Feasibility and safety study of ultrasound-guided percutaneous microwave ablation for Sub-cardiac liver cancers without artificial ascites assistance.

OBJECTIVES: To investigate the efficacy and safety of ultrasound(US)-guided microwave ablation (MWA) without artificial ascites (AA) inpatients with sub-cardiac liver cancers. MATERIALS AND METHODS: This retrospective study included patients with the left lobe and caudate lobe of the liver cancer who underwent US-guided MWA in our institute from January 2020 to December 2022. According to whether the target lesion was located ≤ 5 mm from the pericardium, patients were divided into the sub-cardiac (SC) group and the non-sub-cardiac (NSC) group. In the SC group, AA was not employed during the ablation procedure. The results of technical success, technical efficiency, local tumor progression (LTP), and major complications were recorded. RESULTS: A total of 79 patients with 87 lesions were enrolled. There were 38 patients with 38 lesions in the SC group and 41 patients with 49 lesions in the NSC group. The median follow-up of all patients was 15 (range, 3-44) months. There was no significant difference in technical success rates (100% versus 100%), technique efficiency rates (100% versus 95.7%), LTP rates (2.63% versus 0%,), and major complication rates (2.63% versus 7.32%) between the SC group and the NSC group (p > 0.05). No cardiac-related complications occurred. CONCLUSIONS: US-guided MWA without AA for sub-cardiac liver cancers was safe and effective. ADVANCES IN KNOWLEDGE: The clinical prognosis of thermal ablation without artificial ascites in the treatment of sub-cardiac liver cancers is still unclear. The finding of this study provided evidence supporting the efficacy and safety of ultrasound-guided microwave ablation without artificial ascites for treating this tricky location.

Research on the Mechanism and Propagation Characteristics of Combustion and Explosion of Natural Gas/Ammonia/Hydrogen Mixed Gas Fuel.

The addition of ammonia and hydrogen into natural gas fuel is an effective method to reduce carbon emissions. This study aims to investigate the effect of adding ammonia and hydrogen on the mechanism of natural gas combustion and emission characteristics. Based on a self-developed mixed gas deflagrate experimental platform, the deflagrate characteristics, emission characteristics, and chemical reaction kinetics mechanism of mixed gas fuels under different composition ratios (natural gas 0-100%, hydrogen 10-85%, and ammonia 0-100%) were studied. The results indicate that the propagation of the deflagration shock wave can be categorized into an initial stage (L < 3 m) and a development stage (L > 3 m) based on the observed trend of shock wave intensity variation with distance. The intensity of the deflagration shock wave for the mixed gases increases monotonically as the hydrogen content ratio rises. In contrast, the impact of the ammonia content ratio on the shock wave intensity exhibits a distinct pattern that varies with changes in the equivalence ratio and hydrogen content ratio. In terms of carbon emissions per unit of heat value produced by the fuel, adding hydrogen to natural gas proves to be more effective at reducing carbon emissions than adding ammonia. When the ammonia content ratio is 50% and the hydrogen content ratio is 40%, the combustion performance of the mixed gas fuel is similar to that of natural gas, but its carbon emissions are lower than 30% of natural gas, making it a new type of mixed fuel with potential application value; the interaction between reflected pressure waves and flames is the main reason for the fluctuation of deflagrate shock wave pressure; ammonia lowers the temperature of the reaction system by reducing the concentration of OH radicals.

Proteome Fishing for CRISPR/Cas12a-Based Orthogonal Multiplex Aptamer Sensing.

