M6A RNA methylation-mediated dysregulation of AGAP2-AS1 promotes trastuzumab resistance of breast cancer.

INTRODUCTION: Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer patients, but its efficacy is often limited by chemotherapy resistance. Recent studies indicate that long noncoding RNAs (lncRNAs) play important roles in tumor progression and response to therapy. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is still unknown to date. METHODS: qPCR was performed to detect the expression of related genes. Western blot and immunofluorescence assays were used for the evaluation of protein expression levels. A series of gain- or loss-functional assays confirmed the function of AGAP2-AS1 in trastuzumab resistance, both in vitro and in vivo. RNA immunoprecipitation and pulldown analysis was conducted to verify the interaction between METTL3/YTHDF2 and lncRNA AGAP2-AS1. , Results: AGAP2-AS1 was upregulated in trastuzumab-resistant cells and SKBR-3R-generated xenograft in nude mice. Silence of AGAP2-AS1 significantly decreased trastuzumab-induced cell cytotoxicity both in vitro and in vivo. The m6A methylation of AGAP2-AS1 was found to be reduced in trastuzumab resistant cells compared to parental cells. In addition, METTL3 increased the m6A methylation of AGAP2-AS1, which finally induced the suppression of AGAP2-AS1 expression. Moreover, YTHDF2 was essential for METTL3-mediated m6A methylation of AGAP2-AS1. Functionally, AGAP2-AS1 regulated trastuzumab resistance via inducing autophagy and increasing ATG5 protein level. CONCLUSION: Taken together, we proved that METTL3/YTHDF2-mediated m6A methylation indued the increased expression AGAP2-AS1, which could promote the trastuzumab resistance of breast cancer. In addition, AGAP2-AS1 also regulates trastuzumab resistance via inducing autophagy. Therefore, AGAP2-AS1 may be promising predictive biomarker and therapeutic target breast cancer patients.

A wireless controlled robotic insect with ultrafast untethered running speeds.

Running speed degradation of insect-scale (less than 5 cm) legged microrobots after carrying payloads has become a bottleneck for microrobots to achieve high untethered locomotion performance. In this work, we present a 2-cm legged microrobot (BHMbot, BeiHang Microrobot) with ultrafast untethered running speeds, which is facilitated by the complementary combination of bouncing length and bouncing frequency in the microrobot's running gait. The untethered BHMbot (2-cm-long, 1760 mg) can achieve a running speed of 17.5 BL s-1 and a turning centripetal acceleration of 65.4 BL s-2 at a Cost of Transport of 303.7 and a power consumption of 1.77 W. By controlling its two front legs independently, the BHMbot demonstrates various locomotion trajectories including circles, rectangles, letters and irregular paths across obstacles through a wireless control module. Such advancements enable the BHMbot to carry out application attempts including sound signal detection, locomotion inside a turbofan engine and transportation via a quadrotor.

The abnormalities of lipid metabolism in children and adolescents with major depressive disorder and relationship with suicidal ideation and attempted suicide.

