Synthesis and preclinical evaluation of a novel probe [18F]AlF-NOTA-IPB-GPC3P for PET imaging of GPC3 positive tumor.

Glypican-3 (GPC3) is markedly overexpressed in hepatocellular carcinoma (HCC) and not expressed in normal liver tissues. In this study, a novel peptide PET imaging agent ([18F]AlF-NOTA-IPB-GPC3P) was developed to target GPC3 expressed in tumors. The overall radiochemical yield of [18F]AlF-NOTA-IPB-GPC3P was 10-15 %, and its lipophilicity, expressed as the logD value at a pH of 7.4, was -1.18 ± 0.06 (n = 3). Compared to the previously reported tracer [18F]AlF-GP2633, [18F]AlF-NOTA-IPB-GPC3P exhibited higher cellular uptake (15.13 vs 5.96) and internalized rate (80.63 % vs 35.93 %) in Huh7 cells at 120 min. Micro-PET/CT and biodistribution studies further demonstrated that [18F]AlF-NOTA-IPB-GPC3P exhibited significantly increased tumor uptake and prolonged tumor residence in Huh7 tumors compared to [18F]AlF-GP2633 (4.66 ± 0.22 % ID/g vs 0.72 ± 0.09 % ID/g at 60 min, p < 0.001; 5.05 ± 0.23 % ID/g vs 0.35 ± 0.08 % ID/g at 120 min, p < 0.001, respectively). Furthermore, the tumor-to-organ ratios of [18F]AlF-NOTA-IPB-GPC3P surpassed those of [18F]AlF-GP2633. Our results support the utilization of [18F]AlF-NOTA-IPB-GPC3P as a PET imaging agent targeting the GPC3 receptor for tumor detection.

Synthesis and preclinical evaluation of a novel molecular probe [18F]AlF-NOTA-PEG2-Asp2-PDL1P for PET imaging of PD-L1 positive tumor.

Immunotherapy has brought great benefits to cancer patients, but only some patients benefit from it. Noninvasive, real-time and dynamic monitoring of the effectiveness of immunotherapy through PET imaging may provide assistance for the treatment plan of immunotherapy. In this study, we designed and synthesized a new targeted PD-L1 peptide NOTA-PEG2-Asp2-PDL1P, which was labeled with nuclide 18F to obtain a new imaging agent [18F]AlF-NOTA-PEG2-Asp2-PDL1P. The total radiochemical yield of [18F]AlF-NOTA-PEG2-Asp2-PDL1P was 13.7 % (Uncorrected radiochemical yield, n > 5). [18F]AlF-NOTA-PEG2-Asp2-PDL1P achieved high radiochemical purity (>95 %) with a molar activity more than 51.2 GBq/µmol. [18F]AlF-NOTA-PEG2-Asp2-PDL1P exhibited good hydrophilicity and had good stability both in vivo and in vitro, it can specifically targets B16F10 tumor with PD-L1 expression, and had a relatively high retention in tumor, a relatively fast clearance in vivo and a higher tumor-to-non-target ratio, all of which could make [18F]AlF-NOTA-PEG2-Asp2-PDL1P a potential tracer for PD-L1 prediction before clinical immunotherapy.

Hydroalkoxylation of Enamides Catalyzed by N-Heteroarenium Iodides.

A facile and novel N-heteroarenium iodide-catalyzed hydroalkoxylation of enamides has been described. The protocol provides easy access to N,O-acetals, which proved to be a versatile synthetic synthon. The hydrosulfonylation, hydroamination, and hydrophosphorylation products of enamide could be indirectly provided from N,O-acetals. The reaction mechanism was further investigated, which indicated that the hydroalkoxylation of enamides was driven by weak coordination between enamide and the contact ion pair of N-heteroarenium iodide.

Motion-Aware Memory Network for Fast Video Salient Object Detection.

