Effectiveness of sarcopenia screening markers in predicting out-of-hospital death in the oldest (≥80 years) older.

OBJECTIVE: The goal of this investigation was to elucidate the correlation between sarcopenia screening indicators (aspartate transaminase/alanine transaminase (AST/ALT) and creatinine/cystatin C*100 (Cr/CysC*100)) and the risk of out-of-hospital (OFH) death among the very advanced age (≥80 years) population. METHODS: We conducted a retrospective cohort investigation, involving internal medicine inpatients aged ≥80 years of age, who sought treatment at a teaching hospital in western China. We obtained OFH mortality information from telephonic interviews. Subsequently, we employed Cox proportional hazards models to analyze the links between AST/ALT and Cr/CysC*100 and OFH all-cause mortality among the very advanced age (≥80 years old) population. RESULTS: In all, we recruited 398 subjects, among which 51.51% were male. The median age of OFH deceased male patients was 85 years, and the same for female patients was 87 years. The total quantity of OFH deaths was 164 (41.21%). Among the oldest male population, those who died OFH exhibited enhanced AST/ALT, relative to those who survived (death vs. survival: 1.5 vs 1.3, P=0.008). However, among the oldest female, there was no difference in AST/ALT between patients who expired OFH, and those who survived. Among the oldest elders (male and female), Cr/CysC*100 did not significantly differ between surviving and OFH deceased patients. Additional analysis involving the Cox proportional hazards model revealed that among the oldest male population, an enhanced AST/ALT denoted an augmented risk of OFH death (hazard ratios (HRs) =1.797, 95%CI: 1.2-2.691). However, Cr/CysC*100 was not correlated with OFH mortality risk. Among the oldest female population, neither AST/ALT nor Cr/CysC*100 was correlated with OFH mortality risk. CONCLUSIONS: Enhanced AST/ALT was correlated with an augmented OFH mortality risk among the oldest male, but not female population. Alternately, Cr/CysC*100 was not linked to OFH mortality risk among any population.

Multi-omics Mendelian randomization integrating GWAS, eQTL, and mQTL data identified genes associated with breast cancer.

Breast cancer (BC) remains a major disease posing a threat to women's health, but the underlying biological interpretation remains largely unknown. Here, we aimed to identify genes associated with breast cancer and analyze their pathophysiological mechanisms based on multi-omics Mendelian randomization (MR). Summary-data-based MR (SMR) was performed to estimate the causal effects of blood and breast mammary tissue expression quantitative trait loci (eQTLs) on BC. External validation analysis was used to validate the identified genes. Integration analyses BC GWAS summaries with eQTLs and DNA methylation QTLs (mQTLs) from the blood were conducted using SMR to prioritize putative blood genes and their regulatory elements associated with BC risk. Finally, two prior genes (ATG10 and RCCD1) from blood tissue reached significant levels in both BCAC (ATG10: ORBRCR = 0.91, PBRCR = 1.29 × 10-11; RCCD1: ORBRCR = 0.90, PBRCR = 3.72 × 10-15) and FinnGen cohorts (ATG10: ORFinnGen = 0.89, PFinnGen = 8.55 × 10-5; RCCD1: ORFinnGen = 0.89, PFinnGen = 2.38 × 10-8). Additionally, those two genes from breast tissues also replicated in both BCAC (ATG10: ORBRCR = 0.95, PBRCR = 1.02 × 10-9; RCCD1: ORBRCR = 0.87, PBRCR = 4.70 × 10-10) and FinnGen cohorts (ATG10: ORFinnGen = 0.93, PFinnGen = 2.38 × 10-4; RCCD1: ORFinnGen = 0.85, PFinnGen = 3.81 × 10-6). Sensitive analysis and external validation analysis validated those two identified genes. Multi-omics MR analysis showed that the SNP signals associated with ATG10 and RCCD1 were significant across the data from BC Genome-wide association study (GWAS), eQTL, and mQTL studies. In conclusion, we identified two priority genes that are potentially associated with BC. These findings improve our limited understanding of the mechanism of BC and shed light on the development of therapeutic agents for treating BC.

Facile preparation of high-efficiency peroxidase mimics: modulation of the catalytic microenvironment of LDH nanozymes through defect engineering induced by amino acid intercalation.

