Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Rate-Pressure Product is a Novel Predictor for Short- and Long-Term Mortality in Patients with Acute Coronary Syndrome Undergoing Primary PCI/Immediate Invasive Strategy.

Background: Rate-pressure product (RPP) calculated by multiplying heart rate by systolic blood pressure, is a convenient indicator closely associated with cardiac work or myocardial oxygen consumption. It has been reported to relate strongly to important indices of cardiovascular risk in patients with myocardial ischemia. However, its relationship with short- and long-term mortality in patients with acute coronary syndrome (ACS) undergoing primary PCI/immediate invasive strategy has not been defined. Methods: This study analyzed 1301 consecutive ACS patients who had undergone primary PCI, between January 2018 and September 2021. Patients with systolic BP < 90 mmHg were excluded to avoid the confounding effect of cardiogenic shock. RPP values were collected on admission and were divided into four groups: RPP ≤ 7.4, 7.4 ≤ 8.8, 8.8 <8.8 < RPP8, and RPP > 10.8. Clinical endpoints were in-hospital cardiac and long-term all-cause mortality. The predictive performance was assessed by C-statistic, multivariate analysis and survival analysis. Results: Multivariate analysis showed that these in the highest vs lowest category of RPP (>10.8 vs ≤7.4) had OR of 4.33 (95% CI=1.10 -17.01; P = 0.036) in in-hospital cardiac mortality and 3.15 (95% CI=1.24 -8.00; P = 0.016) in long-term all-cause mortality. In C-statistic analyses, RPP was a strong predictor in ACS, STEMI or UA/NSTEMI group for in-hospital cardiac mortality (AUC = 0.746, 95% CI = 0.722-0.770, p < 0.001) and long-term all-cause mortality (AUC = 0.701, 95% CI = 0.675-0.725, p < 0.001). The Kaplan-Meier event rate for long-term survival of RPP > 10.8 was significantly lower than that of RPP ≤ 10.8. Conclusion: RPP showed a positive association with in-hospital cardiac or long-term all-cause mortality in ACS patients undergoing primary PCI/immediate invasive strategy, and RPP > 10.8 can be as an independent predictor.

Construction of an Enzymatically Controlled DNA Nanomachine for One-Step Imaging of Telomerase in Living Cells.

Telomerase is a basic reverse transcriptase that maintains the telomere length in cells, and accurate and specific sensing of telomerase in living cells is critical for medical diagnostics and disease therapeutics. Herein, we demonstrate for the first time the construction of an enzymatically controlled DNA nanomachine with endogenous apurinic/apyrimidinic endonuclease 1 (APE1) as a driving force for one-step imaging of telomerase in living cells. The DNA nanomachine is designed by rational engineering of substrate probes and reporter probes embedded with an enzyme-activatable site (i.e., AP site) and their subsequent assembly on a gold nanoparticle (AuNP). Upon recognition and cleavage of the AP site in the substrate probe by APE1, the loop of the substrate probe unfolds, exposing telomeric primer (TP) with the 3'-OH end. Subsequently, the TP is elongated by telomerase at the 3'-OH end to generate a long telomeric product. The resultant telomeric product acts as a swing arm that can hybridize with a reporter probe to initiate the APE1-powered walking reaction, ultimately generating a significantly enhanced fluorescence signal. Notably, endogenous APE1 is used as the driving force of the DNA nanomachine, avoiding the introduction of exogenous auxiliary cofactors into the cellular microenvironment. Owing to the high kinetics and high amplification efficiency of the APE1-powered DNA nanomachine, this strategy enables one-step sensitive sensing of telomerase in vitro and in vivo. It can successfully discriminate telomerase activity between cancer cells and normal cells, screen telomerase inhibitors, and monitor the variations of telomerase activity in living cells, offering a prospective platform for molecular diagnostics and drug discovery.

Accelerometer-measured sedentary volume and bouts during the segmented school day among Chinese school students.