Previous methods based on 3DCNN, convLSTM, or optical flow have achieved great success in video salient object detection (VSOD). However, these methods still suffer from high computational costs or poor quality of the generated saliency maps. To address this, we design a space-time memory (STM)-based network that employs a standard encoder-decoder architecture. During the encoding stage, we extract high-level temporal features from the current frame and its adjacent frames, which is more efficient and practical than methods reliant on optical flow. During the decoding stage, we introduce an effective fusion strategy for both spatial and temporal branches. The semantic information of the high-level features is used to improve the object details in the low-level features. Subsequently, spatiotemporal features are methodically derived step by step to reconstruct the saliency maps. Moreover, inspired by the boundary supervision prevalent in image salient object detection (ISOD), we design a motion-aware loss that predicts object boundary motion, and simultaneously perform multitask learning for VSOD and object motion prediction. This can further enhance the model's capability to accurately extract spatiotemporal features while maintaining object integrity. Extensive experiments on several datasets demonstrate the effectiveness of our method and can achieve state-of-the-art metrics on some datasets. Our proposed model does not require optical flow or additional preprocessing, and can reach an impressive inference speed of nearly 100 FPS.

A bubble-enhanced lanthanide-doped up/down-conversion platform with tumor microenvironment response for dual-modal photoacoustic and near-infrared-II fluorescence imaging.

As an important tumor diagnosis strategy in precision medicine, multimodal imaging has been widely studied. However, the weak imaging signal with low spatial resolution and the constant signal of lack of specific activation severely limit its disease diagnosis. Herein, a bubble-enhanced lanthanide-based up/down-conversion platform with tumor microenvironment response for dual-mode imaging, LDNP@DMSN-Au@CaCO3 nanoparticles (named as LDAC NPs) were successfully developed. Combining the advantages of photoacoustic imaging (PAI) and the second near-infrared window (NIR-II) fluorescence imaging (FI), significantly improved the accuracy of diseases diagnosis. LDAC NPs with flower-like structure were synthesized through the encapsulation of uniform lanthanide-doped nanoparticles (NaYbF4:Ce,Er@NaYF4 named LDNPs) with dendritic mesoporous silica (DMSN). The gold nanoparticles (Au NPs) were then in situ grown on the surface of DMSN and the surface were finally coated with a layer of calcium carbonate (CaCO3). Under the excitation of the 980 nm laser, LDNPs showed strong emission of NIR-II at 1550 nm due to the doping of Ce and Er ions, showcasing excellent spatial resolution and deep tissue penetration characteristics, while the resulting visible light emission (540 nm) enables Au NPs to generate PAI signals with the aid of LDNPs via the fluorescence resonance energy transfer effect. In acidic tumoral environment, CaCO3 layer could produce CO2 microbubbles, and the PAI signals of LDAC NPs could be further enhanced with the generation of CO2 bubbles due to the bubble cavitation effect. Simultaneously, the NIR-II FI of LDAC NPs was self-enhanced with the degradation of the CaCO3. This intelligent nanoparticle with stimulus-activated dual-mode imaging capability holds great promise in future precision diagnostics.

A comparative 18F-FDG and an anti-PD-L1 probe PET/CT imaging of implant-associated Staphylococcus aureus osteomyelitis.

Background: Early and accurate diagnosis of infection-induced osteomyelitis, which often involves increased PD-L1 expression, is crucial for better treatment outcomes. Radiolabeled anti-PD-L1 nuclear imaging allows for sensitive and non-invasive whole-body assessments of PD-L1 expression. This study aimed to compare the efficacy of 18F-FDG and an 18F-labeled PD-L1-binding peptide probe (18F-PD-L1P) in PET imaging of implant-associated Staphylococcus aureus osteomyelitis (IAOM). Methods: In this study, we synthesized an anti-PD-L1 probe and compared its efficacy with 18F-FDG and 18F-PD-L1P in PET imaging of implant-associated Staphylococcus aureus osteomyelitis (IAOM). The %ID/g ratios (i.e., radioactivity ratios between the infected and non-infected sides) of both probes were evaluated for sensitivity and accuracy in post-infected 7-day tibias and post-infected 21 days, and the intensity of 18F-PD-L1P uptake was compared with pathological changes measured by PD-L1 immunohistochemistry (IHC). Results: Compared with 18F-FDG, 18F-PDL1P demonstrated higher %ID/g ratios for both post-infected 7-day tibias (P=0.001) and post-infected 21 days (P=0.028). The intensity of 18F-PD-L1P uptake reflected the pathological changes of osteomyelitic bones. In comparison to 18F-FDG, 18F-PDL1P provides earlier and more sensitive detection of osteomyelitis caused by S. aureus. Conclusion: Our findings suggest that the 18F-PDL1P probe is a promising tool for the early and accurate detection of osteomyelitis caused by S. aureus.