Nanozymes have gained much attention as a replacement for natural enzymes duo to their unique advantages. Two-dimensional layered double hydroxide (LDH) nanomaterials with high physicochemical plasticity are emerging as the main forces for the construction of nanozymes. Unfortunately, high-performance LDH nanozymes are still scarce. Recently, defects in nanomaterials have been verified to play a significant role in modulating the catalytic microenvironment, thereby improving catalytic performances of nanozymes. Therefore, the marriage between defect engineering and LDH nanozymes is expected to spark new possibilities. In this work, twenty kinds of natural amino acids were separately inserted into the interlayer of CoFe-LDH to obtain defect-rich CoFe-LDH nanozymes. The peroxidase (POD)-like activity and catalytic mechanism of the as-prepared LDH nanozymes were systematically studied. The results showed that the intercalation of amino acids can effectively enhance the POD-like activity of LDH nanozymes owing to the increasing oxygen/metal vacancies. And l-cysteine intercalated LDH exhibited the highest catalytic activity ascribed to its thiol group. As a proof of concept, LDH nanozymes with superb POD-like activity were used in biosensing and antibacterial applications. This work suggests that modulating the catalytic microenvironment through defect engineering is an effective way to obtain high-efficiency POD mimics.

Engineering Logic DNA Nanoprobes on Live Cell Membranes for Simultaneously Monitoring Extracellular pH and Precise Drug Delivery.

It remains a challenge to use a single probe to simultaneously detect extracellular pH fluctuations and specifically recognize cancer cells for precise drug delivery. Here, we engineered a tetrahedral framework nucleic acid-based logic nanoprobe (isgc8-tFNA) on live cell membranes for simultaneously monitoring extracellular pH and targeted drug delivery. Isgc8-tFNA was anchored stably on the cell surface through three cholesterol molecules inserting into the bilayer of the cell membrane. Once responding to the acidic tumor microenvironment, isgc8-tFNA formed an i-motif structure, leading to turn-on FRET signals for monitoring changes of extracellular pH. The nanoprobe exhibited a narrow pH-response window and excellent reversibility. Moreover, the nanoprobe could execute logic identification on the cell surface for precise drug delivery. Only if both in the acidic microenvironment and aptamer-targeting marker are present on the cell surface, the sgc8-ASO-chimera strand, carrying an antisense oligonucleotide drug, was released from the nanoprobe and entered into targeted cancer cells for gene silence. Additionally, the in situ drug release facilitated the uptake of drugs mediated by the interaction between sgc8 aptamer and membrane proteins, resulting in enhanced inhibition of cancer cell migration and proliferation. This logic nanoprobe will provide inspiration for designing smart devices for diagnosis of pH-related diseases and targeted drug delivery.

Causal relationship between female reproductive factors, sex hormones and uterine leiomyoma: a Mendelian randomization study.

RESEARCH QUESTION: Are the observed associations between female reproductive factors and sex hormones with the risk of uterine leiomyoma truly causal associations? DESIGN: The putative causal relationships between female reproductive factors and sex hormones with uterine leiomyoma were investigated using two-sample Mendelian randomization. Statistics on exposure-associated genetic variants were obtained from genome-wide association studies (GWAS). The uterine leiomyoma GWAS from the FinnGen and FibroGENE consortia were used as outcome data for discovery and replication analyses, respectively. Results were pooled by meta-analysis. Sensitivity analyses ensured robustness of the Mendelian randomization analysis. RESULTS: When FinnGen GWAS were used as outcome data, a causal relationship was found between age at menarche (OR 0.84, P < 0.0001), age at menopause (OR 1.08, P < 0.0001), number of live births (OR 0.25, P < 0.001) and total testosterone levels (OR 0.90, P < 0.001) with the risk of uterine leiomyoma. When FibroGENE GWAS were used as outcome data, Mendelian randomization results for age at menopause, the number of live births and total testosterone levels were replicated. In the meta-analysis, a later age at menopause (OR 1.08, P < 0.0001) was associated with an increased risk of uterine leiomyoma. A higher number of live births (OR 0.25, P < 0.0001) and higher total testosterone levels (OR 0.90, P < 0.0001) were associated with a decreased risk of uterine leiomyoma. CONCLUSIONS: A causal relationship between later age at menopause, lower number of live births and lower total testosterone levels with increased risk of uterine leiomyoma was found.

