Background: Targeted next-generation sequencing (tNGS) has emerged as a rapid diagnostic technology for identifying a wide spectrum of pathogens responsible for pulmonary infections.Methods: Sputum samples were collected from patients unable or unwilling to undergo bronchoalveolar lavage. These samples underwent tNGS analysis to diagnose pulmonary infections. Retrospective analysis was performed on clinical data, and the clinical efficacy of tNGS was compared to conventional microbiological tests (CMTs).Results: This study included 209 pediatric and adult patients with confirmed pulmonary infections. tNGS detected 45 potential pathogens, whereas CMTs identified 23 pathogens. The overall microbial detection rate significantly differed between tNGS and CMTs (96.7% vs. 36.8%, p < 0.001). Among the 76 patients with concordant positive results from tNGS and CMTs, 86.8% (66/76) exhibited full or partial agreement. For highly pathogenic and rare/noncolonized microorganisms, tNGS, combined with comprehensive clinical review, directly guided pathogenic diagnosis and antibiotic treatment in 21 patients. This included infections caused by Mycobacterium tuberculosis complex, certain atypical pathogens, Aspergillus, and nontuberculous Mycobacteria. Among the enrolled population, 38.8% (81/209) of patients adjusted their treatment based on tNGS results. Furthermore, tNGS findings unveiled age-specific heterogeneity in pathogen distribution between children and adults.Conclusion: CMTs often fall short in meeting the diagnostic needs of pulmonary infections. This study highlights how tNGS of sputum samples from patients who cannot or will not undergo bronchoalveolar lavage yield valuable insights into potential pathogens, thereby enhancing the diagnosis of pulmonary infections in specific cases.

A novel strategy for screening early hepatocellular carcinoma (HCC) using a terahertz (THz) metamaterials (MMs) biosensor modified with the antibody against Alpha-Fetoprotein (AFP) is proposed. The designed biosensor consists of split-resonant-rings (SRRs) with double resonant frequencies that are optimized using the finite integration time domain (FITD) method and manufactured by a surface micromachining process. The experimental results indicate that the HCC biomarker AFP could be accurately distinguished with a concentration as low as 0.1 ng/ml via analyzing the shifts of double resonant frequencies. Meanwhile, specific detection of AFP-antigen in solution and HCC serum has been achieved through the antigen-antibody specific binding. These results demonstrate the sensitivity and specificity of THz MMs biosensor for molecular detection of trace cancer biomarkers in biochemical sensing. Furthermore, the sensitivity of specific cancer biomarkers can be further improved by optimizing the metamaterial structure and applying the double resonant frequencies. Therefore, this approach may own great potential for special identification of early cancer molecules.

Background: Pulmonary cryptococcosis (PC) and mixed pulmonary infection are difficult to be diagnosed due to the non-specificity and their overlapping clinical manifestations. In terms of the clinical diagnosis of PC and mixed pulmonary infection, conventional tests have limitations such as a long detection period, a limited range of pathogens, and low sensitivity. Metagenomics next-generation sequencing (mNGS) is a nascent and powerful method that can detect pathogens without culture, to diagnose known and unexplained infections in reduced time. Case presentation: A 43-year-old female was admitted to the hospital after suffering from a cough for one month. At the time of admission, a contrast-enhanced chest CT revealed multiple nodules and plaques in her right lung, as well as the formation of cavities. The blood routine assays showed evidently increased white blood cell count (mainly neutrophils), CRP, and ESR, which suggested she was in the infection phase. The serum CrAg-LFA test showed a positive result. Initially, she was diagnosed with an unexplained pulmonary infection. Bronchoalveolar lavage fluid (BALF) samples were collected for microbial culture, immunological tests and the mNGS. Microbial culture and immunological tests were all negative, while mNGS detected Corynebacterium striatum, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Cryptococcus neoformans. The diagnosis was revised to PC and bacterial pneumonia. Lung infection lesions were healed after she received targeted anti-infection therapy with mezlocillin and fluconazole. In a follow-up after 2 months, the patient’s symptoms vanished. Conclusions: Here, we demonstrated that mNGS was capable of accurately distinguishing Cryptococcus from M. tuberculosis in pulmonary infection, and notably mNGS was capable of swiftly and precisely detecting pathogens in mixed bacterial and fungal pulmonary infection. Furthermore, the results of mNGS also have the potential to adjust anti-infective therapies.

We propose a method for diagnosis of cirrhosis and hepatocellular carcinoma (HCC) by using a terahertz (THz) metamaterial (MM) biosensor. The biosensor has a resonance frequency at about 0.801 THz and can measure the concentration of alpha-fetoprotein (AFP) in serum. The sensitivity of the sensor is 124 GHz/refractive index unit (RIU), and the quality-factor (Q) is 6.913, respectively. When the surface of the biosensor is covered with healthy serum ( A F P ≤ 7 n g / m L ), the maximum resonance frequency shift is 50 GHz. However, when it is covered with serum from patients with cirrhosis and early HCC ( A F P > 7 n g / m L ), the resonance frequency shift is more than 59 GHz. Positive correlation exists between the frequency shift of the biosensor and serum levels of the AFP in the HCC patients. This study provides a method for quick diagnosis and prediction of cirrhosis and HCC.

Alpha-fetoprotein (AFP) is closely associated with the occurrence and development of hepatocellular carcinoma (HCC). However, for many HCC patients at early-stage, the AFP concentration is very low and difficult to test. Herein, a terahertz (THz) metamaterials (MMs) biosensor modified with AFP antibody (ATB-AFP) and aptamer (APT-AFP) polymer probe was proposed to detect trace AFP. The biosensor has a theoretical sensitivity of 124 GHz/RIU (Refractive Index Unit), and its experimental limit-of-detection (LOD) is 0.1 ng/mL. When it is modified with AuPEG ₂₀₀₀ -ATB-AFP and AuPEG ₂₀₀₀ -APT-AFP, it sensitivity for AFP antigen in HCC serum is 17.74 GHz/lg(ng/mL) and 15.89 GHz/lg(ng/mL), respectively. The proposed biosensor could detect trace biomarkers at the molecular level, which is significant for diagnosis of the HCC and many other cancers at early stage.