[Systematic evaluation of the incidence of the knee donor area after autobone cartilage mosaic xentoplasty].

OBJECTIVE: To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty. METHODS: A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed. RESULTS: A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7). CONCLUSION: Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.

A diphosphoramidite ligand for hydroformylation of various olefins.

A new rotationally hindered diphosphoramidite ligand has been applied to the Rh-catalyzed hydroformylation of various olefins. Good activity as well as excellent regioselectivity toward the formation of linear aldehydes were achieved. Remarkable performances were also observed in the hydroformylation of functionalized olefins, including methyl acrylate, allyl acetate, crotonaldehyde ethylene acetal and styrene.

Three-dimensional quantitative structural-activity relationship and molecular dynamics study of multivariate substituted 4-oxyquinazoline HDAC6 inhibitors.

3D-QSAR models were established by collecting 46 multivariate-substituted 4-oxyquinazoline HDAC6 inhibitors. The relationship of molecular structure and inhibitory activity was studied by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). The results showed the models established by CoMFA (q2 = 0.590, r2 = 0.965) and CoMSIA (q2 = 0.594, r2 = 0.931) had good prediction ability. At the same time, 3D-QSAR models met the internal verification, external verification and AD test. Ten new compounds were designed based on CoMFA and CoMSIA contour maps and their pharmacokinetic/toxic properties (ADME/T) were evaluated. It was found that most compounds have well safety profile and pharmacokinetic property. Then, we explored the interaction between HDAC6 and compounds by molecular docking. The results showed that the binding mode of the new compounds with HDAC6 was the same as the template compound 46, and the hydrogen bond and hydrophobic bond played a vital role in the binding process. Molecular dynamics simulation results showed that residues Ser531, His574 and Tyr745 played key roles in the binding process. All newly designed compounds had lower energy gap and binding energy than compound 46 according to DFT analysis and free energy analysis. This study provided a theoretical reference for designing compounds of higher activity and a new idea for the development of novel HDAC6 inhibitors.

Advances in hydrophilic metal-organic frameworks for N-linked glycopeptide enrichment.

The comprehensive profiling of glycoproteins is of great significance for the timely clinical diagnosis and therapy. However, inherent obstacles hamper their direct analysis from biological samples, and specific enrichment prior to analysis is indispensable. Among the various approaches for glycopeptide enrichment, hydrophilic interaction liquid chromatography (HILIC) has attracted special focus, especially for the development of novel hydrophilic materials, which is the key of HILIC. Metal-organic frameworks (MOFs) are a type of porous materials constructed from the self-assembly of metal and organic linkers. Advantages such as high surface area, flexible pore size, and easy modification render hydrophilic MOFs as ideal candidates for HILIC, which has inspired many studies over the past years. In this review, advances in hydrophilic MOFs for N-linked glycopeptide enrichment are summarized. According to the synthesis strategies, those materials are categorized into three classes, namely pristine MOFs, MOFs with chemical modifications, and MOFs-derived composite. In each categorization, the preparation and the function of different moieties are covered, as well as the enrichment performances of sensitivity, selectivity, and practical application. Finally, a summary and future perspective on the applications of hydrophilic MOFs for N-linked glycopeptide enrichment are briefly discussed. This review is expected to raise awareness of the properties of hydrophilic MOFs and offer some valuable information to further research in glycoproteomics.

Position Fusing and Refining for Clear Salient Object Detection.

Multilevel feature fusion plays a pivotal role in salient object detection (SOD). High-level features present rich semantic information but lack object position information, whereas low-level features contain object position information but are mixed with noises such as backgrounds. Appropriately addressing the gap between low-and high-level features is important in SOD. We first propose a global position embedding attention (GPEA) module to minimize the discrepancy between multilevel features in this article. We extract the position information by utilizing the semantic information at high-level features to resist noises at low-level features. Object refine attention (ORA) module is introduced to refine features used to predict saliency maps further without any additional supervision and heighten discriminative regions near the salient object, such as boundaries. Moreover, we find that the saliency maps generated by the previous methods contain some blurry regions, and we design a pixel value (PV) loss to help the model generate saliency maps with improved clarity. Experimental results on five commonly used SOD datasets demonstrated that the proposed method is effective and outperforms the state-of-the-art approaches on multiple metrics.

