HCR-Assisted RTF-EXPAR-Based Lateral Flow Analysis for Sensitive Detection of H1N1 Influenza Virus.

The H1N1 influenza virus is a significant pathogen responsible for seasonal influenza, and its frequent outbreaks pose substantial challenges to global public health. The present study successfully developed a lateral flow analysis platform that integrates reverse transcription-free exponential amplification reaction (RTF-EXPAR) and hybridization chain reaction (HCR) processes with functionalized quantum dots for the direct detection of H1N1 influenza virus RNA, eliminating the need for reverse transcription. The fluorescence signal on the band recorded with a smartphone can be utilized for the quantitative determination of the target. Interestingly, the dual signal amplification strategy exhibits high sensitivity with a remarkably low detection limit of 10 aM. Moreover, this platform exhibits excellent flexibility and universality, where the various pathogens can be determined by replacing the specific nucleic acid fragments in RTF-EXPAR. The aforementioned advantages reveal its huge potential in the early diagnosis of H1N1 influenza virus infection and developing point-of-care testing (POCT) equipment for nucleic acid analysis.

The effects of noise exposure on hippocampal cognition in C57BL/6 mice via transcriptomics.

BACKGROUND: Noise is an important environmental stressor in the industrialized world and has received increasing attention in recent years. Although epidemiological research has extensively demonstrated the relationship between noise and cognitive impairment, the specific molecular mechanisms and targets remain to be fully explored and understood. METHODS: To address this issue, 5-month-old C57BL/6 mice were divided into two groups, with one group exposed to white noise at 98 dB. The effects of noise on cognition in mice were investigated through molecular biology and behavioral experiments. Subsequently, transcriptomic sequencing of the hippocampus in both groups of mice was performed and enrichment analysis of differentially expressed genes (DEGs) was conducted using KEGG and GO databases. Furthermore, LASSO analysis was used to further narrow down the relevant DEGs, followed by enrichment analysis of these genes using KEGG and GO databases. The DEGs were further validated by rt-qPCR. RESULTS: Following noise exposure, the hippocampus levels of inflammation-related factors increased, the phosphorylation of Tau protein increased, the postsynaptic density protein decreased, the number of Nissl bodies decreased, and cell shrinkage in the hippocampus increased. Moreover, the behavioral experiments manifest characteristics indicative of a decline in cognitive.A total of 472 DEGs were identified through transcriptomic analysis, and seven relevant genes were screened by the LASSO algorithm, which were further validated by PCR to confirm their consistency with the omics results. CONCLUSION: In conclusion, noise exposure affects cognitive function in mice through multiple pathways, and the omics results provide new evidence for the cognitive impairment induced by noise exposure.

Modeling denitrification nitrogen losses in China's rice fields based on multiscale field-experiment constraints.

Denitrification plays a critical role in soil nitrogen (N) cycling, affecting N availability in agroecosystems. However, the challenges in direct measurement of denitrification products (NO, N2 O, and N2 ) hinder our understanding of denitrification N losses patterns across the spatial scale. To address this gap, we constructed a data-model fusion method to map the county-scale denitrification N losses from China's rice fields over the past decade. The estimated denitrification N losses as a percentage of N application from 2009 to 2018 were 11.8 ± 4.0% for single rice, 12.4 ± 3.7% for early rice, and 11.6 ± 3.1% for late rice. The model results showed that the spatial heterogeneity of denitrification N losses is primarily driven by edaphic and climatic factors rather than by management practices. In particular, diffusion and production rates emerged as key contributors to the variation of denitrification N losses. These findings humanize a 38.9 ± 4.8 kg N ha-1 N loss by denitrification and challenge the common hypothesis that substrate availability drives the pattern of N losses by denitrification in rice fields.

Novel Chemical Routes for Carbon Dioxide and Methane Production from Lignin Photodegradation: The Role of Environmental Free Radicals.

Sunlight irradiation significantly mediates plant litter's carbon dynamics and volatile carbon release in semi-arid and arid ecosystems. In this process, carbon loss is controlled by lignin, but the mechanisms of production of CO2 and CH4 during lignin photolysis are ambiguous. In this study, the photomineralization of plant litter and the lignocellulosic component collectively indicate that lignin is a major source of CO2 and CH4 emissions. Characterization and free radical analysis reveal that the production of CO2 is due to the oxidation and ring-opening reaction of the coniferyl alcohol unit, with the subsequent decarboxylation of carboxylic acid as an oxidation product. This reaction involves o-quinone formation by the reactions between O2, superoxide radical (O2·-), and persistent free radicals (PFRs)-bearing lignin. Of this, O2·- contributes to 43.2% of the photogenerated CO2, as a new pathway, derived from the electron transfer from PFRs to O2. Interestingly, photoinduced demethylation of the dimethoxybenzene-type compounds as the photolysis products of lignin results in a never-before-reported CH4 formation chemical route independent of that of O2. This mechanistic insight into the role of lignin in volatile carbon production from the irradiative plant litter will contribute to a deeper understanding of carbon balance in water-limited ecosystems.

Seasonal and Spatial Fluctuations of Reactive Oxygen Species in Riparian Soils and Their Contributions on Organic Carbon Mineralization.

Reactive oxygen species (ROS) are ubiquitous in the natural environment and play a pivotal role in biogeochemical processes. However, the spatiotemporal distribution and production mechanisms of ROS in riparian soil remain unknown. Herein, we performed uninterrupted monitoring to investigate the variation of ROS at different soil sites of the Weihe River riparian zone throughout the year. Fluorescence imaging and quantitative analysis clearly showed the production and spatiotemporal variation of ROS in riparian soils. The concentration of superoxide (O2•-) was 300% higher in summer and autumn compared to that in other seasons, while the highest concentrations of 539.7 and 20.12 µmol kg-1 were observed in winter for hydrogen peroxide (H2O2) and hydroxyl radicals (•OH), respectively. Spatially, ROS production in riparian soils gradually decreased along with the stream. The results of the structural equation and random forest model indicated that meteorological conditions and soil physicochemical properties were primary drivers mediating the seasonal and spatial variations in ROS production, respectively. The generated •OH significantly induced the abiotic mineralization of organic carbon, contributing to 17.5-26.4% of CO2 efflux. The obtained information highlighted riparian zones as pervasive yet previously underestimated hotspots for ROS production, which may have non-negligible implications for carbon turnover and other elemental cycles in riparian soils.

Functional analysis of a rice 12-oxo-phytodienoic acid reductase gene (OsOPR1) involved in Cd stress tolerance.

BACKGROUND: The accumulation of cadmium (Cd) in plants may compromise the growth and development of plants, thereby endangering human health through the food chain. Understanding how plants respond to Cd is important for breeding low-Cd rice cultivars. METHODS: In this study, the functions of 12-oxo-phytodienoic acid reductase 1 (OsOPR1) were predicted through bioinformatics analysis. The expression levels of OsOPR1 under Cd stress were analyzed by using qRT-PCR. Then, the role that OsOPR1 gene plays in Cd tolerance was studied in Cd-sensitive yeast strain (ycf1), and the Cd concentration of transgenic yeast was analyzed using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Bioinformatics analysis revealed that OsOPR1 was a protein with an Old yellow enzyme-like FMN (OYE_like_FMN) domain, and the cis-acting elements which regulate hormone synthesis or responding abiotic stress were abundant in the promoter region, which suggested that OsOPR1 may exhibit multifaceted biological functions. The expression pattern analysis showed that the expression levels of OsOPR1 were induced by Cd stress both in roots and roots of rice plants. However, the induced expression of OsOPR1 by Cd was more significant in the roots compared to that in roots. In addition, the overexpression of OsOPR1 improved the Cd tolerance of yeast cells by affecting the expression of antioxidant enzyme related genes and reducing Cd content in yeast cells. CONCLUSION: Overall, these results suggested that OsOPR1 is a Cd-responsive gene and may has a potential for breeding low-Cd or Cd-tolerant rice cultivars and for phytoremediation of Cd-contaminated in farmland.