Detection of serum protein biomarkers is extremely challenging owing to the superior complexity of serum. Here, we report a method of proteome fishing from the serum. It uses a magnetic nanoparticle-protein corona and a multiplexed aptamer panel, which we incubated with the nanoparticle-protein corona for biomarker recognition. To transfer protein biomarker detection to aptamer detection, we established a CRISPR/Cas12a-based orthogonal multiplex aptamer sensing (COMPASS) platform by profiling the aptamers of protein corona with clinical nonsmall cell lung cancer (NSCLC) serum samples. Furthermore, we determined the four out of nine (FOON) panel (including HE4, NSE, AFP, and VEGF165) to be the most cost-effective and accurate panel for COMPASS in NSCLC diagnosis. The diagnostic accuracy of NSCLC by the FOON panel with internal and external cohorts was 95.56% (ROC-AUC = 99.40%) and 89.58% (ROC-AUC = 95.41%), respectively. Our developed COMPASS technology circumvents the otherwise challenging multiplexed serum protein amplification problem and avoids aptamer degradation in serum. Therefore, this novel COMPASS could lead to the development of a facile, cost-effective, intelligent, and high-throughput diagnostic platform for large-cohort cancer screening.

Accuracy evaluation of a universal dental implant guide for simulating implantation in posterior area on dental molds.

OBJECTIVES: This study aims to compare the accuracy of self-developed universal implant guide (SDG), 3D printed digital guide (DG), and free hand (FH) simulated implantation in the posterior tooth area of dental models. METHODS: Ten junior dentists were selected to place three implants in the 35, 37, and 46 tooth sites of the mandibular models (35, 36, 37, and 46 missing teeth) by using SDG, DG, and FH, and the process was repeated again to take the average value. Cone beam computed tomography (CBCT) was used to evaluate the global coronal deviation, global apical deviation, depth deviation, and angular deviation between the actual position and preoperative planned position. RESULTS: The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly different from those in the two other groups (P>0.05). The depth deviation and angular deviation in the SDG group were smaller than those in the DG group (P<0.05) and FH group (P<0.05), respectively. All deviations at site 37 in the SDG group were not different from those at site 35 (P>0.05), while the depth and angular deviation at site 37 in the DG group were higher than those at site 35 (P<0.05). CONCLUSIONS: The precision of the self-developed universal dental implant guide can meet the requirements of clinical posterior implantation.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

BACKGROUND: To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. AIM: To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. METHODS: A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. RESULTS: Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. CONCLUSION: TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Correlation analysis of interstitial maturity and prognosis of colorectal cancer: Meta-analysis.

BACKGROUND: To investigate the relationship between interstitial maturity and prognosis of colorectal cancer. AIM: To examine the correlation between interstitial maturity and the prognosis of colorectal cancer. METHODS: The paper database PubMed, EMBASE, Cochranelibrary, Springerlink, CNKI, and Wanfang database were searched until December 2023. "tumor stroma maturity" "desmoplastic stroma reaction" "desmoplastic reaction" "stroma reaction" "degree of stroma reaction "" stroma classification" "stroma density" "colorectal cancer" "colon cancer" "rectal cancer" "prognosis" were searched for the search terms. Two system assessors independently screened the literature quality according to the inclusion exclusion criteria, Quality evaluation and data extraction were performed for the included literatures, and meta-analysis was performed for randomized control trials included at using Review Manager 5.2 software. RESULTS: Finally, data of 9849 patients with colorectal cancer from 19 cosets in 15 literatures were included, including 4339 patients with mature type (control group), 3048 patients with intermediate type (intermediate group) and 2456 patients with immature type (immature group). The results of meta-analysis showed: Relapse-free survival [hazard ratio (HR) = 2.66, 95% confidence interval (CI): 2.30-3.08; P < 0.00001], disease-free survival (HR = 3.68, 95%CI: 2.33-5.81; P < 0.00001) and overall survival (HR = 1.70, 95%CI: 1.53-1.87; P < 0.00001) were significantly lower than those in mature group (control group); relapse-free survival (HR = 1.36, 95%CI: 1.17-1.59; P < 0.0001) and disease-free survival rate (HR = 1.85, 95%CI: 1.53-2.24; P < 0.0001) was significantly lower than the mature group (control group). CONCLUSION: There is the correlation between tumor interstitial maturity and survival prognosis of colorectal cancer, and different degrees of tumor interstitial maturity have a certain impact on the quality of life of colorectal cancer patients.

SH-Alb inhibits phenotype remodeling of pro-fibrotic macrophage to attenuate liver fibrosis through SIRT3-SOD2 axis.