Comparison of femoral mechanics before and after internal fixation removal and the effect of sclerosis on femoral stress: a finite element analysis.

BACKGROUND: Femoral neck fractures are a common traumatic injury. The removal of the internal fixation remains controversial, especially in terms of mechanical stability. Moreover, collapsed necrosis of the femoral head continues to occur after fracture healing. We believe that sclerotic cancellous bone (SCB) formation around the screw is associated with femoral head necrosis. We aimed to compare mechanical features before and after implant removal and determine the effect of SCB formation on stress distribution. METHODS: Cylindrical cancellous bone sections were collected from a relatively normal region and an SCB region of a necrotic femoral head, and their elastic moduli were measured. Four femoral finite element models were developed: a) femoral neck fracture healing with implants, b) fracture healing without implants, c) sclerosis around the screw with implants, and d) sclerosis around the screw without implants. RESULTS: The maximum von Mises peak stresses of models a and b were 66.643 MPa and 63.76 MPa, respectively, and were concentrated in the upper lateral femur. The main stress was scattered at the lowest screw tail, femoral calcar region, and lateral femur shaft. Moreover, coronal plane strain throughout the screw paths near the femoral head in models a and b was mostly in the range of 1000-3000 µÎµ. The maximum stress concentrations in models c and d were located at the lower femoral head and reached 91.199 MPa and 78.019 MPa, respectively. CONCLUSIONS: The stresses in the sclerotic model around the cannulated screws are more concentrated on the femoral head than in the healing model without sclerotic bone. The overall stresses in the healing femoral neck fracture model were essentially unchanged before and after removal of the internal fixation.

Micro-Computed Tomography Analysis of Femoral Head Necrosis After Long-Term Internal Fixation for Femoral Neck Fracture.

OBJECTIVE: To analyze necrotic femoral head after long-term internal fixation for femoral neck fractures using micro-computed tomography (CT) for bone histomorphometry. METHODS: The experimental group included six patients (two men and four women; mean age 62.00 ± 9.36 years) who underwent hip arthroplasty at 47.67 ± 14.22 months after internal fixation. Surgery was performed because of femoral head necrosis after femoral neck fracture between October 2018 and October 2020. The control group included three patients (two men and one woman; mean age 69.33 ± 4.62 years) who underwent hip arthroplasty for femoral neck fracture. In the experimental group, micro-CT quantitative analysis of the whole femur, sclerotic region around screws, screw paths, sclerotic region and screw paths, and relatively normal region was performed. The bone volume fraction (BV/TV), number of bone trabeculae (Tb.N), connection density (Conn.D), thickness of bone trabeculae (Tb.Th), separation of bone trabeculae (Tb.SP), structural model index (SMI), and bone mineral density (BMD) of each part were quantitatively analyzed. RESULTS: The BV/TV (0.3180 ± 0.0617), Conn.D (6.9261 ± 2.4715/mm3 ), Tb.Th (0.3262 ± 0.0136 µm), and BMD (298.9241 ± 54.2029 g/cm3 ) of the sclerotic region around the screws were significantly higher in the experimental group than the BV/TV (0.1248 ± 0.0390), Conn.D (2.5708 ± 0.5187/mm3 ), Tb.Th (0.1713 ± 0.0333 µm), and BMD (66.5181 ± 43.0380 g/cm3 ) in the control group (P < 0.05). The BV/TV (0.2222 ± 0.0684), Tb.Th (0.2775 ± 0.0326 µm), and BMD (195.0153 ± 71.8509 g/cm3 ) in the collapsed region were significantly higher in the experimental group than in the control group (P < 0.05). In the experimental group, the volume ratio of the sclerotic region around screws and screw paths to the entire femoral head was 0.4964 ± 0.0950. CONCLUSION: After internal fixation for femoral neck fracture, a large number of sclerotic plate-like trabeculae were observed around the long-term retained implant. The screw paths and surrounding sclerotic comprise approximately 50% of the femoral head volume.

