Digital colloid-enhanced Raman spectroscopy for the pharmacokinetic detection of bioorthogonal drugs.

Bioorthogonal drug molecules are currently gaining prominence for their excellent efficacy, safety and metabolic stability. Pharmacokinetic study is critical for understanding their mechanisms and guiding pharmacotherapy, which is primarily performed with liquid chromatography-mass spectrometry as the gold standard. For broader and more efficient applications in clinics and fundamental research, further advancements are especially desired in cheap and portable instrumentation as well as rapid and tractable pretreatment procedures.

Fluorescent Pdots Facilitate High-Resolution Mapping of the Intact Meningeal Vascular Network and Eye-Brain Connections.

Meningeal vascular network is significant in neurology and neurosurgery. However, high-resolution imaging of intact meningeal vascular network is lacking. In this work, we develop a practical experimental method to ensure that the intact meninges are morphologically unfolded and fixed in an agarose gel.

Discovery of as a new gene underpinning congenital heart defects.

Objective: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in -knockout animals. The objective of this retrospective study was to identify a new mutation responsible for CHD and characterize the functional effect of the identified CHD-causing mutation.

Nanoparticle-based applications by atmospheric pressure matrix assisted desorption/ionization mass spectrometry.

Recently, the development of atmospheric pressure matrix assisted desorption/ionization mass spectrometry (AP MALDI MS) has made contributions not only to biomolecule analysis but also to spatial distribution. This has positioned AP MALDI as a powerful tool in multiple domains, thanks to its comprehensive advantages compared to conventional MALDI MS. These developments have addressed challenges associated with previous AP MALDI analysis systems, such as optimization of apparatus settings, synthesis of novel matrices, preconcentration and isolation strategies before analysis.

Engineering of antimicrobial peptide fibrils with feedback degradation of bacterial-secreted enzymes.

Proteins and peptides can assemble into functional amyloid fibrils with distinct architectures. These amyloid fibrils can fulfil various biological functions in living organisms, and then be degraded. By incorporating an amyloidogenic segment and enzyme-cleavage segment together, we designed a peptide (enzyme-cleavage amyloid peptides (EAP))-based functional fibril which could be degraded specifically by gelatinase.

[Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification].

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction.

NAD administration profoundly decreases UVC-induced skin damage by attenuating oxidative stress, inflammation, DNA damage and apoptosis.

Ultraviolet (UV) radiation is a major cause of multiple major skin diseases including skin cancer. It is crucial to discover new agents that can produce profound protective effects on UV-produced skin damage. Using a mouse model, in this study we determined the effects of NAD on UVC-induced skin damage and investigated the mechanisms underlying the effects, obtaining the following discoveries: First, UVC-induced skin's green autofluorescence (AF) was highly correlated with the extent of UVC-indued skin's damage; second, NAD administration profoundly decreased UVC-induced skin damage; third, NAD administration significantly attenuated UVC-induced decreases in the levels of mitochondrial superoxide dismutase and catalase; fourth, NAD administration significantly attenuated UVC-induced increase in the level of cyclooxygenase (COX) 2 - a marker of inflammation; fifth, NAD administration profoundly attenuated UVC-induced increase in double-strand DNA (dsDNA) damage; and sixth, NAD administration profoundly attenuated UVC-induced decreases in the ratios of Bcl-2/Bax - an index of apoptosis.

Molecular dynamics simulation insights into the cellular uptake of elastic nanoparticles through human pulmonary surfactant.

The interaction between inhaled nanoparticles (NPs) and the pulmonary surfactant (PS) monolayer has drawn significant attention due to its potential in drug delivery design and application for respiratory therapeutics in active and passive cellular uptake pathways. Even though much attention has been given to explore the interaction between NPs and the PS monolayer, the effects of the NP elasticity on the translocation across the PS monolayer have not been thoroughly studied. Here, we performed a series of coarse-grained (CG) molecular dynamics simulations to study active or passive cellular uptake pathways of three NPs with different elasticities through a PS monolayer.

A smartphone-based three-in-one biosensor for co-detection of SARS-CoV-2 viral RNA, antigen and antibody.

Rapid and comprehensive diagnostic methods are necessary for early identification and monitoring of SARS-CoV-2. Here, we have developed a universal and portable three-in-one biosensor linked to a smartphone for co-detection of SARS-CoV-2 viral RNA, antigen, and antibody. In combination with a smartphone, the online monitoring of SARS-CoV-2 virus-infected patients from infection to immunization could be intelligently achieved.

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD-ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective.

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.

Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to disrupt the RBD-hACE2 complex using molecular screening and simulation approaches.

A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.

SOX7 loss-of-function variation as a cause of familial congenital heart disease.

Introduction: As the most frequent type of birth defect in humans, congenital heart disease (CHD) leads to a large amount of morbidity and mortality as well as a tremendous socioeconomic burden. Accumulating studies have convincingly substantiated the pivotal roles of genetic defects in the occurrence of familial CHD, and deleterious variations in a great number of genes have been reported to cause various types of CHD. However, owing to pronounced genetic heterogeneity, the hereditary components underpinning CHD remain obscure in most cases.

2'--Methyl modified guide RNA promotes the single nucleotide polymorphism (SNP) discrimination ability of CRISPR-Cas12a systems.

The CRISPR-Cas12a system has been widely applied to genome editing and molecular diagnostics. However, off-target cleavages and false-positive results remain as major concerns in Cas12a practical applications. Herein, we propose a strategy by utilizing the 2'--methyl (2'-OMe) modified guide RNA (gRNA) to promote the Cas12a's specificity.

Dose-Dependent Carbon-Dot-Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized.

Hairpin-Spacer crRNA-Enhanced CRISPR/Cas13a System Promotes the Specificity of Single Nucleotide Polymorphism (SNP) Identification.

The Cas13a system has great potential in RNA interference and molecular diagnostic fields. However, lacking guidelines for crRNA design hinders practical applications of the Cas13a system in RNA editing and single nucleotide polymorphism identification. This study posits that crRNAs with hairpin spacers improve the specificity of CRISPR/Cas13a system (termed hs-CRISPR).

AZD9291 Resistance Reversal Activity of a pH-Sensitive Nanocarrier Dual-Loaded with Chloroquine and FGFR1 Inhibitor in NSCLC.

AZD9291 can effectively prolong survival of non-small cell lung cancer (NSCLC) patients. Unfortunately, the mechanism of its acquired drug resistance is largely unknown. This study shows that autophagy and fibroblast growth factor receptor 1 signaling pathways are both activated in AZD9291 resistant NSCLC, and inhibition of them, respectively, by chloroquine (CQ) and PD173074 can synergistically reverse AZD9291 resistance.

A computational perspective on the dynamic behaviour of recurrent drug resistance mutations in the pncA gene from .

Tuberculosis is still one of the top 10 causes of death worldwide, particularly with the emergence of multidrug-resistant tuberculosis. As the most effective first-line anti-tuberculosis drug, pyrazinamide also develops resistance due to the mutation in the pncA gene. Among these mutations, seven mutations at positions F94L, F94S, K96N, K96R, G97C, G97D, and G97S are classified as high-level resistance mutations.

Rapid Computer-Aided Diagnosis of Stroke by Serum Metabolic Fingerprint Based Multi-Modal Recognition.

Stroke is a leading cause of mortality and disability worldwide, expected to result in 61 million disability-adjusted life-years in 2020. Rapid diagnostics is the core of stroke management for early prevention and medical treatment. Serum metabolic fingerprints (SMFs) reflect underlying disease progression, predictive of patient phenotypes.

Diagnosis and prognosis for exercise-induced muscle injuries: from conventional imaging to emerging point-of-care testing.

With the development of modern society, we have witnessed a significant increase of people who join in sport exercises, which also brings significantly increasing exercise-induced muscle injuries, resulting in reduction and even cessation of participation in sports and physical activities. Although severely injured muscles can hardly realize full functional restoration, skeletal muscles subjected to minor muscle injuries (, tears, lacerations, and contusions) hold remarkable regeneration capacity to be healed without therapeutic interventions. However, delayed diagnosis or inappropriate prognosis will cause exacerbation of the injuries.

Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention.

In 2019/2020, the emergence of coronavirus disease 2019 (COVID-19) resulted in rapid increases in infection rates as well as patient mortality. Treatment options addressing COVID-19 included drug repurposing, investigational therapies such as remdesivir, and vaccine development. Combination therapy based on drug repurposing is among the most widely pursued of these efforts.

Sequential PDT and PTT Using Dual-Modal Single-Walled Carbon Nanohorns Synergistically Promote Systemic Immune Responses against Tumor Metastasis and Relapse.

Immune responses stimulated by photodynamic therapy (PDT) and photothermal therapy (PTT) are a promising strategy for the treatment of advanced cancer. However, the antitumor efficacy by PDT or PTT alone is less potent and unsustainable against cancer metastasis and relapse. In this study, Gd and chlorin e6 loaded single-walled carbon nanohorns (Gd-Ce6@SWNHs) are developed, and it is demonstrated that they are a strong immune adjuvant, and have high tumor targeting and penetration efficiency.

Biomechanical differences before and after arthroscopic partial meniscectomy in patients with semilunar and discoid lateral meniscus injury.

The purpose of the current study was to investigate the differences in knee kinematics and kinetics in patients with semilunar lateral meniscus (SLM) and discoid lateral meniscus (DLM) injuries before and after arthroscopic partial meniscectomy during level walking. Fifteen healthy volunteers (control group), thirteen patients with SLM injury (SLM group) and nine patients with DLM injury (DLM group) were enrolled in our study. Gait analyses were performed pre- and post-operatively during level walking at a self-selected walking speed.

Predictive values of the ratio of beta-human chorionic gonadotropin for failure of salpingostomy in ectopic pregnancy.

Background: We evaluated the predictors of unsuccessful salpingostomy that required surgical treatment or additional medical treatment after initial removal of ectopic pregnancy (EP) by laparoscopy.

Material/methods: The study was an observational retrospective cohort study done at International Peace Maternity and Child Health Hospital in Shanghai, which included patients with ectopic pregnancy (EP). The predictors of persistent ectopic pregnancy (PEP) were measured either on serum β-hCG ratios before and after salpingostomy or demographics (age, parity, in-vitro fertilization (IVF), abortion history, EP history, mass location, appendectomy history and diameter of EP lesion).

Circulating DNA-Based Sequencing Guided Anlotinib Therapy in Non-Small Cell Lung Cancer.

Anlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non-small cell lung cancer (NSCLC) patients is still elusive. Here, tumor-specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of and genetic profiling.