Background: Major depressive disorder (MDD) is a widespread health issue in many countries, which has an extremely negative impact on the health of children and adolescents in particular. In the context of depression and metabolic disorders, dyslipidemia and metabolism-related problems become more prominent comorbidities. However, they continue to be the main barrier to the successful recovery of the clinical progress. In this study we investigated the rate of dyslipidemia, additional risk factors among Chinese children and adolescents with MDD, and association of the suicidal behavior with lipid levels. Methods: The study took 756 people from the Third People's Hospital of Fuyang between January 2020 and December 2021, aged between 8 and 18, with major depressive disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We determined the FBG (fasting blood glucose) and lipid parameters in all subjects and also investigated the history of suicidal ideation, the cases of attempted suicide, and the scores of depressive symptoms. Sociodemographic and clinical data were gathered and analyzed using the SPSS-23.0 version. Results: The prevalence of hypercholesterolemia, hypertriglyceridemia, high LDL-C, and low HDL-C were 5.42 % (41/756), 10.58 % (80/756), 3.84 % (29/756) and 5.42 % (41/756) respectively. For hypercholesterolemia and hypertriglyceridemia, they were positive associated with suicidal ideation and suicide attempts, and the positive correlation is shown between low HDL-C levels and suicide attempts. Nevertheless, non-ideation and inversely suicidal attempts were not discovered among high-LDL-C subjects. Logistic analysis showed that high levels of FBG (OR = 2.86, 95 % CI: 1.31-6.25, P = 0.008) and worse LDL-C (OR = 357.82, 95 % CI: 66.16-1935.10, P < 0.001) are the independent associated factors for hypercholesterolemia. More hospitalizations (OR = 1.89, 95 % CI: 1.07-3.35, P = 0.028), obesity (OR = 2.55, 95 % CI: 1.25-5.18, P = 0.010), high levels of TC (OR = 2.15, 95 % CI: 1.03-4.48, P = 0.042), and higher doses of antidepressants (OR = 1.02, 95 % CI: 1.00-1.04, P = 0.029) were independently associated factors for hypertriglyceridemia, while high levels of HDL-C (OR = 0.11, 95 % CI: 0.04-0.31, P < 0.001) were protective factors. In addition, high levels of TC (OR = 113.94, 95 % CI: 20.01-648.85) were statistically different (P < 0.001) and suggested that the factor was significantly related to high LDL-C. Meanwhile, older age (OR = 1.25, 95 % CI: 1.02-1.52, P = 0.030) and high levels of TG (OR = 3.00, 95 % CI: 1.98-4.55, P < 0.001) were independent factors contributing to low HDL-C. Conclusion: The high prevalence of dyslipidemia in childhood and adolescence among children and adolescents with depressive disorder has become a public health issue. Hypercholesterolemia and hypertriglyceridemia showed a positive correlation with suicidal thoughts and suicidal attempts. Monitoring the incidence of suicidal thoughts and attempts among them would carry some predictor meaning in therapy and for jumping back to health.

Ultrasonic controllable synthesis of sulfur-functionalized metal-organic frameworks (S-MOFs) and their application in piezo-photocatalytic rapid reduction of hexavalent chromium (Cr).

The United Nations' Sustainable Development Goals (SDGs) are significant in guiding modern scientific research. In recent years, scholars have paid much attention to MOFs materials as green materials. However, piezo catalysis of MOFs materials has not been widely studied. Piezoelectric materials can convert mechanical energy into electrical energy, while MOFs are effective photocatalysts for removing pollutants. Therefore, it is crucial to design MOFs with piezoelectric properties and photosensitivity. In this study, sulfur-functionalized metal-organic frameworks (S-MOFs) were prepared using organic sulfur-functionalized ligand (H2TDC) ultrasonic synthesis to enhance their piezoelectric properties and visible light absorption. The study demonstrated that the S-MOFs significantly enhanced the reduction of a 10 mg/L solution of hexavalent chromium to 99.4 % within 10 min, using only 15 mg of catalyst. The orbital energy level differences of the elements were analyzed using piezo response force microscopy (PFM) and X-ray photoelectron spectroscopy (XPS). The results showed that MOFs functionalized with sulfur atom ligands have a built-in electric field that facilitates charge separation and migration. This study presents a new approach to enhance the piezoelectric properties of MOFs, which broadens their potential applications in piezo catalysis and piezo-photocatalysis. Additionally, it provides a sustainable method for reducing hexavalent chromium, contributing to the achievement of sustainable development goals, specifically SDG-6, SDG-7, SDG-9, and SDG-12.

Progressive enhanced photodynamic therapy and enhanced chemotherapy fighting against malignant tumors with sequential drug release.

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.

Causal association of blood cell traits with inflammatory bowel diseases: a Mendelian randomization study.