[Clinical effects of arthroscopy-assisted anterior cruciate ligament tibial eminence avulsion fracture compared with traditional open surgery:a Meta-analysis].

OBJECTIVE: To systematically evaluate the clinical efficacy of arthroscopy and traditional incision in the treatment of tibial avulsion fracture of anterior cruciate ligament (ACL). METHODS: From July 2010 to July 2020, clinical comparative trial about arthroscopy and traditional incision in the treatment of ACL tibial avulsion fracture was conducted by using computer-based databases, including Embase, Pubmed, Central, Cinahl, PQDT, CNKI, Weipu, Wanfang, Cochrane Library, CBM. Literature screening and data extraction were carried out according to the inclusion and exclusion criteria, and the quality of the included literature was evaluated by improved Jadad score and Ottawa Newcastle scale (NOS). The operation time, hospital stay, fracture healing time, knee range of motion, postoperative excellent and good rate, complication rate, Lysholm score, International Knee Documentation Committee (IKDC) score and Tegner score were statistically analyzed by Review Manager 5.3 software. RESULTS: Finally, 16 literatures were included, including 1 randomized controlled trial and 15 non randomized controlled trials, with a total of 822 patients (405 in arthroscopy group and 417 in traditional incision group). Meta analysis showed that the operation time [MD=-9.03, 95% CI(-14.36, -3.70), P<0.001], hospital stay [MD=-5.81, 95%CI(-9.32, -2.31), P=0.001] and fracture healing time [MD=-14.61, 95% CI(-17.93, -11.28), P<0.001] in the arthroscopy group were better than those in the traditional incision group. The incidence of complications in arthroscopy group was lower than that in traditional incision group[OR=0.15, 95%CI(0.07, 0.33), P<0.001]. The postoperative excellent and good rate[OR=4.39, 95%CI (1.96, 9.82), P<0.001], knee mobility[MD=6.78, 95%CI(2.79, 10.77), P<0.001], Lysholm score[MD=11.63, 95%CI(4.91, 18.36), P<0.001], IKDC score[MD=7.83, 95%CI(6.09, 9.57), P<0.001] and Tegner score[MD=0.60, 95%CI(0.31, 0.89), P<0.001] in the arthroscopic group were higher than those in the traditional incision group. CONCLUSION: Compared with the traditional open reduction and internal fixation, arthroscopic surgery in patients with ACL tibial avulsion fracture can shorten the operation time, hospital stay and fracture healing time, reduce the incidence of postoperative complications, and obtain good postoperative knee function. It can be recommended as one of the first choice for patients with ACL tibial avulsion fracture.

Stabilization of Chemical-Vapor-Deposition-Grown WS2 Monolayers at Elevated Temperature with Hexagonal Boron Nitride Encapsulation.

Chemical vapor deposition (CVD)-grown flakes of high-quality monolayers of WS2 can be stabilized at elevated temperatures by encapsulation with several layer hexagonal boron nitride (h-BN), but to different degrees in the presence of ambient air, flowing N2, and flowing forming gas (95% N2, 5% H2). The best passivation of WS2 at elevated temperature occurs for h-BN-covered samples with flowing N2 (after heating to 873 K), as judged by optical microscopy and photoluminescence (PL) intensity after a heating/cooling cycle. Stability is worse for uncovered samples, but best with flowing forming gas. PL from trions, in addition to that from excitons, is seen for covered WS2 only for forming gas, during cooling below ∼323 K; the trion has an estimated binding energy of ∼28 meV. It might occur because of doping level changes caused by charge defect generation by H2 molecules diffusing between the h-BN and the SiO2/Si substrate. The decomposition of uncovered WS2 flakes in air suggests a dissociation and chemisorption energy barrier of O2 on the WS2 surface of ∼1.6 eV. Fitting the high-temperature PL intensities in air gives a binding energy of a free exciton of ∼229 meV.

Novel insights into overcoming nitrite oxidation bacteria acclimatization problem in treatment of high-ammonia wastewater through partial nitrification.

