Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

Raman encoding for security labels: a review.

Owing to its excellent multiplexing ability, high stability, and molecular fingerprint characteristics, Raman encoding has been widely used in security labels for medical safety, jewelry identification and food supervision. Various growing demands have promoted the anti-counterfeiting mode of security labels based on Raman encoding from the classic one that relies on specific patterns to the more secure one that depends on random patterns. As impressive progress has been made in Raman encoding for security labels in recent years, this review attempts to comprehensively cover security labels based on Raman encoding, from label preparation to image verification. For the labels with different anti-counterfeiting modes, the different basic elements they need are summarized, and the role of Raman encoding in different modes is introduced. In addition, security labels based on Raman encoding still have some drawbacks. Therefore, suggestions on how to improve its anti-counterfeiting performance are also discussed, as well as future challenges and prospects.

"Dramatic Growth" of Microbial Aerosols for Visualization and Accurate Counting of Bioaerosols.

While the global COVID-19 pandemic has subsided, microbial aerosol detection has become of high concern. Timely, accurate, and highly sensitive monitoring of microbial aerosols in indoor air is the basis for effective prevention and control of infectious diseases. At present, no commercial equipment or reliable technology can simultaneously control the detection time and limit at 6 h and 102 CFU/mL, respectively. Based on the "safety size range" of particulate matter in the air, we propose a new method of microbial dilation detection, which enables the pathogen to grow rapidly and dramatically into a polymeric microsphere, larger in size than the coexisting aerosol particles. "Like a crane standing among chickens", the microorganism can be easily visualized and counted. Different from routine chemical and biological sensing technologies, this method can achieve absolute counting of microbial particles, and the simple principles can be developed into devices for different life scenarios.

A cooling-driven self-adaptive and removable hydrogel coupled with combined chemo-photothermal sterilization for promoting infected wound healing.

Hydrogel dressings that can fit irregular wounds, promote wound healing, and detach from wounds without damage represent the development trend of modern medical dressings. Herein, a novel composite hydrogel with excellent wound shape matching and painless removability via a gel-sol phase transition is constructed through dynamic borate ester bonds between phenylboronic acid-grafted F127 (PF127) and polydopamine-coated reduced graphene oxide/silver nanoparticles (rGO@PDA/Ag NPs). After contact with the skin tissues, the administered liquid-like sols gradually transform into solid-like gels, robustly adhering to the wound. The hydrogel dressings containing near-infrared (NIR)-responsive rGO@PDA and in situ formed Ag NPs can generate localized heat and gradually release Ag+ to realize safe, effective, and durable photothermal-chemical combined sterilization. In addition, catechol-rich PDA endows the hydrogel dressings with good antioxidant activity and adhesiveness. In vivo study results indicate that the hydrogel dressings can significantly accelerate full-thickness skin infected wound healing by eliminating bacteria, promoting collagen deposition and angiogenesis, as well as reducing inflammation. Collectively, the thermoreversible rGO@PDA/Ag-PF127 hydrogel dressings with an improved self-adapting ability, superior antimicrobial activity, and tunable adhesion appear to be a promising candidate for the treatment of infected wounds.

Cancer survival: left truncation and comparison of results from hospital-based cancer registry and population-based cancer registry.

Background: Cancer survival is an important indicator for evaluating cancer prognosis and cancer care outcomes. The incidence dates used in calculating survival differ between population-based registries and hospital-based registries. Studies examining the effects of the left truncation of incidence dates and delayed reporting on survival estimates are scarce in real-world applications. Methods: Cancer cases hospitalized at Nantong Tumor Hospital during the years 2002-2017 were traced with their records registered in the Qidong Cancer Registry. Survival was calculated using the life table method for cancer patients with the first visit dates recorded in the hospital-based cancer registry (HBR) as the diagnosis date (OSH), those with the registered dates of population-based cancer (PBR) registered as the incidence date (OSP), and those with corrected dates when the delayed report dates were calibrated (OSC). Results: Among 2,636 cases, 1,307 had incidence dates registered in PBR prior to the diagnosis dates of the first hospitalization registered in HBR, while 667 cases with incidence dates registered in PBR were later than the diagnosis dates registered in HBR. The 5-year OSH, OSP, and OSC were 36.1%, 37.4%, and 39.0%, respectively. The "lost" proportion of 5-year survival due to the left truncation for HBR data was estimated to be between 3.5% and 7.4%, and the "delayed-report" proportion of 5-year survival for PBR data was found to be 4.1%. Conclusion: Left truncation of survival in HBR cases was demonstrated. The pseudo-left truncation in PBR should be reduced by controlling delayed reporting and maximizing completeness. Our study provides practical references and suggestions for evaluating the survival of cancer patients with HBR and PBR.