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment.

Data-Driven Design of Triple-Targeted Protein Nanoprobes for Multiplexed Imaging of Cancer Lymphatic Metastasis.

Targeted imaging of cancer lymphatic metastasis remains challenging due to its highly heterogeneous molecular and phenotypic diversity. Herein, triple-targeted protein nanoprobes capable of specifically binding to three targets for imaging cancer lymphatic metastasis, through a data-driven design approach combined with a synthetic biology-based assembly strategy, are introduced. Specifically, to address the diversity of metastatic lymph nodes (LNs), a combination of three targets, including C-X-C motif chemokine receptor 4 (CXCR4), transferrin receptor protein 1 (TfR1), and vascular endothelial growth factor receptor 3 (VEGFR3) is identified, leveraging machine leaning-based bioinformatics analysis and examination of LN tissues from patients with gastric cancer. Using this identified target combination, ferritin nanocage-based nanoprobes capable of specifically binding to all three targets are designed through the self-assembly of genetically engineered ferritin subunits using a synthetic biology approach. Using these nanoprobes, multiplexed imaging of heterogeneous metastatic LNs is successfully achieved in a polyclonal lymphatic metastasis animal model. In 19 freshly resected human gastric specimens, the signal from the triple-targeted nanoprobes significantly differentiates metastatic LNs from benign LNs. This study not only provides an effective nanoprobe for imaging highly heterogeneous lymphatic metastasis but also proposes a potential strategy for guiding the design of targeted nanomedicines for cancer lymphatic metastasis.

Effects of Hydrogen Blending Ratio and Equivalence Ratio on the Dynamic Characteristics of Deflagration Shock Waves of CH4/H2 Mixtures.

To evaluate the explosion hazard of CH4/H2 mixtures, experiments were conducted in a long and closed pipeline with a length-to-diameter ratio of 51 and built-in obstacles, and the characteristic parameters of deflagration shock waves were analyzed under different hydrogen blending ratios (0 ≤ λ ≤ 100%) and equivalence ratios (0.5 ≤ Φ ≤ 3). The results indicate that within the range of Φ = 0.8-1.2, the explosion overpressure (P P) exhibits a "two-zone" structure distribution. When 0 ≤ λ ≤ 80%, P P shows an initial increase and then a decrease in both regions, while deflagration to detonation transition (DDT) occurs in the second evolution region when λ = 100%, which is caused by the different strengths of the positive feedback mechanism coupled with flames and shock waves. The P max, (dP/dt)max, and V a show a trend of first increasing and then decreasing and monotonically increasing with the increase of the equivalence ratio and hydrogen blending ratio, respectively, and reach their maximum values at Φ = 1.0 and λ = 100%. For CH4/H2 mixtures with low hydrogen blending ratios (λ = 0 and 20%), the P max and (dP/dt)max in the fuel-lean conditions (Φ = 0.9 and 0.8) are higher than those in the fuel-rich conditions (Φ = 1.1 and 1.2), while the CH4/H2 mixtures under high hydrogen blending ratios (λ = 80 and 100%) are the opposite. Overall, the increase in H2 at a high hydrogen blending ratio and the increase in the equivalence ratio at a fuel-lean condition significantly enhance the average V a. In addition, chemical kinetics analysis found that R38 and R52 elementary reactions are the dominant elementary reactions that promote and inhibit temperature increase, respectively. Their temperature sensitivity coefficients are negatively correlated with the hydrogen blending ratio and positively correlated with the equivalence ratio. The research results provide vital information for evaluating the explosion hazards of CH4/H2 mixtures and developing safety protection measures.

Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial.