Background: Observational studies have found associations between blood cell traits and inflammatory bowel diseases (IBDs), whereas the causality and dose-effect relationships are still undetermined. Methods: Two-sample Mendelian randomization (MR) analyses using linear regression approaches, as well as Bayesian model averaging (MR-BMA), were conducted to identify and prioritize the causal blood cell traits for Crohn's disease (CD) and ulcerative colitis (UC). An observational study was also performed using restricted cubic spline (RCS) to explore the relationship between important blood cell traits and IBDs. Results: Our uvMR analysis using the random effects inverse variance weighted (IVW) method identified eosinophil (EOS) as a causal factor for UC (OR = 1.36; 95% CI: 1.13, 1.63). Our MR-BMA analysis further prioritized that high level of lymphocyte (LYM) decreased CD risk (MIP = 0.307; θ^MACE = -0.059; PP = 0.189; θ^λ = -0.173), whereas high level of EOS increased UC risk (MIP = 0.824; θ^MACE = 0.198; PP = 0.627; θ^λ = 0.239). Furthermore, the observational study clearly depicts the nonlinear relationship between important blood cell traits and the risk of IBDs. Conclusion: Using MR approaches, several blood cell traits were identified as risk factors of CD and UC, which could be used as potential targets for the management of IBDs. Stratified genome-wide association studies (GWASs) based on the concentration of traits would be helpful owing to the nonlinear relationships between blood cell traits and IBDs, as demonstrated in our clinical observational study. Together, these findings could shed light on the clinical strategies applied to the management of CD and UC.

Optimization and Local Cost-Effectiveness of Nasopharyngeal Carcinoma Screening Strategies in Southern China: Secondary Analysis of the Guangdong Randomized Trial.

BACKGROUND: Screening with anti-Epstein-Barr Virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. METHODS: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women age 30-69). Seropositive subjects were rescreened annually for five years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial sub-cohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. RESULTS: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per-capita). Screening for 5-15 years between ages 35-59 met a willingness-to-pay threshold of 1.5 GDP/QALY in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One lifetime screen could reduce NPC mortality by pproximately 20%. CONCLUSIONS: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. IMPACT: These findings support population-based screening in southern China by defining the target population, cost effectiveness, and optimized screening approach.

Endocrine-Disrupting Chemical Exposure Induces Adverse Effects on the Population Dynamics of the Indo-Pacific Humpback Dolphin.

Cetaceans play a pivotal role in maintaining the ecological equilibrium of ocean ecosystems. However, their populations are under global threat from environmental contaminants. Various high levels of endocrine-disrupting chemicals (EDCs) have been detected in cetaceans from the South China Sea, such as the Indo-Pacific humpback dolphins in the Pearl River Estuary (PRE), suggesting potential health risks, while the impacts of endocrine disruptors on the dolphin population remain unclear. This study aims to synthesize the population dynamics of the humpback dolphins in the PRE and their profiles of EDC contaminants from 2005 to 2019, investigating the potential role of EDCs in the population dynamics of humpback dolphins. Our comprehensive analysis indicates a sustained decline in the PRE humpback dolphin population, posing a significant risk of extinction. Variations in sex hormones induced by EDC exposure could potentially impact birth rates, further contributing to the population decline. Anthropogenic activities consistently emerge as the most significant stressor, ranking highest in importance. Conventional EDCs demonstrate more pronounced impacts on the population compared to emerging compounds. Among the conventional pollutants, DDTs take precedence, followed by zinc and chromium. The most impactful emerging EDCs are identified as alkylphenols. Notably, as the profile of EDCs changes, the significance of conventional pollutants may give way to emerging EDCs, presenting a continued challenge to the viability of the humpback dolphin population.

Identification and expression analysis of XIP gene family members in rice.

Xylanase inhibitor proteins (XIP) are widely distributed in the plant kingdom, and also exist in rice. However, a systematic bioinformatics analysis of this gene family in rice (OsXIP) has not been conducted to date. In this study, we identified 32 members of the OsXIP gene family and analyzed their physicochemical properties, chromosomal localization, gene structure, protein structure, expression profiles, and interaction networks. Our results indicated that OsXIP genes exhibit an uneven distribution across eight rice chromosomes. These genes generally feature a low number of introns or are intronless, all family members, except for OsXIP20, contain two highly conserved motifs, namely Motif 8 and Motif 9. In addition, it is worth noting that the promoter regions of OsXIP gene family members feature a widespread presence of abscisic acid response elements (ABRE) and gibberellin response elements (GARE-motif and TATC-box). Quantitative Real-time PCR (qRT-PCR) analysis unveiled that the expression of OsXIP genes exhibited higher levels in leaves and roots, with considerable variation in the expression of each gene in these tissues both prior to and following treatments with abscisic acid (ABA) and gibberellin (GA3). Protein interaction studies and microRNA (miRNA) target prediction showed that OsXIP engages with key elements within the hormone-responsive and drought signaling pathways. The qRT-PCR suggested osa-miR2927 as a potential key regulator in the rice responding to drought stress, functioning as tissue-specific and temporally regulation. This study provides a theoretical foundation for further analysis of the functions within the OsXIP gene family.