Blood-Glucose-Depleting Hydrogel Dressing as an Activatable Photothermal/Chemodynamic Antibacterial Agent for Healing Diabetic Wounds.

Poorly healing and nonhealing diabetic wounds are challenging to treat as the rapid growth of bacteria due to the high local glucose content can lead to persistent inflammation and poor angiogenesis. Herein, a smart hydrogel dressing composed of 3,3',5,5'-tetramethylbenzidine/ferrous ion/Pluronic F-127/glucose oxidase (TMB/Fe2+/PF127/GOx) is designed and demonstrated to consume blood glucose while accelerating wound healing by generating antibacterial agents in situ. The loaded GOx degrades blood glucose to provide hydrogen peroxide (H2O2) and gluconic acid to support the Fe2+-based Fenton reaction, and the generated hydroxyl radical (·OH) facilitates the oxidation of TMB. The color change from colorless to green caused by the oxidation of TMB in the blood glucose range between 1 and 10 mM can be monitored visually. Simultaneously, this process induced chemodynamic therapy (CDT) by the specific generation of hydroxyl radical (·OH) for killing bacteria. Moreover, the oxidized TMB shows strong absorption in the near infrared (NIR) region so that NIR light can be converted into heat efficiently for photothermal therapy (PTT). As a result, nearly 100% of Staphylococcus aureus and Escherichia coli are killed by synergistic PTT/CDT, and the infected skin wounds undergo complete repair along with downregulation of interleukin-6 (IL-6) and upregulation of the vascular endothelial growth factor (VEGF) and matrix metallopeptidase-2 (MMP-2). Different from traditional wound dressings that can give rise to secondary injury, the excellent thermosensitive properties arising from the sol/gel phase transition render the hydrogel dressing materials injectable, self-reparable, and removable on demand. The multifunctional hydrogel with hypoglycemic, chemodynamic, photothermal, antibacterial, and on-demand thermosensitive properties has immense potential in the treatment of diabetic wounds.

Engineering a SERS Sensing Nanoplatform with Self-Sterilization for Undifferentiated and Rapid Detection of Bacteria.

The development of a convenient, sensitive, rapid and self-sterilizing biosensor for microbial detection is important for the prevention and control of foodborne diseases. Herein, we designed a surface-enhanced Raman scattering (SERS) sensing nanoplatform based on a capture-enrichment-enhancement strategy to detect bacteria. The gold-Azo@silver-cetyltrimethylammonium bromide (Au-Azo@Ag-CTAB) SERS nanotags were obtained by optimizing the synthesis process conditions. The results showed that the modification of CTAB enabled the nanotags to bind to different bacteria electrostatically. This SERS sensing nanoplatform was demonstrated to be fast (15 min), accurate and sensitive (limit of detection (LOD): 300 and 400 CFU/mL for E. coli and S. aureus, respectively). Of note, the excellent endogenous antibacterial activity of CTAB allowed the complete inactivation of bacteria after the assay process, thus effectively avoiding secondary contamination.

Silent Raman imaging of highly effective anti-bacterial activity synchronous with biofilm breakage using poly(4-cyanostyrene)@silver@polylysine nanocomposites.

Biofilms are known to be a great challenge for their anti-bacterial activity as they obstruct drug action for deeper and more thorough bacteria-killing effects. Therefore, developing highly effective antibacterial agents to destroy biofilms and eradicate bacteria is of great significance. Herein, a new type of nanocomposites (denoted as poly(4-cyanostyrene)@silver@polylysine) is proposed, in which polylysine (PLL) could rapidly capture the biofilms and exhibit excellent antibacterial efficacy together with decorated silver (Ag) nanoparticles (NPs) through the charge effect and Ag+ release. Notably, nearly 100% antibacterial rates against Gram-positive bacterium (Staphylococcus aureus, S. aureus) and Gram-negative bacterium (Escherichia coli, E. coli) were achieved. More importantly, poly(4-cyanostyrene) with biological silent Raman imaging capacity is able to illustrate the relationship between antibacterial efficiency and biofilm breakage. In short, such novel nanocomposites can improve the bioavailability of each component and display tremendous potential in antibacterial applications.

