespread adoption and enhancing reporting consistency for ICAHT.

Biobased Inks Based on Cuttlefish Ink and Cellulose Nanofibers for Biodegradable Patterned Soft Actuators.

Soft actuators with stimuli-responsive and reversible deformations have shown great promise in soft robotics. However, some challenges remain in existing actuators, such as the materials involved derived from nonrenewable resources, complex and nonscalable preparation methods, and incapability of complex and programmable deformation. Here, a biobased ink based on cuttlefish ink nanoparticles (CINPs) and cellulose nanofibers (CNFs) was developed, allowing for the preparation of biodegradable patterned actuators by direct ink writing technology. The hybrid CNF/CINP ink displays good rheological properties, allowing it to be accurately printed on a variety of flexible substrates. A bilayer actuator was developed by printing an ink layer on a biodegradable poly(lactic acid) film using extrusion-based 3D printing technology, which exhibits reversible and large bending behavior under the stimuli of humidity and light. Furthermore, programmable and reversible folding and coiling deformations in response to stimuli have been achieved by adjusting the ink patterns. This work offers a fast, scalable, and cost-effective strategy for the development of biodegradable patterned actuators with programmable shape-morphing.

Conventional and novel [18F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma.

Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [18F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

BACKGROUND AND PURPOSE: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease.

Microbial transformation of bile acids affects intestinal immune homoeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. In addition, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.

Ultrasensitive Flexible Temperature Sensors Based on Thermal-Mediated Ions Migration Dynamics in Asymmetrical Polymer Bilayers.

Accurately acquiring crucial data on the ambient surroundings and physiological processes delivered via subtle temperature fluctuation is vital for advancing artificial intelligence and personal healthcare techniques but is still challenging. Here, we introduce an electrically induced cation injection mechanism based on thermal-mediated ion migration dynamics in an asymmetrical polymer bilayer (APB) composed of nonionic polymer and polyelectrolyte layers, enabling the development of ultrasensitive flexible temperature sensors. The resulting optimized sensor achieves ultrahigh sensitivity, with a thermal index surpassing 10,000 K-1, which allows identifying temperature differences as small as 10 mK with a sensitivity that exceeds 1.5 mK. The mechanism also enables APB sensors to possess good insensitivity to various mechanical deformations─features essential for practical applications. As a proof of concept, we demonstrate the potential impact of APB sensors in various conceptual applications, such as mental tension evaluation, biomimetic thermal tactile, and thermal radiation detection.

Efficient Electron Transfer through Interfacial Water Molecules across Two-Dimensional MoO3 for Humidity Sensing.

Resistive humidity sensors are required in flexible and integrated devices. Two-dimensional MoO3 offers a large interface area, enabling the modulation of its electrical properties over a wide range. In this study, 2D MoO3 was synthesized via liquid-phase exfoliation for humidity-sensing tests. In terms of high sensitivity, negligible hysteresis, linearity, and stability, the humidity-sensing performance of MoO3 is superior to those of other materials. The sensitivity reaches 9794 Ω/RH at 25 °C. The sensing mechanism of MoO3 was investigated by using impedance spectra and voltage-current scans under different humidity levels. The results indicate that the resistance change of MoO3 due to humidity originates from the interfacial conductance. Interfacial H2O adsorption induces efficient conducting paths via hydrogen bonding, decreases the potential barrier for electron transfer, and supplies additional electron states to the valence bands. In this study, electronic humidity sensing was investigated in depth, and a new perspective was proposed for electronic humidity sensing.

Mortality risk of people living with HIV under hypothetical intervention scenarios of PM2.5 and HIV severity: a prospective cohort study.