Associations of 10 dietary habits with breast cancer: a Mendelian randomization study.

Introduction: Epidemiological studies have revealed a link between dietary habits and the breast cancer risk. The causality of the association between food consumption and breast cancer requires further investigation. Methods: Using Mendelian randomization, we assessed the causal effects of 10 dietary habits on the risks of breast cancer and its subtypes (estrogen receptor [ER] + and ER- breast cancer). We obtained dietary pattern data in 2018 (number of single-nucleotide polymorphisms [SNPs] = 9,851,867) and breast cancer data in 2017 (number of SNPs = 10,680,257) from IEU OpenGWAS. Rigorous sensitivity analyses were conducted to ensure that the study results were credible and robust. Results: We identified that genetic predisposition to higher dried fruit intake was linked to a reduced risk of overall breast cancer (inverse variance-weighted [IVW] odds ratio [OR] = 0.55; 95% confidence interval [CI]: 0.43-0.70; p = 1.75 × 10-6), ER+ breast cancer (IVW OR = 0.62; 95% CI: 0.47-0.82; p = 8.96 × 10-4) and ER- breast cancer (IVW OR = 0.48; 95% CI: 0.34-0.68; p = 3.18 × 10-5), whereas genetic predisposition to more oily fish intake was linked to a lower risk of ER+ breast cancer (IVW OR = 0.73; 95% CI: 0.53-0.99; p = 0.04). Discussion: Our findings suggest that a genetic predisposition for dried fruit and oily fish consumption may be protective against breast cancer; however, further investigation is required.

Quantitative detection of microRNA-21 in vivo using in situ assembled photoacoustic and SERS nanoprobes.

Accurately quantifying microRNA levels in vivo is of great importance for cancer staging and prognosis. However, the low abundance of microRNAs and interference from the complex tumor microenvironment usually limit the real-time quantification of microRNAs in vivo. Herein, for the first time, we develop an ultrasensitive microRNA (miR)-21 activated ratiometric nanoprobe for quantification of the miR-21 concentration in vivo without signal amplification as well as dynamic tracking of its distribution. The core-satellite nanoprobe by miR-21 triggered in situ self-assembly was built on nanogapped gold nanoparticles (AuNNP probe) and gold nanoparticles (AuNP probe). The AuNP probe generated a photoacoustic (PA) signal and ratiometric SERS signal with the variation of miR-21, whereas the AuNNP probe served as an internal standard, enabling ratiometric SERS imaging of miR-21. The absolute concentration of miR-21 in MCF-7 tumor-bearing mice was quantified to be 83.8 ± 24.6 pM via PA and ratiometric SERS imaging. Our strategy provides a powerful approach for the quantitative detection of microRNAs in vivo, providing a reference for the clinical treatment of cancer.

Diet-derived antioxidants and osteoporosis: A Mendelian randomization study.

BACKGROUND: Antioxidants can prevent osteoporosis, but the association between serum antioxidants and the cause of osteoporosis remains unknown. We aimed to utilize Mendelian randomization (MR) to determine whether genetically predicted serum levels of diet-derived antioxidants can affect the risk of osteoporosis, to determine the effect of dietary supplementation of antioxidants. METHODS: Genetic variants associated with diet-derived antioxidants were selected from the genome-wide association studies. A total of 12,946 osteoporosis cases and 506,624 healthy controls were obtained from UK Biobank (UKB) and Genetic Factors of Osteoporosis (GEFOS) consortia. We implemented a two-sample MR design and performed several sensitivity analyses to evaluate the causal relationship. RESULTS: In UKB, the genetically predicted higher ß-carotene (OR = 0.863, p = 7.37 × 10-6, power = 100%) and γ-tocopherol (OR = 0.701, p = 0.021, power = 5%) had an inverse relationship with osteoporosis. However, only the association of serum ß-carotene passed FDR correction. In GEFOS, there were no significant diet-derived antioxidants. The direction of the association of ß-carotene with osteoporosis (OR = 0.844, p = 0.106, power = 87%) was consistent with that in the UKB dataset. A fixed-effects meta-analysis confirmed that ß-carotene (OR = 0.862, p = 2.21 × 10-6) and γ-tocopherol (OR = 0.701, p = 2.31 × 10-2) could decrease the risk of osteoporosis. To reduce exclusion limit bias, we used total body bone mineral density, lumbar spine bone mineral density and femoral neck bone mineral density as surrogates and found that the genetically elevated circulating ß-carotene level could increase total body BMD (beta = 0.043, p-value = 8.26 x 10-5, power = 100%), lumbar spine BMD (beta = 0.226, p-value = 0.001, power = 100%) and femoral neck BMD(beta = 0.118, p-value = 0.016, power = 100%). CONCLUSIONS: We observed that genetically predicted serum ß-carotene could elevate BMD and prevent osteoporosis.

Causal pathways linking polycystic ovary syndrome to distinct breast cancer subtypes through mediator factors: a multivariable mendelian randomization analysis.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovarian cysts, high androgen levels, and irregular menstruation. The causality between PCOS and breast cancer (BC) has been widely discussed as they share a significant intersection in clinical manifestations. Previous epidemiological studies have not provided consistent conclusions in association between PCOS and BC, while mendelian randomization (MR) analyses have confirmed the causality between PCOS and estrogen receptor-positive breast cancer (ER + BC), but among a series of clinical manifestations resulting from PCOS, which related traits mediate the causal effect remains unknown. In this study, we conducted multivariable mendelian randomization (MVMR) analysis to explore the potential mediator variables in the mechanism linking PCOS to distinct subtypes of BC, and calculated the mediating effects proportion. We analyzed 13 PCOS-related traits and found that age at menopause may mediate PCOS-induced ER + BC (with -4.82% proportion) with a weak protective effect through the repair of DNA double-strand breaks by homologous recombination. This study helps to better comprehend the shared mechanisms contributing to the development of both PCOS and BC, and to screen high-risk populations for BC and take appropriate preventive measures.

Targeting Pyroptosis through Lipopolysaccharide-Triggered Noncanonical Pathway for Safe and Efficient Cancer Immunotherapy.

Inducing pyroptosis in cancer cells holds great potential in cancer immunotherapy. Lipopolysaccharide (LPS)-sensing noncanonical pathways are an important mechanism of pyroptosis to eliminate damaged cells, which has not yet been explored for cancer immunotherapy. Here, we utilize bacterial outer membrane vesicles (OMVs) as a natural LPS carrier to trigger a noncanonical pyroptosis pathway for immunotherapy. To address the concern of systemic toxicity, molecule engineered OMVs were designed by equipping DNA aptamers on the OMVs (Apt-OMVs). In addition to improving capacity to target tumors, Apt-OMVs also took advantage of the spherical nucleic acid structure to shield OMVs against nonspecific immune recognition and evade immunogenicity. The selective pyroptosis enhanced tumor immunogenicity, not only promoting the infiltration of effector T cells but also reducing the amount of immunosuppressive regulatory T cells, which remarkably suppressed tumor growth. This work reports the first pyroptosis inducer by the noncanonical pathway, offering inspiration for safe and efficient pyroptosis-mediated immunotherapy.

Genetic liability to multiple factors and uterine leiomyoma risk: a Mendelian randomization study.

Background and objective: Uterine leiomyoma is the most common benign tumor in females of reproductive age. However, its causes have never been fully understood. The objective of our study was to analyze the causal association between various factors and uterine leiomyoma using Mendelian randomization (MR). Methods: Genetic variables associated with risk factors were obtained from genome-wide association studies. Summary-level statistical data for uterine leiomyoma were obtained from FinnGen and the UK Biobank (UKB) consortium. We used inverse variance weighted, MR-Egger, and weighted median methods in univariate analysis. Multivariable MR analysis was used to identify independent risk factors. A fixed-effect model meta-analysis was used to combine the results of the FinnGen and UKB data. Results: In the FinnGen data, higher genetically predicted age at natural menopause, systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting insulin were associated with an increased risk of uterine leiomyoma, while higher age at menarche was associated with a reduced risk of uterine leiomyoma. Multivariable MR analysis of SBP and DBP showed that higher DBP might be an independent risk factor of uterine leiomyoma. In the UKB data, the results for age at natural menopause, SBP, DBP, and age at menarche were replicated. The result of the meta-analysis suggested that uterine leiomyoma could also be affected by polycystic ovary syndrome (PCOS), endometriosis, and 2-hour glucose level. Conclusion: Our MR study confirmed that earlier menstrual age, hypertension, obesity, and elevated 2-hour glucose post-challenge were risk factors for uterine leiomyoma, and the causal relationship between smoking and uterine leiomyoma was ruled out. In addition, later age of menopause and endometriosis were found to increase the risk of uterine leiomyoma, while PCOS was found to decrease the risk.

Postoperative infectious complications following laparoscopic versus open hepatectomy for hepatocellular carcinoma: a multicenter propensity score analysis of 3876 patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. PATIENTS AND METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). RESULTS: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study.

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS: The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.

Influence of deposition temperature on microstructure and gas-barrier properties of Al2O3 prepared by plasma-enhanced atomic layer deposition on a polycarbonate substrate.

We prepared polymer-based encapsulation films by plasma-enhanced atomic layer deposition (PEALD) of Al2O3 film on a polycarbonate (PC) substrate at 80-160 °C to fabricate Al2O3/PC barrier films. The thermal and dynamic mechanical properties of the PC substrate, the structural evolution of PEALD Al2O3 films, the optical transmission, surface morphology, and gas-barrier properties of Al2O3/PC film are all studied in this work as a function of temperature. The glass transition temperature T g of the PC substrate is about 140 °C, and the coefficient of thermal expansion increases significantly when the temperature exceeds T g. Increasing the deposition temperature from 80 to 160 °C for Al2O3 film deposited over 300 cycles increases the density from 3.24 to 3.45 g cm-3, decreases the thickness from 44 to 40 nm, and decreases the O/Al content ratio from 1.525 to 1.406. Al2O3/PC films deposited at 80-120 °C have no surface cracks, whereas surface cracks appear in samples deposited near or above 140 °C. Upon increasing the deposition temperature, the water vapor transmission rate (WVTR) and oxygen transmission rate (OTR) of Al2O3/PC films decrease significantly at temperatures below T g, and then increase at temperatures near to or above T g due to cracks in the films. The optimal deposition temperature is 120 °C, and the minimum WVTR and OTR of Al2O3/PC film are 0.00132 g per (m2 24 h) and 0.11 cm3 per (m2 24 h 0.1 MPa), respectively. The gas-barrier properties of the Al2O3/PC films are attributed to both the densification of the Al2O3 film and the cracks, which are caused by the shrinkage of the PC substrate.

A large-scale plasma proteome Mendelian randomization study identifies novel causal plasma proteins related to primary biliary cholangitis.

Background and aims: Primary biliary cholangitis (PBC) is a progressive chronic autoimmune cholestatic liver disease characterized by the destruction of small intrahepatic bile ducts leading to biliary cirrhosis. Liver biopsy is required in the diagnosis of Antimitochondrial antibody-negative patients. Therefore, novel biomarkers are needed for the non-invasive diagnosis of PBC. To identify novel biomarkers for PBC, we conducted large-scale plasma proteome Mendelian randomization (MR). Methods: A total of 21,593 protein quantitative trait loci (pQTLs) for 2297 circulating proteins were used and classified into four different groups. MR analyses were conducted in the four groups separately. Furthermore, the results were discovered and replicated in two different cohorts of PBC. Colocalization analysis and enrichment analysis were also conducted. Results: Three plasma proteins (ficolin-1, CD40 and protein FAM177A1) were identified and replicated as being associated with PBC. All of them showed significant protective effects against PBC. An increase in ficolin-1 (OR=0.890 [0.843-0.941], p=3.50×10-5), CD40 (OR=0.814 [0.741-0.895], p=1.96×10-5) and protein FAM177A1 (OR=0.822 [0.754-0.897], p=9.75×10-6) reduced the incidence of PBC. Ficolin-1 (PP4 = 0.994) and protein FAM177A1 (PP4 = 0.995) colocalized with the expression of the genes FCN1 and FAM177A1 in whole blood, respectively. Furthermore, CD40 (PP4 = 0.977) and protein FAM177A1 (PP4 = 0.897) strongly colocalized with PBC. Conclusions: We expand the current biomarkers for PBC. In total, three (ficolin-1, CD40, and protein FAM177A1) plasma proteins were identified and replicated as being associated with PBC in MR analysis. All of them showed significant protective effects against PBC. These proteins can be potential biomarkers or drug targets for PBC.