Effect of long-acting PEGylated growth hormone for catch-up growth in children with idiopathic short stature: a 2-year real-world retrospective cohort study.

Several evidence gaps exist regarding the use of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS), particularly studies conducted in real-world settings, with long-term follow-up, involving varied dosing regimens, and in comparison with daily rhGH. The study aimed to evaluate the effectiveness, safety, and adherence of once-weekly PEG-rhGH for catch-up growth in children with prepubertal ISS compared to daily rhGH. A real-world retrospective cohort study was conducted in prepubertal children with ISS in China. Children who voluntarily received once-weekly PEG-rhGH or daily rhGH were included and were followed up for 2 years. Ninety-five children were included, 47 received PEG-rhGH 0.2-0.3 mg/kg weekly and 48 received daily rhGH. Outcome measures included effectiveness in catch-up growth, adverse events, and treatment adherence. Height velocity increased significantly in both groups during rhGH therapy. In children who received PEG-rhGH treatment, height velocity was 10.59 ± 1.37 cm/year and 8.75 ± 0.86 cm/year in the first and second year, respectively, which were significantly more than those who received daily rhGH (9.80 ± 1.05 cm/year, P = 0.002, and 8.03 ± 0.89 cm/year, P < 0.001). The height standard deviation score improved at the end of the second year for all children (P < 0.001). However, children who received PEG-rhGH showed more excellent improvement than those with daily rhGH (1.65 ± 0.38 vs. 1.50 ± 0.36, P = 0.001). In children who received PEG-rhGH, lower missed doses were observed than those with daily rhGH (0.75 ± 1.06 vs. 4.4 ± 2.0, P < 0.001). No serious adverse events were observed. CONCLUSION: PEG-rhGH demonstrated superior effectiveness and adherence compared to daily rhGH in the treatment of children with ISS. The safety profiles were similar between the two treatments. WHAT IS KNOWN: • Recombinant human growth hormone (rhGH) has been used to increase adult height in children with idiopathic short stature (ISS), and its safety profile is comparable to other indications for growth hormone treatment. • The use of long-acting rhGH in children with ISS is still an area of uncertainty. WHAT IS NEW: • This 2-year real-world study provides new evidence that PEGylated rhGH (PEG-rhGH) is more effective than daily rhGH in promoting catch-up growth in children with ISS. • PEG-rhGH also demonstrated superior treatment adherence compared to daily rhGH in children with ISS. • The safety profiles of PEG-rhGH and daily rhGH were found to be similar.

Crop bioengineering via gene editing: reshaping the future of agriculture.

Genome-editing technologies have revolutionized research in plant biology, with major implications for agriculture and worldwide food security, particularly in the face of challenges such as climate change and increasing human populations. Among these technologies, clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR-associated protein [Cas] systems are now widely used for editing crop plant genomes. In this review, we provide an overview of CRISPR-Cas technology and its most significant applications for improving crop sustainability. We also review current and potential technological advances that will aid in the future breeding of crops to enhance food security worldwide. Finally, we discuss the obstacles and challenges that must be overcome to realize the maximum potential of genome-editing technologies for future crop and food production.

UHPLC-QTOF-MS-Based Targeted Metabolomics Provides Novel Insights into the Accumulative Mechanism of Soil Types on the Bioactive Components of Salvia miltiorrhiza.