Raman inks based on triple-bond-containing polymeric nanoparticles for security.

Developing security inks with spectral outputs/multiple colors, which have unique identification characteristics, is of great importance in enhancing the anti-counterfeiting strength of ink anti-counterfeiting technology. Herein, a print-driven triple-bond coding mode is proposed for the first time. Two kinds of triple-bond-containing polymeric nanoparticles (NPs) with Raman shifts at 2227 and 2241 cm-1 have been designed into printable ink, and the decimal coding output can be easily obtained by reasonably adjusting the proportions of the two polymeric NPs. Single Raman scattering inks can be used as invisible inks to print monochromatic patterns and words that the decoder can read out. According to the two-dimensional pixels of the graphics decoder, invisible colorful graphics can be printed with mixed inks under different polymer proportions. More interestingly, three-dimensional invisible patterns with stronger anti-counterfeiting strength can also be obtained in the double-layer anti-counterfeiting patterns with different proportions of ink by the spatial complementary coding mode. It is predicted that more security inks associated with triple-bond Raman signals will spur the application of the anti-counterfeiting field.

Photoreduced Ag+ surrounding single poly(4-cyanostyrene) nanoparticles for undifferentiated SERS sensing and killing of bacteria.

Developing a rapid, low cost and sensitive sensing strategy for undifferentiated detection and fast killing of bacterial pathogens are critical to alleviating bacteria infections. Here, we propose a direct photoreduction method to synthesize the SERS tag by integrating poly(4-cyanostyrene) nanoparticles (NPs) and silver ions, which are applied as bio-sensing system for bacteria sensing and fast killing. Under a focused laser spot, silver ions on the surface of the poly(4-cyanostyrene) NPs could be photoreduced into Ag NPs, thereby causing the Raman signal amplification of poly(4-cyanostyrene) NPs up to 40 times, and there is a good linear correlation between the Raman intensity of poly(4-cyanostyrene) NPs and different concentrations of Ag+. Moreover, 4-mercaptophenylboronic acid, performing the same recognition function for both the Gram-positive and Gram-negative bacteria, is used as bridge between the bacteria and Ag+ by the inherent chemical bonding. Based on further constructed bio-sensing system, we achieved the quick count and killing of both Gram-positive bacteria, e.g., Staphylococcus aureus (S. aureus), and Gram-negative bacteria, e.g., Escherichia coli (E. coli). Notably, the sensing strategy can detect at least ∼100 cells of E. coli, ∼10 cells of S. aureus and ∼10 cells of their mixture in less than 40 min. The detection accuracy for actual samples can also reach over 80% and the bacteria were entirely killed by Ag+ after the detection, avoiding bacterial contamination in the environment. This novel method is anticipated to perform as a simple yet effective tool for fast and sensitive bacteria counting and killing.

Rational synthesis of Three-Layered plasmonic nanocomposites of copper Sulfide/Gold/Zinc-Doped Prussian blue analogues for improved photothermal disinfection and wound healing.

Bacteria-infected wounds have imposed serious challenges in human health whereas the abuse of antibiotics makes bacteria drug-resistant and becoming more and more difficult to deal with. Herein, we developed a drug-free three-layered photothermal bactericide from inside to outside consisting of copper sulfide (CuS), gold (Au) and zinc-doped Prussian blue analogues (ZnPBA) (named as CuS@Au@ZnPBA). The CuS@Au@ZnPBA was demonstrated to possess remarkably-improved photothermal property and excellent biosafety. Local heat generated by CuS@Au@ZnPBA under the irradiation of 808 nm laser enables efficient bacteria ablation in vitro and in a mouse model of cutaneous wound infection. Meanwhile, the released zinc ions (Zn2+) could upregulate the genes involved in collagen deposition to accelerate wound healing. Overall, the finely-designed nanocomposites can serve as a promising kind of antibacterial alternative to current antibiotic therapies against bacterial wound infections.

Liver Cancer Survival: A Real World Observation of 45 Years with 32,556 Cases.