Background: This study examined sedentary volume and bouts of Chinese primary and middle school students during different segments of a school day and determined whether gender and school level are associated with their sedentary volume and bouts. Methods: A total of 472 students participated in this study. Accelerometers were used to measure the sedentary volume and sedentary bouts of different durations (i.e., 1-4 min, 5-9 min and ≥10 min) during all segments. Results: The participants spent the majority of their time in sitting (61.7%) and sitting bouts of ≥10 min (37.3%). They spent higher percentages of time in sitting during regular classes (76.7%) and out-of-school time (54.5%), and lower during physical education (PE) classes (32.2%), lunch break (35.4%) and recess (38.0%). The highest proportions of time were in sedentary bouts of ≥10 min during regular classes (50.2%), out-of-school time (28.0%) and lunch break (18.8%), while the greatest percentages occurred in sitting bouts of 1-4 min during PE class (16.4%) and recess (18.6%). Girls and middle school students had higher percentages of sedentary volume than boys and primary school students during most segments. They spent greater proportions of time in sitting bouts of ≥10 min during regular classes, lunch break, and out-of-school time, and higher proportions in sedentary bouts of 1-4 min than boys and primary students during PE classes. Conclusion: Regular class and out-of-school time were identified as key segments for reducing sedentary volume and breaking up prolonged sitting. Interventions on interrupting prolonged sitting during lunch break should also be explored. Girls and middle school students should receive more attention in future interventions.

Life and disease status of patients with Parkinson's disease during and after zero-COVID in China: an online survey.

BACKGROUND: Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. METHODS: This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. RESULTS: A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%). CONCLUSIONS: The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.

Pirfenidone alleviates chronic pancreatitis via suppressing the activation of pancreatic stellate cells and the M1 polarization of macrophages.

In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.

Pharmacological and mechanistic aspects of quercetin in osteoporosis.

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient's life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/ß-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis.

BACKGROUND: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance. METHODS AND RESULTS: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE-/-) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE-/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis. CONCLUSIONS: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases.

Silver/Antimony-Base Multifunctional Double Perovskite with H/F Substitution Enhance Properties.

Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.

Silver-Coordinated Watson-Crick Pairing-Driven Three-Dimensional DNA Walker for Locus-Specific Detection of Genomic N6-Methyladenine and N4-Methylcytosine at the Single-Molecule Level.

N6-Methyladenine (6mdA) and N4-methylcytosine (4mdC) are the two most dominant DNA modifications in both prokaryotes and eukaryotes, but standard hybridization-based techniques cannot be applied for the 6mdA/4mdC assay. Herein, we demonstrate the silver-coordinated Watson-Crick pairing-driven three-dimensional (3D) DNA walker for locus-specific detection of genomic 6mdA/4mdC at the single-molecule level. 6mdA-DNA and 4mdC-DNA can selectively hybridize with the binding probes (BP1 and BP2) to form 6mdA-DNA-BP1 and 4mdC-DNA-BP2 duplexes. The 6mdA-C/4mdC-A mismatches cannot be stabilized by AgI, and thus, 18-nt BP1/BP2 cannot be extended by the catalysis of KF exonuclease. Through toehold-mediated strand displacement (TMSD), the signal probe (SP1/SP2) functionalized on the gold nanoparticles (AuNPs) can competitively bind to BP1/BP2 in 6mdA-DNA-BP1/4mdC-DNA-BP2 duplex to obtain SP1-18-nt BP1 and SP2-18-nt BP2 duplexes. The resulting DNA duplexes can act as the substrates of lambda exonuclease, leading to the cleavage of SP1/SP2 and the release of Cy3/Cy5 and 18-nt BP1/BP2. The released 18-nt BP1/BP2 can subsequently serve as the walker DNA, moving along the surface of the AuNP to activate dynamic 3D DNA walking and releasing abundant Cy3/Cy5. The released Cy3/Cy5 can be quantified by single-molecule imaging. This nanosensor exhibits high sensitivity with a limit of detection (LOD) of 9.80 × 10-15 M for 6mdA-DNA and 9.97 × 10-15 M for 4mdC-DNA. It can discriminate 6mdA-/4mdC-DNA from unmodified genomic DNAs, distinguish 0.01% 6mdA-/4mdC-DNA from excess unmethylated DNAs, and quantify 6mdA-/4mdC-DNA at specific sites in genomic DNAs of liver cancer cells and Escherichia coli plasmid cloning vector, providing a new platform for locus-specific analysis of 6mdA/4mdC in genomic DNAs.

Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration.

Amuc_1100 is a membrane protein from Akkermansia muciniphila, which has been found to play a role in host immunological homeostasis in the gastrointestinal tract by activating TLR2 and TLR4. In this study we investigated the effects and underlying mechanisms of Amuc_1100 on acute pancreatitis (AP) induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). The mice were treated with the protein Amuc_1100 (3 µg, i.g.) for 20 days before caerulein injection. Cecal contents of the mice were collected for 16S rRNA sequencing. We found that pretreatment with Amuc_1100 significantly alleviated AP-associated pancreatic injury, reduced serum amylase and lipase. Amuc_1100 pretreatment significantly inhibited the expression of proinflammatory cytokines (TNF-α, IL-1ß, IFN-γ and IL-6) in spleen and pancreas through inhibiting NF-κB signaling pathway. Moreover, Amuc_1100 pretreatment significantly decreased the inflammatory infiltration, accompanied by the reduction of Ly6C+ macrophages and neutrophils in the spleen of AP mice. Gut microbiome analysis showed that the abundance of Bacteroidetes, Proteobacteria, Desulfobacterota and Campilobacterota was decreased, while the proportion of Firmicutes and Actinobacteriota was increased in AP mice pretreated with Amuc_1100. We further demonstrated that Amuc_1100 pretreatment restored the enrichment of tryptophan metabolism, which was mediated by intestinal flora. These results provide new evidence that Amuc_1100 lessens the severity of AP through its anti-inflammatory properties with a reduction of macrophages and neutrophil infiltration, as well as its regulation of the composition of intestinal flora and tryptophan metabolism.

A phase I dose-finding trial of hyperthermic intraperitoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian cancer.

OBJECTIVE: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m²) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. METHODS: In this phase I trial, a time-to-event Bayesian optimal interval design was used. Docetaxel was given at a starting dose of 60 mg/m² and was increased in 5 mg/m² increments until the MTD was determined or the maximum dose level of 75 mg/m² was reached. The dose-limiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. RESULTS: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m², no DLT was reported. DLTs were observed in one patient who received 70 mg/m² docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m² docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. CONCLUSION: Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m²), can be used safely at intraperitoneal doses of 75 mg/m² in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05410483.

Investigating the Structure-property Relationships of Two Cd-based Hybrid Multifunctional Compounds with High Tc, Bright Fluorescence and Wide Band-gap.

Organic-inorganic hybrid multifunctional materials have shown significant application in lighting and sensor fields, owing to their prominent performance and diversity structures. Herein, we synthesized two multifunctional compounds: (propyl-quinuclidone)2 CdBr4 (1) and (F-butyl-quinuclidone)2 CdBr4 (2). By introducing light-emitting organic cation with flexible long chain, 1 and 2 exhibit excellent transition properties and bright blue-white fluorescence. Then, combine fluorescence lifetime and first-principal calculation, providing evidence for the electron transfer emission. Subsequently, investigated the impact of substituent carbon chain length (methyl to butyl), structural rigidity (C-C to C-F) and halide framework (Cl to I) on the fluorescence properties. Results indicate that Cd⋅⋅⋅Cd distance and structural rigidity play an important role in fluorescence. Overall, our research provides valuable insight and example for chemical modifications enhance compound performance.