Design and Synthesis of SERS Materials for In Vivo Molecular Imaging and Biosensing.

Surface-enhanced Raman scattering (SERS) is a feasible and ultra-sensitive method for biomedical imaging and disease diagnosis. SERS is widely applied to in vivo imaging due to the development of functional nanoparticles encoded by Raman active molecules (SERS nanoprobes) and improvements in instruments. Herein, the recent developments in SERS active materials and their in vivo imaging and biosensing applications are overviewed. Various SERS substrates that have been successfully used for in vivo imaging are described. Then, the applications of SERS imaging in cancer detection and in vivo intraoperative guidance are summarized. The role of highly sensitive SERS biosensors in guiding the detection and prevention of diseases is discussed in detail. Moreover, its role in the identification and resection of microtumors and as a diagnostic and therapeutic platform is also reviewed. Finally, the progress and challenges associated with SERS active materials, equipment, and clinical translation are described. The present evidence suggests that SERS could be applied in clinical practice in the future.

Novel Causal Plasma Proteins for Hypothyroidism: A Large-scale Plasma Proteome Mendelian Randomization Analysis.

CONTEXT: Although several risk proteins for hypothyroidism have been reported in recent years, many more plasma proteins have not been tested. OBJECTIVE: To determine potential mechanisms and novel causal plasma proteins for hypothyroidism using Mendelian randomization (MR). METHODS: A large-scale plasma proteome MR analysis was conducted using protein quantitative trait loci (pQTLs) for 2297 plasma proteins. We classified pQTLs into 4 different groups. MR analyses were conducted within the 4 groups simultaneously. Significant proteins were discovered and validated in 2 different cohorts. Colocalization analysis and enrichment analysis were conducted using proteins found with MR. RESULTS: Thirty-one proteins were identified in the discovery cohort. Among them, 13 were validated in the validation cohort. Nine of the 13 proteins are risk factors (ISG15, Fc receptor-like protein 2, tumor necrosis factor ligand superfamily member 14, Rab-2A, FcRL3, thrombomodulin, interferon [IFN]-lambda-1, platelet glycoprotein Ib alpha chain, IL-7RA) for hypothyroidism, whereas others are protective proteins (protein O-glucosyltransferase 1 [POGLUT1], tumor necrosis factor ligand superfamily, 3-hydroxyisobutyryl-CoA hydrolase, transferrin receptor protein 1). Among the significant proteins, POGLUT1 strongly colocalized with expression quantitative trait loci from whole blood (posterior probability of colocalization [PP4] = 0.978) and the thyroid (PP4 = 0.978). Two different trans-pQTLs (rs2111485 PP4 = 0.998; rs35103715 PP4 = 0.998) for IFN-lambda-1 strongly colocalized with hypothyroidism in different chromosomes. CONCLUSION: Thirteen various proteins were identified and validated to be associated with hypothyroidism using univariable MR. We reinforced and expanded the effect of IFN on hypothyroidism. Several proteins identified in this study could explain part of the association between the coagulation system and hypothyroidism. Our study broadens the causal proteins for hypothyroidism and provides the relationships between plasma proteins and hypothyroidism. The proteins identified in this study can be used as early screening biomarkers for hypothyroidism.

Hydrogen-bond-driven self-assembly of chemiluminophore affording long-lasting in vivo imaging.

Developing chemiluminescence probe with a slow kinetic profile, even a constant emission within analytical time, would improve the analytical sensitivity, but still remains challenging. This work reports a novel strategy to afford long-lasting in vivo imaging by developing a self-assembled chemiluminophore HPQCL-Cl via the introduction of the hydrogen-bond-driven self-assembled dye HPQ to Schaap's dioxetane. Compared with classical chemiluminophore HCL, self-assembled HPQCL-Cl was isolated from the physiological environment, thereby lowering its deprotonation and prolonging its half-life. Based on HPQCL-Cl, the long-lasting in vivo imaging of 9L-lacz tumor was achieved by developing a ß-gal-responsive probe. Its signals remained constant (<5% change) for about 20 min, which may provide a wide time window for the determination of ß-gal. This probe also showed high tumor-to-normal tissue ratio throughout tumor resection, highlighting its potential in image-guided clinical surgery.