A partial nitrification sequencing batch reactor was operated to reveal mechanisms behind nitrite oxidation bacteria (NOB) acclimatization in high-ammonia wastewater treatment. The influent NH4+-N increased stepwise from 499.7 ± 4.2 mg/L to 6994.5 ± 7.5 mg/L with initial free ammonia (FA) concentration rising from 37.9 ± 3.2 mg NH3-N/L to 715.3 ± 47.3 mg NH3-N/L, respectively. NOB acclimatized this FA range with NO3--N production increasing from 29.2 ± 2.6 mg/L to 144.1 ± 31.0 mg/L in a cycle, which was caused by the shift of dominant NOB genus from Nitrospira to Nitrolencea. Nitrosomonas as ammonia oxidation bacteria, could sustain its activity of 62.1 ± 0.1 mg NH4+-N/(gVSS∙L∙h) under the same condition. Hydroxylamine addition could be implemented as an emergency measure to alleviate NOB acclimatization in short-term operation. The findings expanded knowledge about NOB acclimatization types and provided novel insights for addressing this problem in a targeted way.

Efficient and advanced nitrogen removal from mature landfill leachate via combining nitritation and denitritation with Anammox in a single sequencing batch biofilm reactor.

A novel combined partial nitrification-Anammox and partial denitrification-Anammox (PnA/PdA) single sequencing batch biofilm reactor (SBBR) was established to realize efficient and advanced nitrogen removal from mature landfill leachate with low biodegradability. Nitrogen removal rate and nitrogen removal efficiency were increased to 2.83 ± 0.06 kgN/(m3∙d) and 98.6 ± 0.2% by stepwise increase of dissolved oxygen (DO, from 0.5 to 3.5 mg/L) and continuous carbon source feeding. Comparable activities of ammonia oxidation bacteria and Anammox bacteria were realized during aerobic period. More organic carbon was redirected from complete denitrification to partial denitrification during anoxic period. The main pathway PnA jointly synergized with PdA, which contributed to 76.04% and 19.44% nitrogen removal, respectively. Nitrosomonas, Thauera, and Kuenenia dominated in floc sludge (0.78%, 5.38%, and 1.14%, respectively) and biofilm (0.34%, 5.18%, and 0.98%, respectively). Overall, this study provides new insight into the high-efficiency treatment of landfill leachate at full-scale landfill sites.

Palladium-Catalyzed Domino Reaction for Stereoselective Synthesis of Multisubstituted Olefins: Construction of Blue Luminogens.

The first Pd-catalyzed multicomponent reaction of aryl iodides, alkenyl bromides, and strained alkenes has been developed, which allowed us to synthesize a variety of multisubsituted olefins in yields of 45-96% with excellent stereoselectivity. The configuration of the product was controlled by the configuration of the alkenyl bromides. Moreover, this practical methodology employing readily available substrates was found to be tolerant to a wide range of functional groups. Fifty six examples of highly stereoselective tri- or tetrasubstituted olefins have been successfully synthesized via this methodology. Most of the synthesized tetrasubstituted olefins are good aggregation-induced emission (AIE) luminogens.

Core/Shell Microstructure Induced Synergistic Effect for Efficient Water-Droplet Formation and Cloud-Seeding Application.

Cloud-seeding materials as a promising water-augmentation technology have drawn more attention recently. We designed and synthesized a type of core/shell NaCl/TiO2 (CSNT) particle with controlled particle size, which successfully adsorbed more water vapor (∼295 times at low relative humidity, 20% RH) than that of pure NaCl, deliquesced at a lower environmental RH of 62-66% than the hygroscopic point (hg.p., 75% RH) of NaCl, and formed larger water droplets ∼6-10 times its original measured size area, whereas the pure NaCl still remained as a crystal at the same conditions. The enhanced performance was attributed to the synergistic effect of the hydrophilic TiO2 shell and hygroscopic NaCl core microstructure, which attracted a large amount of water vapor and turned it into a liquid faster. Moreover, the critical particle size of the CSNT particles (0.4-10 µm) as cloud-seeding materials was predicted via the classical Kelvin equation based on their surface hydrophilicity. Finally, the benefits of CSNT particles for cloud-seeding applications were determined visually through in situ observation under an environmental scanning electron microscope on the microscale and cloud chamber experiments on the macroscale, respectively. These excellent and consistent performances positively confirmed that CSNT particles could be promising cloud-seeding materials.