This study estimated and compared mortality risks among people living with HIV (PLWH) under the real-world and hypothetical scenarios of PM2.5 concentrations and HIV severity. An open cohort from all PLWH receiving antiretroviral therapy in Sichuan during 2010-2019 was constructed, resulting in 541,515 person-years. Annual mean concentrations of PM2.5 were estimated and linked to PLWH by their residential address. The parametric g-formula were used to assess 3- and 5-year mortality risks under the real-world and hypothetical scenarios of PM2.5 (10-35, 35-50, 50-75 µg/m3) and CD4 concentrations (0-200, 200-500, 500-800, 800-1100 counts/µl). The estimated 3- and 5-year mortality risks among the PLWH were 14.43 % and 19.38 %, respectively, which would decrease substantially when annual PM2.5 concentration were reduced to between 10 and 35 µg/m3 (risk difference [RD] = -3.23 % and - 4.06 %) and would increase when PM2.5 concentration were elevated to between 50 and 75 µg/m3 (RD = 3.59 % and 5.04 %). The mortality risk would increase when CD4 concentration were reduced to <200 counts/µl (RD = 15.90 % and 20.27 %) and would decrease when CD4 concentration were ≥ 200 counts/µl, especially to between 800 and 1100 counts/µl (RD = -9.01 % and - 11.75 %). The elevated concentration of PM2.5 may disproportionately affect individuals with immune deficiency, especially those with more severity. The findings would serve as justifications for future intervention design and policy making to alleviate air pollution and improve environmental justice and health equity.

Latent Class Proportional Hazards Regression with Heterogeneous Survival Data.

Heterogeneous survival data are commonly present in chronic disease studies. Delineating meaningful disease subtypes directly linked to a survival outcome can generate useful scientific implications. In this work, we develop a latent class proportional hazards (PH) regression framework to address such an interest. We propose mixture proportional hazards modeling, which flexibly accommodates class-specific covariate effects while allowing for the baseline hazard function to vary across latent classes. Adapting the strategy of nonparametric maximum likelihood estimation, we derive an Expectation-Maximization (E-M) algorithm to estimate the proposed model. We establish the theoretical properties of the resulting estimators. Extensive simulation studies are conducted, demonstrating satisfactory finite-sample performance of the proposed method as well as the predictive benefit from accounting for the heterogeneity across latent classes. We further illustrate the practical utility of the proposed method through an application to a mild cognitive impairment (MCI) cohort in the Uniform Data Set.

Design Strategies towards Advanced Hydrogen Evolution Reaction Electrocatalysts at Large Current Densities.

Hydrogen (H2), produced by water electrolysis with the electricity from renewable sources, is an ideal energy carrier for achieving a carbon-neutral and sustainable society. Hydrogen evolution reaction (HER) is the cathodic half-reaction of water electrolysis, which requires active and robust electrocatalysts to reduce the energy consumption for H2 generation. Despite numerous electrocatalysts have been reported by the academia for HER, most of them were only tested under relatively small current densities for a short period, which cannot meet the requirements for industrial water electrolysis. To bridge the gap between academia and industry, it is crucial to develop highly active HER electrocatalysts which can operate at large current densities for a long time. In this review, the mechanisms of HER in acidic and alkaline electrolytes are firstly introduced. Then, design strategies towards high-performance large-current-density HER electrocatalysts from five aspects including number of active sites, intrinsic activity of each site, charge transfer, mass transfer, and stability are discussed via featured examples. Finally, our own insights about the challenges and future opportunities in this emerging field are presented.

Differential oral and gut microbial structure related to systemic metabolism in kidney stone patients.

OBJECTIVES: To investigate the role of the oral and gut microbiome related to systemic metabolism and clinical parameters in various types of kidney stone disease. PATIENTS AND METHODS: We conducted a case-control study by analyzing 16S rRNA and untargeted metabolomics profiling of 76 fecal, 68 saliva, 73 urine, and 43 serum samples from 76 participants aged 18-75 years old. The participants included 15 patients with uric acid stones, 41 patients with calcium oxalate stones, and 20 healthy controls. Correlations among microbiome, metabolism, and clinical parameters were identified through Spearman's correlation analysis. (Clinical trial No. ChiCTR2200055316). RESULTS: Patients with uric acid stones exhibited reduced richness and diversity in their microbiome, as well as altered composition in both oral and gut microbiome. Furthermore, their fecal samples showed lower relative abundances of Bacteroides and Lachnospiraceae, while their saliva samples showed higher relative abundances of Porphyromonas and Neisseria. Predicted KEGG metabolism pathways, including amino acid and fatty acid metabolisms, were significantly altered in subjects with uric acid stones. Oral, gut microbiota, and metabolism were also associated with low water intake and urine pH. The area under the curve (AUC) of the specific microbiota and metabolite prediction models was over 0.85. CONCLUSION: The structure and composition of the oral and gut microbiome in different types of kidney stone disease, the correlations between oral and gut microbiome, and the associations among oral and gut microbiota, systemic metabolism and clinical parameters imply an important role that the oral and gut microbiome may play in kidney stone disease.

Anthracene and tetraphenylsilane based conjugated porous polymer nanoparticles for sensitive detection of nitroaromatics in water.

Conjugated porous polymers (CPPs) are a kind of promising sensing materials for the detection of nitroaromatic compounds, but their sensing applications in aqueous media are limited because of their poor dispersity or solubility in water. In this study, we prepared anthracene and tetraphenylsilane based CPPs named PSiAn by conventional Suzuki coupling and Suzuki-miniemulsion polymerization, respectively. The structure, morphology and porosity of the CPPs were characterized by Fourier Transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), transmission electron microscope (TEM) and N2 sorption isotherm, respectively. Both of the CPPs have porous structure which is beneficial for the adsorption and diffusion of the analytes within them. The particle size of PSiAn nanoparticles prepared by Suzuki-miniemulsion polymerization is 10-40 nm from the TEM image, which facilitates the dispersion in the aqueous phase. Combined with the porosity and nanoparticle morphology, PSiAn nanoparticles realized the efficient photoluminescence (PL) sensing of nitroaromatic explosives in aqueous phase. The limit of detection (LOD) and limit of quantitation (LOQ) of PSiAn nanoparticles for 2,4,6-trinitrophenol (TNP) detection in the pure aqueous phase are 0.33 µM and 1.11 µM, respectively. Meanwhile, the good selectivity and anti-interference in presence of other nitro-compounds were observed. Furthermore, the spike/recovery test for the TNP detection in real water samples by PL sensing based on PSiAn nanoparticles indicates the quantitative recovery of TNP from 100.74 % to 101.00 %. The electrochemical test, ultraviolet-visible absorption spectra, excitation and emission spectra, and time-resolved PL spectra were investigated to explore the PL sensing mechanism. As a result, it is found that the fluorescence inner filter effect might be the predominant quenching mechanism during the detection of nitrophenolic compounds such as TNP and 4-nitrophenol (4-NP).

Intrinsic targeting of host RNA by Cas13 constrains its utility.

Cas13 can be used for the knockdown, editing, imaging or detection of RNA and for RNA-based gene therapy. Here by using RNA immunoprecipitation sequencing, transcriptome profiling, biochemical analysis, high-throughput screening and machine learning, we show that Cas13 can intrinsically target host RNA in mammalian cells through previously unappreciated mechanisms. Different from its known cis/trans RNA-cleavage activity, Cas13 can also cleave host RNA via mechanisms that are transcript-specific, independent of the sequence of CRISPR RNA and dynamically dependent on the conformational state of Cas13, as we show for several Cas13-family effectors encoded in one-vector and two-vector lentiviral systems. Moreover, host genes involved in viral processes and whose transcripts are intrinsically targeted by Cas13 contribute to constraining the lentiviral delivery and expression of Cas13. Our findings offer guidance for the appropriate use of lentiviral Cas13 systems and highlight the need for caution regarding intrinsic RNA targeting in Cas13-based applications.

Research progress in risk factors of post-transplantation diabetes mellitus / 器官移植

Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.

Utilization of diverse oligosaccharides for growth by Bifidobacterium and Lactobacillus species and their in vitro co-cultivation characteristics.