BACKGROUND AND AIMS: To explore the long-term trend of liver cancer survival, based on the real-world data (RWD) in the past 45 years from a population-based cancer registry, in Qidong, China. METHODS: A number of 32,556 patients with liver cancer were registered during the period of 1972 to 2016. Mixed methods by active and passive follow-up were performed. Life table method was employed for survival analysis by SPSS22 software. Wilcoxon (Gehan) statistics was considered as a significant test. Relative survival was calculated by using SURV software, and its annual percent change (APC) was estimated by the Joinpoint Regression Program. RESULTS: The overall observed survival (OS) rates of 1-, 5-, 10-, and 20-year rates from the data series were 18.51%, 6.28%, 4.03%, and 2.84%, and their relative survival (RS) rates were 18.88%, 6.95%, 4.96%, and 4.49%, respectively. For 24,338 male cases, the 5-year OS and RS rates were 5.93% and 6.54%, and for 8218 female cases, 7.34% and 8.15%, respectively, with P values less than 0.01. Survival rates of liver cancer from three 15-year periods of 1972-1986, 1987-2001, and 2002-2016 have increased significantly, with 5-year OS rates of 2.02%, 4.40%, and 10.76%, 5-year RS rates of 2.18%, 4.83%, and 12.18%; 10-year OS and RS rates of 0.95%, 3.00%, and 7.02%, vs 1.13%, 3.65%, and 8.96%, respectively, showing a very significant upward trend (P<0.01). There are significant differences among age groups (P<0.01): those aged 55-64 demonstrated the best OS and RS rates of 5-year, being 8.44% and 9.09%, respectively. CONCLUSION: There are significant gender and age differences in the survival rate of liver cancer in Qidong. RWD indicates the relative lower survival rate of liver cancer in this area, but great improvement has been achieved over the past decades.

Precise Encoding of Triple-Bond Raman Scattering of Single Polymer Nanoparticles for Multiplexed Imaging Application.

Stimulated Raman scattering (SRS) microscopy in combination with innovative tagging strategies offers great potential as a universal high-throughput biomedical imaging tool. Here, we report rationally tailored small molecular monomers containing triple-bond units with large Raman scattering cross-sections, which can be polymerized at the nanoscale for enhancement of SRS contrast with smaller but brighter optical nanotags with artificial fingerprint output. From this, a class of triple-bond rich polymer nanoparticles (NPs) was engineered by regulating the relative dosages of three chemically different triple-bond monomers in co-polymerization. The bonding strategy allowed for 15 spectrally distinguishable triple-bond combinations. These accurately structured nano molecular aggregates, rather than long-chain macromolecules, could establish a universal method for generating small-sized biological SRS imaging tags with high sensitivity for high-throughput multi-color biomedical imaging.

Promoted "Click" SERS Detection for Precise Intracellular Imaging of Caspase-3.

Although homogeneous detection of some biomolecules has been of great significance in clinical assay, it faces great challenges in achieving precise in situ imaging of biomolecules. In addition, nonspecific adsorption between probes and biomolecules and low sensitivity are still unfathomed problems. Herein, we developed a promoted "Click" surface enhanced Raman scattering (SERS) strategy for realizing highly selective homogeneous detection of biomolecules by simultaneous dual enhanced SERS emissions, obtaining mutually confirmed logical judgment. Taking caspase-3 as one of the biotargets, we have realized highly selective homogeneous detection of caspase-3 using this strategy, and precise intracellular imaging of caspase-3 can be in situ monitored in living cells or during cell apoptosis. In detail, polyA-DNA and the Asp-Glu-Val-Asp (DEVD)-containing peptide sequence were modified into alkyne and nitrile-coded Au nanoparticles (NPs). During the cell apoptosis process, the generated caspase-3 would lead to the cleavage of the tetra-peptide sequence DEVD, thereby removing the negative protection part from the peptide on Au NPs. Interestingly, two different triple bond-labeled Au NPs can be connected together through DNA hybridization to form SERS "hotspot", resulting in simultaneously enlarged triple bond Raman signals. Moreover, we found that the SERS intensity was positively related with caspase-3 concentration, which has a wide linear range (0.1 ng/mL to 10 µg/mL) and low detection limit (7.18 × 10-2 ng/mL). Remarkably, these simultaneously enlarged signals by "Click" SERS could be used for more precise imaging of caspase-3, providing mutually confirmed logical judgment based on two spliced SERS emissions, especially for their relative intensity.

On-site and quantitative SERS detection of trace 1, 2, 3-benzotriazole in transformer oil with colloidal lignin particles-based green pretreatment reagents.