Retracted: Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Mei Mei Guan, Qun Xian Rao, Miao Ling Huang, Li Juan Wang, Shao Dan Lin, Qing Chen, Chang Hao Liu. Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines. Med Sci Monit, 2019; 25: 8131-8141. DOI: 10.12659/MSM.916292.

Association of HLA-A, B, and C alleles and cancer susceptibility in 179 solid malignancies.

BACKGROUND: The major histocompatibility complex (MHC) genes are known to be capable of influencing the susceptibility of many cancers. All mammalian cells, including cancer cells, express MHC class I molecules consisting of human leukocyte antigens (HLA) A, B, and C. The tumor susceptibility of HLA-A, B, and C alleles has not been studied extensively in solid tumors. METHODS: HLA-A, B, and C genotypes of 179 solid tumors were collected from Caris Comprehensive Tumor Profiling reports, including 45 GU, 44 GI, 28 pancreaticobiliary, 21 thoracic, 15 breast, 13 Gyn, among others. The tumors were mainly from Caucasians (82%). The HLA allele frequencies in the tumors were compared to those of respective ethnic populations in the US National Marrow Donor Program (NMDP) database. Fisher's exact tests were performed, adjusted P values were calculated using Benjamini-Hochberg's method for false discovery rate (FDR), and Prevalence ratios (PRs) were calculated to quantify associations. RESULTS: Twenty-one alleles were not listed in the NMDP. Among them, A*11:303 alone was present in 11 carcinomas, and B*08:222 was seen in 4 tumors. Among the alleles listed in the NMDP, C*08:02, B*14:02, A*03:02, and B*44:06 were significantly associated with tumors in Caucasian Americans (PR: 2.50-170), while B*44:02 appeared protective (PR: 0.36). Alleles with less significant associations were listed. CONCLUSIONS: From the HLA-A, B, and C data of the 179 tumors, we identified several susceptible alleles and one protective allele. Of interest, 21 alleles were not listed in the NMDP. The limited cases prevented our analysis from identifying cancer-susceptible alleles in other races.

Creation of Environmentally Friendly Super "Dinitrotoluene Scavenger" Plants.

Pervasive environmental contamination due to the uncontrolled dispersal of 2,4-dinitrotoluene (2,4-DNT) represents a substantial global health risk, demanding urgent intervention for the removal of this detrimental compound from affected sites and the promotion of ecological restoration. Conventional methodologies, however, are energy-intensive, susceptible to secondary pollution, and may inadvertently increase carbon emissions. In this study, a 2,4-DNT degradation module is designed, assembled, and validated in rice plants. Consequently, the modified rice plants acquire the ability to counteract the phytotoxicity of 2,4-DNT. The most significant finding of this study is that these modified rice plants can completely degrade 2,4-DNT into innocuous substances and subsequently introduce them into the tricarboxylic acid cycle. Further, research reveals that the modified rice plants enable the rapid phytoremediation of 2,4-DNT-contaminated soil. This innovative, eco-friendly phytoremediation approach for dinitrotoluene-contaminated soil and water demonstrates significant potential across diverse regions, substantially contributing to carbon neutrality and sustainable development objectives by repurposing carbon and energy from organic contaminants.

Progress in quantum dot-based biosensors for microRNA assay: A review.

MicroRNAs (miRNAs) are responsible for post-transcriptional gene regulation, and may function as valuable biomarkers for diseases diagnosis. Accurate and sensitive analysis of miRNAs is in great demand. Quantum dots (QDs) are semiconductor nanomaterials with superior optoelectronic features, such as high quantum yield and brightness, broad absorption and narrow emission, long fluorescence lifetime, and good photostability. Herein, we give a comprehensive review about QD-based biosensors for miRNA assay. Different QD-based biosensors for miRNA assay are classified by the signal types including fluorescent, electrochemical, electrochemiluminescent, and photoelectrochemical outputs. We highlight the features, principles, and performances of the emerging miRNA biosensors, and emphasize the challenges and perspectives in this field.

Colorimetric and ratiometric supramolecular AIE fluorescent probe for the on-site monitoring of fipronil.