Various approaches have been used to study the relationship between prebiotics and probiotics. The utilization of different carbohydrates by probiotics depends on the biochemical properties of the enzymes and substrates required by the microbial strain. However, few studies have systematically analyzed the ability of probiotics to utilize different prebiotics. Here, we investigated the effects of prebiotics from different manufacturers on the proliferation of 13 strains of the Lactobacillus group and the genus Bifidobacterium co-cultured in vitro. Inulin, fructose-oligosaccharide (FOS), and galactose-oligosaccharide (GOS) had broad growth-promoting effects. FOS significantly promoted the proliferation of B. longum. When strains from Lactobacillus group and Bifidobacterium were co-cultured, FOS caused each strain to proliferate cooperatively. GOS was effectively used by L. rhamnosus and L. reuteri for energy and growth promotion. L. casei and L. paracasei fully metabolized inulin; these strains performed better than other strains from Lactobacillus group and Bifidobacterium. Media containing a mixture of oligosaccharides had stronger effects on the growth of B. animalis subsp. lactis, L. acidophilus, and L. rhamnosus than media containing single oligosaccharides. Thus, different oligosaccharides had different effects on the growth of probiotics, providing a scientific basis for the use of synbiotics in health and related fields.

Research on multi-strategy improved sparrow search optimization algorithm.

To address the issues with inadequate search space, sluggish convergence and easy fall into local optimality during iteration of the sparrow search algorithm (SSA), a multi-strategy improved sparrow search algorithm (ISSA), is developed. First, the population dynamic adjustment strategy is carried out to restrict the amount of sparrow population discoverers and joiners. Second, the update strategy in the mining phase of the honeypot optimization algorithm (HBA) is combined to change the update formula of the joiner's position to enhance the global exploration ability of the algorithm. Finally, the optimal position of population discoverers is perturbed using the perturbation operator and levy flight strategy to improve the ability of the algorithm to jump out of local optimum. The experimental simulations are put up against the basic sparrow search algorithm and the other four swarm intelligence (SI) algorithms in 13 benchmark test functions, and the Wilcoxon rank sum test is used to determine whether the algorithm is significantly different from the other algorithms. The results show that the improved sparrow search algorithm has better convergence and solution accuracy, and the global optimization ability is greatly improved. When the proposed algorithm is used in pilot optimization in channel estimation, the bit error rate is greatly improved, which shows the superiority of the proposed algorithm in engineering application.

Backbone Isomerization to Enhance Thermal Stability and Decrease Mechanical Sensitivities of 10 Nitro-Substituted Bipyrazoles.

The development of novel, environmentally friendly, and high-energy oxidizers remains interesting and challenging for replacing halogen-containing ammonium perchloride (AP). The trinitromethyl moiety is one of the most promising substituents for designing high-energy density oxidizers. In this study, a backbone isomerization strategy was utilized to manipulate the properties of 10 nitro group-substituted bipyrazoles containing the largest number of nitro groups among the bis-azole backbones so far. Another advanced high-energy density oxidizer, 3,3',5,5'-tetranitro-1,1'-bis(trinitromethyl)-1H,1'H-4,4'-bipyrazole (3), was designed and synthesized. Compared to the isomer 4,4',5,5'-tetranitro-2,2'-bis(trinitromethyl)-2H,2'H-3,3'-bipyrazole (4) (Td = 125 °C), 3 possesses better thermostability (Td = 156 °C), which is close to that of ammonium dinitramide (ADN) (Td = 159 °C), and it possesses better mechanical sensitivity (impact sensitivity (IS) = 13 J and friction sensitivity (FS) = 240 N) than that of 4 (IS = 9 J and FS = 215 N), thereby demonstrating a promising perspective for practical applications.

Tetraphenylethene-Based Cross-Linked Conjugated Polymer Nanoparticles for Efficient Detection of 2,4,6-Trinitrophenol in Aqueous Phase.

The cross-linked conjugated polymer poly(tetraphenylethene-co-biphenyl) (PTPEBP) nanoparticles were prepared by Suzuki-miniemulsion polymerization. The structure, morphology, and pore characteristics of PTPEBP nanoparticles were characterized by FTIR, NMR, SEM, and nitrogen adsorption and desorption measurements. PTPEBP presents a spherical nanoparticle morphology with a particle size of 56 nm; the specific surface area is 69.1 m2/g, and the distribution of the pore size is centered at about 2.5 nm. Due to the introduction of the tetraphenylethene unit, the fluorescence quantum yield of the PTPEBP nanoparticles reaches 8.14% in aqueous dispersion. Combining the porosity and nanoparticle morphology, the fluorescence sensing detection toward nitroaromatic explosives in the pure aqueous phase has been realized. The Stern-Volmer quenching constant for 2,4,6-trinitrophenol (TNP) detection is 2.50 × 104 M-1, the limit of detection is 1.07 µM, and the limit of quantification is 3.57 µM. Importantly, the detection effect of PTPEBP nanoparticles toward TNP did not change significantly after adding other nitroaromatic compounds, indicating that the anti-interference and selectivity for TNP detection in aqueous media is remarkable. In addition, the spike recovery test demonstrates the potential of PTPEBP nanoparticles for detecting TNP in natural environmental water samples.