The root of Salvia miltiorrhiza Bunge (SMB) has been widely used to treat cardiovascular diseases. However, the contents of secondary metabolites in the roots from different production areas are significantly different, and the impact of soil factors on this accumulation remains unclear. Therefore, this study aimed to elucidate the regularity of variation between the active components and soil factors through targeted metabolomics and chemical dosimetry. Soils were collected from five different cities (A, B, C, D, and E) and transplanted into the study area. The results showed that there were significant differences in the soil fertility characteristics and heavy metal pollution levels in different soils. Ten water- and twelve lipid-soluble metabolites were identified in SMBs grown in all soil types. SMBs from D cities exhibited the highest total tanshinone content (p < 0.05). The salvianolic acid B content in SMBs from E cities was the highest (p < 0.05). Interestingly, correlation analysis revealed a significant negative correlation between the accumulation of lipid-soluble and water-soluble metabolites. Double-matrix correlation analysis demonstrated that available potassium (AK) was significantly negatively correlated with salvianolic acid B (r = -0.80, p = 0.0004) and positively correlated with tanshinone IIA (r = 0.66, p = 0.008). Conversely, cadmium (Cd) and cuprum (Cu) were significantly positively and negatively correlated with salvianolic acid B (r = 0.96, p < 0.0001 and r = 0.72, p = 0.0024) and tanshinone IIA (r = 0.40, p = 0.14 and r = 0.73, p = 0.0018), respectively. Mantel's test indicated that AK (r > 0.52, p < 0.001), Cu (r > 0.60, p < 0.005), and Cd (r > 0.31, p < 0.05) were the primary drivers of the differences in the active components of SMBs. These findings provide a theoretical framework for modulating targeted metabolites of SMB through soil factors, with significant implications for the cultivation and quality control of medicinal plants.

Achieving Highly Efficient Photocatalytic Hydrogen Evolution through the Construction of g-C3N4@PdS@Pt Nanocomposites.

Selective supported catalysts have emerged as a promising approach to enhance carrier separation, particularly in the realm of photocatalytic hydrogen production. Herein, a pioneering exploration involves the loading of PdS and Pt catalyst onto g-C3N4 nanosheets to construct g-C3N4@PdS@Pt nanocomposites. The photocatalytic activity of nanocomposites was evaluated under visible light and full spectrum irradiation. The results show that g-C3N4@PdS@Pt nanocomposites exhibit excellent properties. Under visible light irradiation, these nanocomposites exhibit a remarkable production rate of 1289 µmol·g-1·h-1, marking a staggering 60-fold increase compared to g-C3N4@Pt (20.9 µmol·g-1·h-1). Furthermore, when subjected to full spectrum irradiation, the hydrogen production efficiency of g-C3N4@PdS@Pt-3 nanocomposites reaches an impressive 11,438 µmol·g-1·h-1, representing an eightfold enhancement compared to g-C3N4@Pt (1452 µmol·g-1·h-1) under identical conditions. Detailed investigations into the microstructure and optical properties of g-C3N4@PdS catalysts were conducted, shedding light on the mechanisms governing photocatalytic hydrogen production. This study offers valuable insights into the potential of these nanocomposites and their pivotal role in advancing photocatalysis.

Bioinformatic and functional analysis of OsDHN2 under cadmium stress.

As a toxic heavy metal, cadmium (Cd) is one of the principal pollutants influencing rice productivity and food security. Despite several studies, the underlying mechanism of Cd response in plants remains largely unclear. Dehydrins are part of the late embryogenesis abundant (LEA) family which protect plants against abiotic stresses. In this study, a Cd-responsive LEA gene, OsDHN2, was functionally characterized. The chromosome localization results indicated that OsDHN2 was located on chromosome 2 of rice. Meanwhile, cis-acting elements, such as MBS (MYB binding site involved in drought-inducibility), ARE (anaerobic induction), and ABRE (abscisic acid), were present in the OsDHN2 promoter region. Expression pattern analysis also showed that OsDHN2 expression was induced in both roots and shoots under Cd stress. Overexpression of OsDHN2 improved Cd tolerance and reduced Cd concentration in yeast. Moreover, increased expression levels of SOD1, CTA1, GSH1, or CTT1 were found in transgenic yeast under Cd stress, suggesting the increased antioxidant enzymatic activities. These results suggested that OsDHN2 is a Cd-responsive gene that has the potential to improve resistance to Cd in rice.

PNA-Pdx: Versatile Peptide Nucleic Acid-Based Detection of Nucleic Acids and SNPs.