Since 1, 2, 3-Benzotriazole (BTA) is one of the most commonly used metal passivators in transformer oil, on-site and quantitative detection of BTA plays a significant role in fast evaluation of the performance of the insulating oil. Herein, we proposed a cycle-growth synthetic protocol for yielding two-dimensional (2D) plane-based surface-enhanced Raman scattering (SERS) substrates with tunable optical property and controllable interparticle distance, and an extraction material, so called colloidal lignin particles (CLPs), for the fast separation of BTA from oil matrix. After BTA from transformer oil were adsorbed by hydrophilic CLPs, highly reproducible SERS signal of BTA can be obtained by dropping on the substrate. The characteristic Raman shift at 1386 cm-1 of BTA has been selected to establish a good linearity between its relative intensity and concentration in the range of 1-300 mg/L, and the detection limit for BTA was down to 0.12 mg/L. Moreover, the time consumption for the whole detection process of real sample including sample pretreatment and SERS measurements was less than 30 min. It is highly expected that the combination of CLPs with SERS can accomplish the on-site detection of trace BTA in transformer oil.

The small silver nanoparticle-assisted homogeneous sensing of thiocyanate ions with an ultra-wide window based on surface-enhanced Raman-extinction spectroscopy.

For the first time, we present an original sensing strategy with an ultra-wide detection window from 17 nM to 20 mM to detect SCN- ions. Initially, we investigated the clustering and optical properties of noble metal sol nanoparticles (NPs) due to the competitive interaction of thiocyanate ions (SCN-) and cetyltrimethylammonium bromide (CTAB) under weak acidic conditions, and found that different dimensions and scales of nanoclusters containing the alkyne-embedded Au@Ag NPs and relatively small Ag NPs could be achieved by the mediation of CTAB through electrostatic forces and hydrophobic interaction, in which SCN- could be covalently bonded with the silver surface of NPs to form a compact molecular layer (-Ag-S-C[triple bond, length as m-dash]N), and CTAB could only occupy remaining sites. In this process, we found that SCN- always runs counter to CTAB and tends to dissolve nanoclusters, so that they occupy the exposed surface of NPs in nanoclusters rather than the binding sites of one another. Remarkably, when the concentration of SCN- initially increased, two highly recognizable SERS emissions, which were assigned to alkyne reporter molecules (2208 cm-1) and C[triple bond, length as m-dash]N of SCN- (2110 cm-1), respectively, were rapidly detected, and their ratios (I2110/I2208) increased linearly proportional to the concentration of SCN- over a range of 17 nM to 172 µM, with a limit of detection (LOD) of 10 nM. With the further increase of SCN-, small Ag NPs started to desorb from the surface of individual Au@Ag NPs and dissociated in the solution but did not contribute to SERS signals. Instead, the surface plasmon resonance (SPR) peak of pure silver NPs at 385 nm increased gradually in the range from 0.5 to 20 mM with an LOD of 0.2 mM. Of particular significance, this simple sensor in conjunction with surface-enhanced Raman-extinction spectroscopy can be used for the rapid detection of extensive samples with an ultra-wide detection window, such as body fluids (saliva, urine, and serum) and food (milk powder and brassica vegetables), which is far superior to that of ion chromatography (IC).

Liver cancer mortality over six decades in an epidemic area: what we have learned.

BACKGROUND AND AIMS: Liver cancer is one of the most dominant malignant tumors in the world. The trends of liver cancer mortality over the past six decades have been tracked in the epidemic region of Qidong, China. Using epidemiological tools, we explore the dynamic changes in age-standardized rates to characterize important aspects of liver cancer etiology and prevention. METHODS: Mortality data of liver cancer in Qidong from 1958 to 1971 (death retrospective survey) and from 1972 to 2017 (cancer registration) were tabulated for the crude rate (CR), and age-standardized rate and age-birth cohorts. The average annual percentage change was calculated by the Joinpoint Regression Program. RESULTS: The natural death rate during 1958-2017 decreased from 9‰ to 5.4‰ and then increased to 8‰ as the population aged; cancer mortality rates rose continuously from 57/105 to 240/105. Liver cancer mortality increased from 20/105 to 80/105, and then dropped to less than 52/105 in 2017. Liver cancer deaths in 1972-2017 accounted for 30.53% of all cancers, with a CR of 60.48/105, age-standardized rate China (ASRC) of 34.78/105, and ASRW (world) of 45.71/105. Other key features were the CR for males and females of 91.86/105 and 29.92/105, respectively, with a sex ratio of 3.07:1. Period analysis showed that the ASRs for mortality of the age groups under 54 years old had a significant decreasing trend. Importantly, birth cohort analysis showed that the mortality rate of liver cancer in 40-44, 35-39, 30-34, 25-29, 20-24, 15-19 years cohort decreased considerably, but the rates in 70-74, and 75+ increased. CONCLUSIONS: The crude mortality rate of liver cancer in Qidong has experienced trends from lower to higher levels, and from continued increase at a high plateau to most recently a gradual decline, and a change greatest in younger people. Many years of comprehensive prevention and intervention measures have influenced the decline of the liver cancer epidemic in this area. The reduction of intake levels of aflatoxin might be one of the most significant factors as evidenced by the dramatic decline of exposure biomarkers in this population during the past three decades.