GSH-depleting metal-polyphenol-network nanoparticles with dual enzyme activities induce enhanced ferroptosis.

Ferroptosis is a non-apoptotic form of regulated cell death. The efficiency of ferroptosis is restrained in the tumor microenvironment (TME) by overexpression of glutathione (GSH) and insufficient production of hydrogen peroxide (H2O2). In this work, theranostic nanoparticles Ce-aMOFs@Fe3+-EGCG, termed MEFs, are developed by coating uniform Ce-based amorphous metal-organic frameworks (Ce-aMOFs) with epigallocatechin gallate (EGCG) and Fe3+. Fe3+ is chelated by the adjacent phenol hydroxyl groups in EGCG. In the tumor cell interior, overexpressed GSH and weak acidic medium degrade the coating to release Fe3+ and EGCG accompanied by exposure of Ce-aMOFs. Fe3+ and EGCG consume GSH along with turning Fe3+ into Fe2+. Ce-aMOFs act as a nanozyme possessing dual-enzymatic activities, i.e. superoxide dismutase (SOD)- and phosphatase-like activities. In the TME, Ce-aMOFs catalyze the conversion of endogenous superoxide (O2˙-) into H2O2, and Fe2+ catalyzes H2O2 to generate toxic hydroxyl radicals (˙OH), which may further induce tumor cell death through ferroptosis. In addition, the phosphatase-like activity of Ce-aMOFs may sustainably dephosphorylate NADPH and effectively inhibit intracellular biosynthesis of GSH. Therefore, MEFs ensure down-regulation of intracellular GSH levels and up-regulation of oxidative pressure, which enhance the ferroptosis effect.

Identifying cadmium and lead co-accumulation from living rice blade spectrum.

Neither cadmium (Cd) nor lead (Pb) is necessary for crop growth, but they both can accumulate in soil and crop tissues, resulting in land degradation and crop reduction. Few researchers have explored how to detect Cd-Pb co-accumulation in leaves using proximal sensing techniques, especially by low-cost, easy-to-use leaf clips that capture hyperspectral reflections at suitable foliar positions. In this study, a hyperspectral imager was employed to collect images of the rice canopy from a designed greenhouse experiment that included 16 pretreatments of Cd-Pb co-accumulation, followed by spectral extractions from 3 foliar positions: the blade root, the middle of the leaf, and the leaf apex. A support vector machine with leave-one-out cross-validation was performed to diagnose the contaminative levels based on the feature wavelengths selected by an improved successive projection algorithm. Partial least squares regression was used to predict Cd-Pb concentrations in rice blades. The results indicated that diagnostic accuracies were varied using spectra of different foliar positions. The blade root and leaf apex of rice blades were the optimal foliar position for detecting Cd and Pb contamination, respectively. At the optimal foliar positions, diagnostic accuracies exceeded 0.80 for distinguishing whether the rice is subject to Cd-Pb contamination. The Cd prediction performed 'very good' with a residual prediction deviation (RPD) of 2.21, a R2 of 0.79, and a root mean square error (RMSE)of 6.14, while that of Pb was 1.62, 0.61, and 186.54. Important wavelengths were identified at 659-694 nm and 667-694 nm to detect Cd and Pb contamination. In summary, our results verified the feasibility and clarified the optimal foliar positions of rice blades to detect Cd-Pb contamination. The wavelengths selecting have the great potential in the design of future leaf clips, and the optimal foliar position can provide suggestions to improve diagnostic performances in field applications.