Monitoring diseases caused by pathogens or by mutations in DNA sequences requires accurate, rapid, and sensitive tools to detect specific nucleic acid sequences. Here, we describe a new peptide nucleic acid (PNA)-based nucleic acid detection toolkit, termed PNA-powered diagnostics (PNA-Pdx). PNA-Pdx employs PNA probes that bind specifically to a target and are then detected in lateral flow assays. This can precisely detect a specific pathogen or genotype genomic sequence. PNA probes can also be designed to invade double-stranded DNAs (dsDNAs) to produce single-stranded DNAs for precise CRISPR-Cas12b-based detection of genomic SNPs without requiring the protospacer-adjacent motif (PAM), as Cas12b requires PAM sequences only for dsDNA targets. PNA-Pdx identified target nucleic acid sequences at concentrations as low as 2 copies/µL and precisely detected the SARS-CoV-2 genome in clinical samples in 40 min. Furthermore, the specific dsDNA invasion by the PNA coupled with CRISPR-Cas12b precisely detected genomic SNPs without PAM restriction. Overall, PNA-Pdx provides a novel toolkit for nucleic acid and SNP detection as well as highlights the benefits of engineering PNA probes for detecting nucleic acids.

Noise exposure increase apoptosis in the hippocampus of AD mice through the upregulation of CTSS.

In recent years, it has become an acknowledged fact that noise exposure can lead to cognitive impairments, and researchers have shown increasing interest in this area. However, the detrimental impact of noise exposure on Alzheimer's disease (AD) animal models might be considerably greater than on ordinary model mice, yet the mechanisms by which noise exposure affects the hippocampus in these models have been scarcely investigated. This study we used 4D Label-free proteomics to identify distinctive differentially expressed proteins in the hippocampus of AD model mice following noise exposure. Among these proteins, the presence of Cathepsin S(CTSS) cannot be disregarded. Utilizing experimental techniques such as Western blot, immunofluorescence, and rt-qPCR, we confirmed the expression of CTSS in the hippocampus of APP/PS1 mice after noise exposure. Additionally, we examined downstream molecules including P53,BCL-2, BAX, and CASPASE3 using KEGG pathway analysis. The results indicated an elevation in CTSS expression, a reduction in the anti-apoptotic gene BCL-2, and an increase in the expression of BAX and cleaved CASPASE3. Based on these findings, we hypothesize that noise exposure potentially heightens apoptosis within the hippocampus through upregulating CTSS expression, subsequently posing a threat to AD model animals.

PGC-1α affects cochlear pericytes migration in noise-exposed mice.

OBJECTIVE: The study aimed to observe the effects of noise exposure on the pericytes of the cochlear stria vascularis (SV) in mice and to investigate its molecular mechanism. METHOD: Male C57BL/6J mice aged 6-8 weeks were used as the subjects. Auditory Brainstem Response (ABR) was used to assess hearing loss. Hematoxylin and Eosin (HE) staining was conducted to observe morphological alterations in the SV. Immunofluorescence combined with transmission electron microscopy (TEM) was used to scrutinize changes in pericytes following acoustic injury. Western blotting (WB) was used to assess the expression variations of the migration-related protein Osteopontin (OPN). Evans Blue assay was performed to evaluate the permeability of the blood labyrinth barrier (BLB). 4-Hydroxynonenal (4-HNE) staining, in conjunction with measurements of Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Catalase (CAT) content, was used to ascertain whether oxidative stress injury occurred in the SV. WB, combined with immunofluorescence, was used to examine alterations in the expression of proliferator-activated receptor-gamma coactivator 1α (PGC-1α) in the SV and pericytes. RESULTS: Noise exposure resulted in permanent hearing loss in C57BL/6J mice, accompanied by SV swelling, migration of pericytes from their vascular attachments, BLB leakage, elevated oxidative stress levels in the SV, and reduced expression of PGC-1α on both the SV and migrating pericytes. CONCLUSION: Noise exposure may potentially increase oxidative stress levels in the SV, downregulate the expression levels of PGC-1α, promote pericytes migration, and subsequently lead to an elevation in BLB permeability.

Expression of OsHARBI1-1 enhances the tolerance of Arabidopsis thaliana to cadmium.