Fine synthesis of Prussian-blue analogue coated gold nanoparticles (Au@PBA NPs) for sorting specific cancer cell subtypes.

Multiplex surface-enhanced Raman scattering (SERS) detection of markers without background in tumor biosystems has its superiority over other optical methods. Herein, we reported a strategy of quantitative discrimination of two breast cancer cell subtypes. Based on our previous studies, two kinds of Prussian blue analogue coated gold nanoparticles (Au@PBA NPs) were designed and synthesized by the replacement of Fe2+ with Pb2+ or Cu2+. Therefore, two distinct SERS emissions of C≡N bonds at 2122 cm-1 and 2176 cm-1 have been acquired. When modified with aptamers of epithelial cell adhesion molecule (EpCAM) and epidermal growth factor receptor (EGFR), which are both expressed in MCF-7 and MDA-MB-231 cell lines but in different levels, the SERS nanoprobes simultaneously identified the relative expression of these biomarkers on the cell surface, providing a good example for ratiometric detection in biosystems without any interference. Each surface marker of tumor cells corresponds to a single SERS emission. Thus, each subtype could be described in a molecular profiling way through duplex C≡N bonds-based SERS emission, which is more advanced than traditional flow cytometry method.

Recent advances in plasmonic Prussian blue-based SERS nanotags for biological application.

The reliability and reproducibility of surface-enhanced Raman scattering (SERS) technology is still a great challenge in bio-related analysis. Prussian blue (PB)-based SERS tags have attracted increasing interest for improving these deficiencies due to its unique Raman band (near 2156 cm-1) in the Raman-silent region, providing zero-background bio-Raman labels without interference from endogenous biomolecules. Moreover, the stable PB shell consisting of multiple layers of CN- reporters ensure a stable and strong Raman signal output, avoiding the desorption of the Raman reporter from the plasmonic region by the competitive adsorption of the analyte. More importantly, they possess outstanding multiplexing potential in biological analysis owing to the adjustable Raman shift with unique narrow spectral widths. Despite more attention having been attracted to the structure and preparation of PB-based SERS tags for their better biological applications over the past five years, there is still a great challenge for SERS suitable for applications in the actual environment. The biological applications of PB-based SERS tags are comprehensively recounted in this minireview, mainly focusing on quantification analysis, multiple-spectral analysis and cell-imaging joint phototherapy. The prospects of PB-based SERS tags in clinical diagnosis and treatment are also discussed. This review aims to draw attention to the importance of SERS tags and provide a reference for the design and application of PB-based SERS tags in future bio-applications.

Nucleic Acid Hybridization-Based Noise Suppression for Ultraselective Multiplexed Amplification of Mutant Variants.

The analysis of mutant nucleic acid (NA) variants can provide crucial clinical and biological insights for many diseases. Yet, existing analysis techniques are generally constrained by nonspecific "noise" signals from excessive wildtype background sequences, especially under rapid isothermal multiplexed target amplification conditions. Herein, the molecular hybridization chemistry between NA bases is manipulated to suppress noise signals and achieve ultraselective multiplexed detection of cancer gene fusion NA variants. Firstly, modified locked NA (LNA) bases are rationally introduced into oligonucleotide sequences as designed "locker probes" for high affinity hybridization to wildtype sequences, leading to enrichment of mutant variants for multiplexed isothermal amplification. Secondly, locker probes are coupled with a customized "proximity-programmed" (SERS) readout which allows precise control of hybridization-based plasmonic signaling to specifically detect multiple target amplicons within a single reaction. Moreover, the use of triple bond Raman reporters endows NA noise signal-free quantification in the Raman silent region (≈1800-2600 cm-1 ). With this dual molecular hybridization-based strategy, ultraselective multiplexed detection of gene fusion NA variants in cancer cellular models is actualized with successful noise suppression of native wildtype sequences. The distinct benefits of isothermal NA amplification and SERS multiplexing ability are simultaneously harnessed.