The vascular endothelial growth factor pathway plays a key role in the pathogenesis of gastric cancer. In the multicenter, double-blind phase 3 FRUTIGA trial, 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma who progressed on fluorouracil- and platinum-containing chemotherapy were randomized (1:1) to receive fruquintinib (an inhibitor of vascular endothelial growth factor receptor-1/2/3; 4 mg orally, once daily) or placebo for 3 weeks, followed by 1 week off, plus paclitaxel (80 mg/m2 intravenously on days 1/8/15 per cycle). The study results were positive as one of the dual primary endpoints, progression-free survival (PFS), was met (median PFS, 5.6 months in the fruquintinib arm versus 2.7 months in the placebo arm; hazard ratio 0.57; 95% confidence interval 0.48-0.68; P < 0.0001). The other dual primary endpoint, overall survival (OS), was not met (median OS, 9.6 months versus 8.4 months; hazard ratio 0.96, 95% confidence interval 0.81-1.13; P = 0.6064). The most common grade ≥3 adverse events were neutropenia, leukopenia and anemia. Fruquintinib plus paclitaxel as a second-line treatment significantly improved PFS, but not OS, in Chinese patients with advanced gastric or gastroesophageal junction adenocarcinoma and could potentially be another treatment option for these patients. ClinicalTrials.gov registration: NCT03223376 .

Ultra-Large Two-Dimensional Metal Nanowire Networks by Microfluidic Laminar Flow Synthesis for Formic Acid Electrooxidation.

Despite the great research interest in two-dimensional metal nanowire networks (2D MNWNs) due to their large specific surface area and abundance of unsaturated coordination atoms, their controllable synthesis still remains a significant challenge. Herein, a microfluidics laminar flow-based approach is developed, enabling the facile preparation of large-scale 2D structures with diverse alloy compositions, such as PtBi, AuBi, PdBi, PtPdBi, and PtAuCu alloys. Remarkably, these 2D MNWNs can reach sizes up to submillimeter scale (~220 µm), which is significantly larger than the evolution from the 1D or 3D counterparts that typically measure only tens of nanometers. The PdBi 2D MNWNs affords the highest specific activity for formic acid (2669.1 mA mg-1) among current unsupported catalysts, which is 103.5 times higher than Pt-black, respectively. Furthermore, in situ Fourier transform infrared (FTIR) experiments provide comprehensive evidence that PdBi 2D MNWNs catalysts can effectively prevent CO* poisoning, resulting in exceptional activity and stability for the oxidation of formic acid.

Behavioral responses to predator and heterospecific alarm calls are habitat-specific in Eurasian tree sparrows.

Acoustic communication plays a vital role in predator-prey interactions. Although habitat structure has been shown to affect anti-predator tactics, little is known about how animals vary their behaviors in response to predator calls or heterospecific alarm calls in different environments. Here we used sound playbacks to test the responses of Eurasian tree sparrows (Passer montanus) foraging in harvested/unharvested rice paddy and open residential area. In the first experiment, we tested their behavioral responses to dove calls, male common cuckoo (Cuculus canorus) calls, hawk-like calls mimicked by female common cuckoo, sparrowhawk (Accipiter nisus) calls, and human yell calls produced to scare birds (predator signal playbacks). In the second experiment, we tested their behavioral responses to the Japanese tit's (Parus minor) territorial songs and alarm calls (heterospecific alarm signal playbacks). Results showed that the tree sparrows had less fleeing in unharvested ripe rice paddy than in harvested rice paddy and open residential area. In predator signal playbacks, call type affected the escape behavior of sparrows in unharvested rice paddy and open residential area but not harvested rice paddy. In alarm signal playbacks, tit alarm calls evoked more fleeing than territorial songs in harvested rice paddy and open residential area but not unharvested rice paddy. These results suggest that anthropogenic habitat changes may influence avian anti-predator tactics.

Exploring the performance of protected areas in alleviating future human pressure.

Protected areas (PAs) are effective in mitigating human pressures, yet their future pressure alleviating effects remain unclear. In this study, we employed the ConvLSTM model to forecast the future human footprint and analyzed human pressure trends using Theil-Sen median and Mann-Kendall tests. We further evaluated the mitigating effects of PAs within their buffer zones (1-10 km) and the contributions of different IUCN categories of PAs to mitigating human pressure using linear regression models. The results indicate that by 2035, the average human pressure value is expected to increase by 11%, with trends exhibiting a polarized pattern. Furthermore, PAs also effectively mitigate human pressure within their 1 km buffer zones. Different categories of PAs vary in their effectiveness in mitigating human pressure, and stricter conservation areas are not always the most effective. This study can offer insights for evaluating the effectiveness of PAs in reducing human pressure and advocate for their targeted management in urban areas.