BACKGROUND: As one of the major food crops in the world, rice is vulnerable to cadmium (Cd) pollution. Understanding of the molecular mechanisms of Cd uptake, transport and detoxification in rice is essential for the breeding of low-Cd rice. However, the molecular mechanisms underlying the response of rice to Cd stress remains to be further clarified. RESULTS: In this study, a novel Cd-responsive gene OsHARBI1-1 was identified in the rice genome and its expression pattern and function were characterized. Bioinformatics analysis showed that the promoter region of OsHARBI1-1 had multiple cis-acting elements in response to phytohormones and stress, and the expression of OsHARBI1-1 was induced by phytohormones. OsHARBI1-1 protein was targeted to the nucleus. qRT-PCR analysis results showed that the expression of OsHARBI1-1 in the roots was repressed while the expression in the shoots was increased under Cd stress. Heterologous expression of OsHARBI1-1 in yeast conferred tolerance to Cd and reduced Cd content in the cells. Meanwhile, the expression of OsHARBI1-1 in Arabidopsis thaliana (A. thaliana) enhanced the tolerance of A. thaliana to Cd stress. In addition, compared with the wild type plants, the POD activity of transgenic plants was increased, while the SOD and CAT activities were decreased. Interestingly, the accumulation of Cd in the roots of A. thaliana expressing OsHARBI1-1 was significantly increased, whereas the Cd accumulation in the shoots was slightly decreased. Compared to the WT plants, the expression of genes related to Cd absorption and chelation was upregulated in transgenic A. thaliana under Cd stress, while the expression of genes responsible for the translocation of Cd from the roots to the shoots was downregulated. Moreover, the expression of phytohormone-related genes was significantly influenced by the expression of OsHARBI1-1 with and without Cd treatment. CONCLUSIONS: Findings of this study suggest that OsHARBI1-1 might play a role in the response of plants to Cd response by affecting antioxidant enzyme activities, Cd chelation, absorption and transport, and phytohormone homeostasis and signaling.

The potential of high-order features of routine blood test in predicting the prognosis of non-small cell lung cancer.

BACKGROUND: Numerous studies have demonstrated that the high-order features (HOFs) of blood test data can be used to predict the prognosis of patients with different types of cancer. Although the majority of blood HOFs can be divided into inflammatory or nutritional markers, there are still numerous that have not been classified correctly, with the same feature being named differently. It is an urgent need to reclassify the blood HOFs and comprehensively assess their potential for cancer prognosis. METHODS: Initially, a review of existing literature was conducted to identify the high-order features (HOFs) and classify them based on their calculation method. Subsequently, a cohort of patients diagnosed with non-small cell lung cancer (NSCLC) was established, and their clinical information prior to treatment was collected, including low-order features (LOFs) obtained from routine blood tests. The HOFs were then computed and their associations with clinical features were examined. Using the LOF and HOF data sets, a deep learning algorithm called DeepSurv was utilized to predict the prognostic risk values. The effectiveness of each data set's prediction was evaluated using the decision curve analysis (DCA). Finally, a prognostic model in the form of a nomogram was developed, and its accuracy was assessed using the calibration curve. RESULTS: From 1210 documents, over 160 blood HOFs were obtained, arranged into 110, and divided into three distinct categories: 76 proportional features, 6 composition features, and 28 scoring features. Correlation analysis did not reveal a strong association between blood features and clinical features; however, the risk value predicted by the DeepSurv LOF- and HOF-models is significantly linked to the stage. Results from DCA showed that the HOF model was superior to the LOF model in terms of prediction, and that the risk value predicted by the blood data model could be employed as a complementary factor to enhance the prognosis of patients. A nomograph was created with a C-index value of 0.74, which is capable of providing a reasonably accurate prediction of 1-year and 3-year overall survival for patients. CONCLUSIONS: This research initially explored the categorization and nomenclature of blood HOF, and proved its potential in lung cancer prognosis.

Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies.

BACKGROUND: Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids. METHODS: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose. INTERPRETATION: We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/).