Associations Between ABO Blood Groups and Diseases in the Digestive System and Vein.

Purpose: The ABO blood type system is crucial for human blood transfusions. However, the relationships between ABO blood groups and diseases in the digestive system and vein have not been elucidated. We investigated the relationships between ABO blood groups and diseases in the digestive system and vein in this study. Patients and Methods: A retrospective study on a Chinese population, including 1432 Crohn's disease (CD), 416 ulcerative colitis (UC), 1140 stomach cancer (SC), 841 colorectal cancer (CRC), 384 pancreatic cancer (PC), 520 liver cancer (LC), and 563 venous thrombosis (VT) patients, was performed. Furthermore, 896 healthy subjects were enrolled as normal controls (NC) in this study. The demographic characteristics of patients and NC were compared using the unpaired t-test and χ2 test. Multivariate logistic regression model was used to evaluate the association between ABO blood groups and CD and VT. Results: ABO blood groups distributions in UC, SC, CRC, PC, and LC patients did not differ from that of NC, but CD and VT patients had significant difference of ABO blood group distribution from that of NC (p = 0.015 and p = 0.002, respectively). Patients with CD and VT had considerably lower rates of type O blood (p = 0.011 and p = 0.001, respectively) and significantly higher rates of type AB blood (p = 0.013 and p = 0.022, respectively) than those with NC. Multivariate logistic regression analysis showed the association of CD and VT with non-O blood types was still significant with a higher risk than with blood group O after adjusting for age and gender (OR = 1.355, 95% CI = 1.100-1.670, p = 0.004 and OR = 1.465, 95% CI = 1.131-1.903, p = 0.004, respectively). Conclusion: ABO blood groups distributions in CD and VT patients significantly differed from that of NC. Non-O blood group could be a new predictor for CD and VT.

Heat-Localized and Salt-Resistant 3D Hierarchical Porous Ceramic Platform for Efficient Solar-Driven Interfacial Evaporation.

Solar-driven interfacial evaporation (SDIE) is a highly promising approach to achieve sustainable desalination and tackle the global freshwater crisis. Despite advancements in this field, achieving balanced thermal localization and salt resistance remains a challenge. Herein, the study presents a 3D hierarchical porous ceramic platform for SDIE applications. The utilized alumina foam ceramics (AFCs) exhibit remarkable corrosion resistance and chemical stability, ensuring a prolonged operational lifespan in seawater or brines. The millimeter-scale air-filled pores in AFCs prevent thermal losses through conduction with bulk water, resulting in heat-localized interfaces. The hydrophilic nature of macroporous AFC skeletons facilitates rapid water replenishment on the evaporating surface for effective salt-resistant desalination. Benefiting from its self-radiation adsorption and side-assisted evaporation capabilities, the AFC-based evaporators exhibit high indoor evaporation rates of 2.99 and 3.54 kg m-2 h-1 under one-sided and three-sided illumination under 1.0 sun, respectively. The AFC-based evaporator maintains a high evaporation rate of ≈2.77 kg m-2 h-1 throughout the 21-day long-term test. Furthermore, it achieves a daily water productivity of ≈10.44 kg m-2 in outdoor operations. This work demonstrates the potential of 3D hierarchical porous ceramics in addressing the trade-off between heat localization and salt resistance, and contributes to the development of durable solar steam generators.

Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA.

PURPOSE: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. METHODS: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA. RESULTS: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C. CONCLUSIONS: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

Preventing thermal aggregation of ovalbumin through dielectric-barrier discharge plasma treatment and enhancing its emulsification properties.

The impact of Dielectric-Barrier Discharge (DBD) plasma treatment on the prevention of heat-induced aggregation of Ovalbumin (OVA) and improvement in emulsification properties was investigated. Results highlighted the effective inhibition of thermal aggregation of OVA following exposure to plasma. Structural analysis revealed that the plasma-induced oxidation of sulfhydryl and intermolecular disulfide bonds played a pivotal role in inhibiting the thermal aggregation, considered by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), multiplies spectroscopy, and analysis of dynamic exchange of sulfhydryl-disulfide bonds. Meanwhile, the oxidation of exposed hydrophobic sites due to plasma treatment resulted in the transformation of the OVA molecule's surface from hydrophobic to hydrophilic, contributing significantly to the aggregation inhibition. Additionally, compared to an untreated sample of OVA, almost one-fold increase in emulsifying ability (EAI) and 1.5-fold in emulsifying stability (ESI) was observed after 4 min of plasma treatment. These findings demonstrated that plasma treatment not only enhanced the thermal stability of OVA, but also improved its emulsification properties.

Abnormal biochemical indicators of neonatal inherited metabolic disease in carriers.

BACKGROUND: Traditional biochemical screening for neonatal inherited metabolic diseases has high false-positive rates and low positive predictive values, which are not conducive to early diagnosis and increase parents' anxiety. This study analysed the relationship between gene variant carriers and their biochemical indicators in traditional biochemical screening, aiming to find explanations for false positives in newborns. RESULTS: This retrospective study included 962 newborns. Newborns underwent traditional biochemical screening at birth using blood staining and genomic sequencing of their stored blood staining using the NeoSeq Pro panel, which was able to detect 154 pathogenic genes and 86 diseases. A total of 632 newborns were carriers of gene variants. 56% of congenital hypothyroidism carriers had higher thyroid-stimulating hormone levels than normal newborns. Abnormal biochemical indices were detected in 71% of carriers of organic acid metabolic diseases, 69% of carriers of amino acid metabolic diseases, and 85% of carriers of fatty acid ß oxidation disorders. In carriers associated with organic acid metabolic diseases, the propionylcarnitine (C3), C3/acetylcarnitine (C2), and methylmalonylcarnitine (C4DC) + 3-hydroxyisovalerylcarnitine (C5OH) levels were higher than those in non-carriers (C3: 4.12 vs. 1.66 µmol/L; C3/C2: 0.15 vs. 0.09; C4DC + C5OH: 0.22 vs. 0.19 µmol/L). In carriers associated with amino acid metabolic diseases, phenylalanine levels were higher than those in non-carriers (68.00 vs. 52.05 µmol/L). For carriers of fatty acid ß oxidation disorders, butyrylcarnitine levels were higher than those in non-carriers (0.31 vs. 0.21 µmol/L), while the free carnitine levels were lower than those in non-carriers (14.65 vs. 21.87 µmol/L). There was a higher occurrence of carriers among newborns who received false-positive results for amino acid metabolic diseases compared to those who received negative results (15.52% vs. 6.71%). Similarly, there was a higher occurrence of carriers among newborns who received false-positive results for fatty acid ß oxidation disorders compared to those who received negative results (28.30% vs. 7.29%). CONCLUSIONS: This study showed that the carriers comprised a large number of newborns. Carriers had abnormal biochemical indicators compared with non-carriers, which could explain the false-positive rate for newborns using traditional newborn biochemical screening, especially in amino acid metabolic and fatty acid ß oxidation disorders.

Circulating DNA genome-wide fragmentation in early detection and disease monitoring of hepatocellular carcinoma.

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC.

Restoring T and B cell generation in X-linked severe combined immunodeficiency mice through hematopoietic stem cells adenine base editing.

Base editing of hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematologic diseases. However, the feasibility of using adenine-base-edited HSPCs for treating X-linked severe combined immunodeficiency (SCID-X1), the influence of dose-response relationships on immune cell generation, and the potential risks have not been demonstrated in vivo. Here, a humanized SCID-X1 mouse model was established, and 86.67% ± 2.52% (n = 3) of mouse hematopoietic stem cell (HSC) pathogenic mutations were corrected, with no single-guide-RNA (sgRNA)-dependent off-target effects detected. Analysis of peripheral blood over 16 weeks post-transplantation in mice with different immunodeficiency backgrounds revealed efficient immune cell generation following transplantation of different amounts of modified HSCs. Therefore, a large-scale infusion of gene-corrected HSCs within a safe range can achieve rapid, stable, and durable immune cell regeneration. Tissue-section staining further demonstrated the restoration of immune organ tissue structures, with no tumor formation in multiple organs. Collectively, these data suggest that base-edited HSCs are a potential therapeutic approach for SCID-X1 and that a threshold infusion dose of gene-corrected cells is required for immune cell regeneration. This study lays a theoretical foundation for the clinical application of base-edited HSCs in treating SCID-X1.

Visual authenticating hazardous adulterant phenolphthalein in slimming foods: Target-mimicking hapten epitope improved immunoassay.

Screening for the hazardous adulterant phenolphthalein (PTH) in slimming foods is necessary. Herein, the linkage of the PTH target epitope with various spacer arms was proposed for hapten design, aiming to produce highly sensitive and specific antibodies targeting PTH. To understand the influence of spacer arms on epitope, comprehensive evaluations were conducted using computer-aided chemistry and animal immunization. The resulting antibody exhibited maximal half-inhibitory concentration (IC50) of 0.25 ng/mL. Then, a lateral flow immunoassay (LFIA) was established with detection capability for screening (CCß) of less than 140, 240, and 25 ng/g for PTH in tea, instant coffee, and oral liquid, respectively. Furthermore, blind sample results agreed well with LFIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Therefore, this work not only provides a robust tool for detecting PTH adulteration but also suggests that the careful pairing of spacer arms with hapten epitope is a key factor in advancing rational hapten design.

Substrate types and applications of MXene for surface-enhanced Raman spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) has been widely used in the analysis of analytes because of its unique fingerprint characteristics, high sensitivity, and fast detection response. MXene is widely used in SERS studies among the various substrates due to its ultra-high chemical stability, excellent conductivity, hydrophilicity, and low fabrication cost. This mini-review summarizes MXene's research in the SERS field from two aspects. We reviewed MXene materials used as SERS substrates alone and combined with noble metal particles primarily. Subsequently, we outlined representative applications of MXene-based SERS in biomedicine, food safety, and environmental monitoring. Moreover, we discussed the technical bottleneck and the prospect of future development in this field.

Role of iron oxide in retarding the graphitization of de-oiled asphaltenes for amorphous carbon.

The solvent deasphalting (SDA) process is widely recognized as a significant technology in processing inferior oil. However, de-oiled asphaltene (DOA), which accounts for about 30% of feedstocks, is not well utilized in conventional processing methods to date. Considering its complicated structure and high heteroatom and metal contents, DOA is suitable for preparing amorphous carbon. Herein, we obtained amorphous carbon from inferior de-oiled asphaltene through direct carbonization of a mixture of DOA and Fe2O3 and revealed the mechanism of iron oxide in retarding graphitization to increase the disordered structure content. After the addition of Fe2O3, XRD results showed that the content of amorphous carbon increased from 25.57% to 59.48%, and a higher defect degree could also be observed in Raman spectra, thus resulting in better electrochemical performance in Na-ion half-cells. As a coke core, Fe2O3 could accelerate the polycondensation of asphaltene molecules; meanwhile, oxygen species derived from Fe2O3 could capture excess H free radicals in the initial pyrolysis stage, which inhibited the formation of planar polycyclic aromatic molecules and weakened π-π interactions. Moreover, O atoms could embed into the carbon skeleton by reacting with DOA at higher temperatures, which could further twist and break the intact carbon layer. Both of the factors enhanced the proportion of amorphous carbon. This work not only provides a new understanding of controlling the carbonization process, but it also promotes the development of the SDA process.

Electrospinning Silk-Fibroin-Based Fibrous Membranes with AgNPs for Antimicrobial Application.

Silk fibroin (SF) has excellent biocompatibility and is one of the most commonly used polymer materials. However, SF fibers have serious drawbacks as antibacterial materials due to their lack of stability and bacterial resistance. Therefore, it is of paramount significance to enhance the stability and bolster the bacterial resistance of SF fibers. In this study, SF fibers were fabricated and loaded with Ag nanoparticles (AgNPs) to improve the antimicrobial properties of the fibers. The impact of reduction conditions on the size of AgNPs was also investigated. In an antibacterial test, the fibers that were prepared exhibited over 98% bacterial resistance against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Therefore, as an efficient antibacterial material, these fibers are expected to become a candidate material in medical and textile fields. This study offers a novel approach for the utilization of SF fibers in the realm of antibacterial applications.