NEPE Propellant Mesoscopic Modeling and Damage Mechanism Study Based on Inversion Algorithm.

To accurately characterize the mesoscopic properties of NEPE (Nitrate Ester Plasticized Polyether) propellant, the mechanical contraction method was used to construct a representative volume element (RVE) model. Based on this model, the macroscopic mechanical response of NEPE propellant at a strain rate of 0.0047575 s-1 was simulated and calculated, and the parameters of the cohesive zone model (CZM) were inversely optimized using the Hooke-Jeeves algorithm by comparing the simulation results with the results of the uniaxial tensile test of NEPE propellants. Additionally, the macroscopic mechanical behavior of NEPE composite solid propellants at strain rates of 0.00023776 s-1 and 0.023776 s-1 was also predicted. The mesoscopic damage evolution process of NEPE propellants was investigated by the established model. The study results indicate that the predicted curves are relatively consistent with the basic features and change trends of the test curves. Therefore, the established model can effectively simulate the mesoscopic damage process of NEPE composite solid propellants and their macroscopic mechanical properties.

Genetic identification of human remains from the Korean War.

The genetic identification of skeletal remains from Chinese People's Volunteers (CPVs) of the Korean War has been challenging because of the degraded DNA samples and the lack of living close relatives. This study established a workflow for identifying CPVs by combining Y-chromosome short tandem repeats (Y-STRs), mitochondrial DNA (mtDNA) hypervariable regions I and II, autosomal STRs (aSTRs), and identity-informative SNPs (iiSNPs). A total of 20 skeletal remains of CPVs and 46 samples from their alleged relatives were collected. The success rate of DNA extraction from human remains was 100%. Based on Y-STRs, six remains shared the same male lineages with their alleged relatives. Meanwhile, mtDNA genotyping supports two remains sharing the same maternal lineages with their alleged relatives. Likelihood ratios (LRs) were further obtained from 27 aSTRs and 94 iiSNPs or 1936 iiSNPs to confirm their relationship. All joint pedigree LRs were >100. Finally, six remains were successfully identified. This pilot study for the systematic genetic identification of CPVs from the Korean War can be applied for the large-scale identification of CPVs in the future.

Correction: Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice.

Correction for 'Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice' by Jiayuan Cao et al., Food Funct., 2023, 14, 3259-3268, https://doi.org/10.1039/D2FO03701G.

Self-Assembly of Heterogeneous Ferritin Nanocages for Tumor Uptake and Penetration.

Well-defined nanostructures are crucial for precisely understanding nano-bio interactions. However, nanoparticles (NPs) fabricated through conventional synthesis approaches often lack poor controllability and reproducibility. Herein, a synthetic biology-based strategy is introduced to fabricate uniformly reproducible protein-based NPs, achieving precise control over heterogeneous components of the NPs. Specifically, a ferritin assembly toolbox system is developed that enables intracellular assembly of ferritin subunits/variants in Escherichia coli. Using this strategy, a proof-of-concept study is provided to explore the interplay between ligand density of NPs and their tumor targets/penetration. Various ferritin hybrid nanocages (FHn) containing human ferritin heavy chains (FH) and light chains are accurately assembled, leveraging their intrinsic binding with tumor cells and prolonged circulation time in blood, respectively. Further studies reveal that tumor cell uptake is FH density-dependent through active binding with transferrin receptor 1, whereas in vivo tumor accumulation and tissue penetration are found to be correlated to heterogeneous assembly of FHn and vascular permeability of tumors. Densities of 3.7 FH/100 nm2 on the nanoparticle surface exhibit the highest degree of tumor accumulation and penetration, particularly in tumors with high permeability compared to those with low permeability. This study underscores the significance of nanoparticle heterogeneity in determining particle fate in biological systems.

Oral Milk-Derived Extracellular Vesicles Inhibit Osteoclastogenesis and Ameliorate Bone Loss in Ovariectomized Mice by Improving Gut Microbiota.

Milk-derived extracellular vesicles can improve intestinal health and have antiosteoporosis potential. In this paper, we explored the effects of bovine raw milk-derived extracellular vesicles (mEVs) on ovariectomized (OVX) osteoporotic mice from the perspective of the gut-bone axis. mEVs could inhibit osteoclast differentiation and improve microarchitecture. The level of osteoporotic biomarkers in OVX mice was restored after the mEVs intervened. Compared with OVX mice, mEVs could enhance intestinal permeability, reduce endotoxin levels, and improve the expression of TNF-α, IL-17, and IL-10. 16S rDNA sequencing indicated that mEVs altered the composition of gut microbiota, specifically for Bacteroides associated with short-chain fatty acids (SCFAs). In-depth analysis of SCFAs demonstrated that mEVs could restore acetic acid, propionic acid, valeric acid, and isovaleric acid levels in OVX mice. Correlation analysis revealed that changed gut microbiota and SCFAs were significantly associated with gut inflammation and osteoporotic biomarkers. This study demonstrated that mEVs could inhibit osteoclast differentiation and improve osteoporosis by reshaping the gut microbiota, increasing SCFAs, and decreasing the level of pro-inflammatory cytokines and osteoclast differentiation-related factors in OVX mice. These findings provide evidence for the use of mEVs as a food supplement for osteoporosis.

Serum Protein Fishing for Machine Learning-Boosted Diagnostic Classification of Small Nodules of Lung.

Diagnosis of benign and malignant small nodules of the lung remains an unmet clinical problem which is leading to serious false positive diagnosis and overtreatment. Here, we developed a serum protein fishing-based spectral library (ProteoFish) for data independent acquisition analysis and a machine learning-boosted protein panel for diagnosis of early Non-Small Cell Lung Cancer (NSCLC) and classification of benign and malignant small nodules. We established an extensive NSCLC protein bank consisting of 297 clinical subjects. After testing 5 feature extraction algorithms and six machine learning models, the Lasso algorithm for a 15-key protein panel selection and Random Forest was chosen for diagnostic classification. Our random forest classifier achieved 91.38% accuracy in benign and malignant small nodule diagnosis, which is superior to the existing clinical assays. By integrating with machine learning, the 15-key protein panel may provide insights to multiplexed protein biomarker fishing from serum for facile cancer screening and tackling the current clinical challenge in prospective diagnostic classification of small nodules of the lung.

A nanogap-enhanced SERS nanotag-based lateral flow assay for ultrasensitive and simultaneous monitoring of SARS-CoV-2 S and NP antigens.

A lateral flow assay (LFA) strip based on dual 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB)-encoded satellite Fe3O4@Au (Mag@Au) SERS tags with nanogap is reported for  ultrasensitive and simultaneous diagnosis of two SARS-CoV-2 functional proteins. Composed of Fe3O4 core, satellite gold shell with nanogaps, and double-layer DTNB, the Mag@Au nanoparticles with an average size of 238 nm were designed as multifunctional tags to efficiently enrich the target SARS-CoV-2 protein from complex samples, significantly enhancing the SERS signal of the LFA strip and provide quantitative SERS detection of analyte on test lines. The developed dual DTNB-encoded satellite Mag@Au-based LFA allowed simultaneous quantification of spike (S) protein and nucleocapsid (NP) protein with detection limits of 23 pg mL-1 and 2 pg mL-1, respectively, lower than commercial ELISA kits and reported SERS-LFA detection system-based Au NPs and Fe3O4@3 nm Au MNPs. This magnetic SERS-LFA also showed high performance of multi-variant strain detection and further distinguished clinical samples of Omicron variant infection, demonstrating the potential of in situ detection of respiratory virus diseases.