Sulfur-Containing Persistent Free Radicals and Reactive Species on Photoaged Microplastics: Identification and the Formation Mechanism.

The elemental composition may affect the persistent free radical (PFR) and reactive species (RS) formation associated with photoaging microplastics; however, a relevant study is still lacking. This study systematically investigated the formation, evolution, and types of PFRs and RS on sulfur-containing microplastics (S-MPs) under simulated sunlight. Electron paramagnetic resonance detection and power saturation curve analysis isolated three different PFRs on each photoaging poly(phenylene sulfide) (PPS) and polysulfone (PSF). Combining the results of characterization and density functional theory calculation, these observed PFRs on the irradiated S-MPs were classified as oxygen-centered radicals with an adjacent S atom (namely, thio-oxygen radicals), oxygen-centered and sulfur-centered radicals, where the thio-oxygen radicals on PPS were benzenethiol-like radicals, and oxygen-centered radicals and sulfur-centered radicals on PSF that were identified as benzenesulfonic-like radicals and phenyl sulfonyl-like radicals, respectively. Moreover, potential precursor molecule fragments of PFRs on the photoaging S-MPs, including p-toluenesulfinic acid and benzenesulfonic acid, were detected by pyrolysis-gas chromatography/mass spectrometry and liquid chromatography-mass spectrometry. Interestingly, reactive sulfur species (SO3•-) was also observed on irradiated S-MPs in addition to reactive oxygen species, which was mainly derived from the reaction of •OH and sulfonyl radicals. These results have implications for assessing the potential risks of atmospheric S-MPs.

Multiple fluorescence polymer dots-based differential array sensors for highly efficient heavy metal ions detection.

Water pollution caused by harmful heavy metal ions (HMIs) can significantly impact aquatic ecosystems and pose a high risk to human health. In this work, equipped with ultra-high fluorescence brightness, efficient energy transfer, and environmentally friendly performance, polymer dots (Pdots) were employed to construct a pattern recognition fluorescent HMIs detection platform. A single-channel unary Pdots differential sensing array was first developed to identify multiple HMIs with 100% classification accuracy. Then an "all-in-one" multiple Förster resonance energy transfer (FRET) Pdots differential sensing platform was constructed to discriminate HMIs in the artificial polluted water samples and actual water samples, exhibiting high classification accuracy in distinguishing HMIs. The proposed strategy leverages the compounded cumulative differential variation of diverse sensing channels for analytes, which is anticipated to find extensive applications in other fields for detection purposes.

Cold stress causes liver damage by inducing ferroptosis through the p38 MAPK/Drp1 pathway.

Acute extreme cold exposure impairs human health and even causes hypothermia which threatens human life. Liver, as a hub in metabolism and thermogenesis, is vital for cold acclimatization. Although accumulating evidence has suggested that cold exposure can cause liver damage, the underlying mechanisms remain poorly understood. This study investigated the role and underlying mechanisms of ferroptosis in cold stress-induced liver damage. To evaluate the role of ferroptosis in cold stress-induced liver damage, rats were pretreated with ferroptosis inhibitor liproxstatin-1 (Lip-1) before exposed to -10 °C for 8 h. Core body temperature was recorded. The levels of ferroptosis-related indicators were examined with the corresponding assay kits or by western blotting. Hepatic pathological changes were analyzed by hematoxylin-eosin staining and ultrastructural observation. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess liver function. Rats were also pretreated with p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or Dynamin-related protein 1 (Drp1) inhibitor Mdivi-1 to determine the underlying mechanisms. We found that Lip-1 inhibited ferroptosis, attenuated hepatic pathological damages and blocked the increased ALT and AST levels in cold-exposed rats. Moreover, Mdivi-1 inhibited mitochondrial fission and suppressed ferroptosis. Furthermore, SB203580 and Mdivi-1 administration alleviated cold stress-induced liver injury. Our results suggested that cold stress caused liver damage partially by inducing ferroptosis through the p38 MAPK/Drp1 pathway. These findings might provide an effective preventive and therapeutic target for cold stress-induced liver injury.