The overuse of fipronil (FPN, a broad-spectrum insecticide) in agriculture has brought great concerns for environmental pollution and food safety. The development of a rapid, reliable, and portable analytical method for the on-site monitoring of FPN is therefore of great significance but is full of challenge. Herein, a novel supramolecular probe using human serum albumin (HSA) as the host and an aggregation-induced emission-active fluorescence probe LIQ-TPA-TZ as the guest was developed for the colorimetric and ratiometric detection of FPN, displaying fast response (30 s), high sensitivity (LOD ∼ 0.05 µM), and good selectivity and anti-interference performance. Moreover, portable paper-based test strips could be facilely obtained and utilized for the determination of FPN, showing colorimetric changes from yellow to orange. This supramolecular probe also demonstrated great potential in real applications for choosing the best cleaning method to reduce the residue rate of FPN on apples. This study provides a versatile tool for the fast and real-time analysis of FPN, which greatly benefits the on-site determination of pesticides with the use of simple testing apparatus.

Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is the major complication of liver surgery and liver transplantation, that may increase the postoperative morbidity, mortality, tumor progression, and metastasis. The underlying mechanisms have been extensively investigated in recent years. Among these, oxidative stress, inflammatory responses, immunoreactions, and cell death are the most studied. Non-coding RNAs (ncRNAs) are defined as the RNAs that do not encode proteins, but can regulate gene expressions. In recent years, ncRNAs have emerged as research hotspots for various diseases. During the progression of HIRI, ncRNAs are differentially expressed, while these dysregulations of ncRNAs, in turn, have been verified to be related to the above pathological processes involved in HIRI. ncRNAs mainly contain microRNAs, long ncRNAs, and circular RNAs, some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity, and as therapeutic targets to attenuate HIRI. Here, we briefly summarize the common pathophysiology of HIRI, describe the current knowledge of ncRNAs involved in HIRI in animal and human studies, and discuss the potential of ncRNA-targeted therapeutic strategies. Given the scarcity of clinical trials, there is still a long way to go from pre-clinical to clinical application, and further studies are needed to uncover their potential as therapeutic targets.

Nintedanib Alleviates Chronic Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells via the JAK/STAT3 and ERK1/2 Pathways.

BACKGROUND: Nintedanib (Ninte) has been approved for the treatment of pulmonary fibrosis, and whether it can ameliorate chronic pancreatitis (CP) is unknown. AIMS: This study was conducted to investigate the effect and molecular mechanism of Ninte on pancreatic fibrosis and inflammation in vivo and in vitro. METHODS: The caerulein-induced CP model of murine was applied, and Ninte was orally administered. Pathological changes in pancreas were evaluated using hematoxylin & eosin, Sirius Red, Masson's trichrome, and anti-Ki-67 staining. For in vitro studies, the effects of Ninte on cell viability, apoptosis, and migration of pancreatic stellate cells (PSCs) were determined by CCK-8, flow cytometry, and wound healing assays, respectively. The potential molecular mechanisms of the effects of Ninte on PSCs were analyzed by RNA-Seq and verified at the gene expression and protein activity levels by qRT-PCR and Western Blot. RESULTS: Ninte significantly alleviated the weight loss in mice with caerulein-induced CP and simultaneously attenuated the pancreatic damage, as evidenced by reduced acinar atrophy, collagen deposition, infiltration of inflammatory cells, and inhibited cell proliferation/regeneration. Besides, Ninte markedly suppressed the transcription of fibrogenic and proinflammatory genes in pancreatic tissues. Further in vitro studies showed that Ninte significantly inhibited the transcription and protein expression of genes corresponding to fibrogenesis and proliferation in PSCs. The results of RNA-Seq analysis and subsequent verification assays indicated that Ninte inhibited the activation and proliferation of PSCs via the JAK/STAT3 and ERK1/2 pathways. CONCLUSIONS: These findings indicate that Ninte may be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP.