Fluoride exposure-induced gut microbiota alteration mediates colonic ferroptosis through N6-methyladenosine (m6A) mediated silencing of SLC7A11.

Fluoride exposure is widespread worldwide and poses a significant threat to organisms, particularly to their gastrointestinal tracts. However, due to limited knowledge of the mechanism of fluoride induced intestinal injury, it has been challenging to develop an effective treatment. To address this issue, we used a series of molecular biology in vitro and in vivo experiments. NaF triggered m6A mediated ferroptosis to cause intestinal damage. Mechanistically, NaF exposure increased the m6A level of SLC7A11 mRNA, promoted YTHDF2 binding to m6A-modified SLC7A11 mRNA, drove the degradation of SLC7A11 mRNA, and led to a decrease in its protein expression, which eventually triggers ferroptosis. Moreover, NaF aggravated ferroptosis of the colon after antibiotics destroyed the composition of gut microbiota. 16 S rRNA sequencing and SPEC-OCCU plots, Zi-Pi relationships, and Spearman correlation coefficients verified that Lactobacillus murinus (ASV54, ASV58, and ASV82) plays a key role in the response to NaF-induced ferroptosis. Collectively, NaF-induced gut microbiota alteration mediates severe intestinal cell injury by inducing m6A modification-mediated ferroptosis. Our results highlight a key mechanism of the gut in response to NaF exposure and suggest a valuable theoretical basis for its prevention and treatment.

Nuclei engineering for even halide distribution in stable perovskite/silicon tandem solar cells.

Wide-bandgap (WBG) absorbers in tandem configurations suffer from poor crystallinity and weak texture, which leads to severe mixed halide-cation ion migration and phase segregation during practical operation. We control WBG film growth insensitive to compositions by nucleating the 3C phase before any formation of bromine-rich aggregates and 2H phases. The resultant WBG absorbers show improved crystallinity and strong texture with suppressed nonradiative recombination and enhanced resistance to various aging stresses. Perovskite/silicon tandem solar cells achieve power conversion efficiencies of 29.4% (28.8% assessed by a third party) in a 25-square centimeter active area and 32.5% in a 1-square centimeter active area. These solar cells retained 98.3 and 90% of the original efficiency after 1301 and 800 hours of operation at 25° and 50°C, respectively, at the maximum power point (AM 1.5G illumination, full spectrum, 1-sun) when encapsulated.

Characterization of a novel SCN5A mutation associated with long QT syndrome and arrhythmogenic right ventricular cardiomyopathy in a family.

Sudden cardiac death represents a significant diagnostic challenge for forensic pathologists, particularly in inherited arrhythmia syndromes or cardiomyopathies resulting from genetic defects. Molecular autopsies can reveal the underlying molecular etiology in such cases. In this study, we investigated a family with a history of sudden cardiac death to elucidate the molecular basis responsible for sudden cardiac death. The proband underwent a comprehensive forensic examination. Family members received thorough clinical evaluations, including electrocardiogram, Holter monitoring, echocardiography, and cardiac magnetic imaging. Whole exome sequencing and genetic analysis were performed on the deceased and her parents. In addition, Western blotting and patch-clamp recordings were employed to evaluate the expression and function of the mutant protein in vitro. Forensic examination diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) as the cause of sudden death. Genetic analysis identified a novel missense mutation in SCN5A (p.V1323L), which was assessed as likely pathogenic by the ACMG guideline. Another family member carrying the mutation manifested long QT syndrome and mild cardiac fibrosis. The cellular electrophysiological study demonstrated that the mutation resulted in an enhanced late sodium current, suggesting it was a gain-of-function mutation. This study characterizes a novel SCN5A mutation that putatively causes long QT syndrome and may contribute to the development of ARVC. Our work expands the pathogenic spectrum of SCN5A variants and underscores the importance of molecular autopsy in sudden death cases, especially in those with suspected genetic disorders.

Transcriptional regulation and functional validation analysis of the McbZIP1 in Mentha canadensis L.

Monoterpenoids are the main components of Mentha canadensis essential oil. Monoterpene biosynthetic pathways have been explored, but the regulatory mechanisms remain unclarified. We identified an abscisic acid (ABA)-inducible A-type basic leucine zipper (bZIP) transcription factor McbZIP1 that was localized in the nucleus and positively regulates monoterpene synthesis. McbZIP1 was expressed in most M. canadensis tissues and was induced under ABA, mannitol, and NaCl treatments. McbZIP1 had transcriptional activity in yeast and the N terminus (amino acids 75-117) was sufficient for transactivation. Yeast one-hybrid and Dual-Luciferase assays showed that McbZIP1 binds to ABA-responsive elements in the promoter region of limonene synthase gene. Yeast two-hybrid and biomolecular fluorescence complementation assays revealed that McbZIP1 interacts with McSnRK2.4. Overexpression of McbZIP1 in peppermint resulted in dramatically up-regulated monoterpene biosynthesis gene levels and increased menthol contents. The results support a transcriptional regulation mechanism in which McbZIP1 serves as a positive regulator of menthol biogenesis. These findings contribute to the molecular mechanism of monoterpenoid biogenesis, which may have uses in genetic engineering and menthol production.

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer.

Distant metastasis is the major cause of death in patients with breast cancer. Epithelial-mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulates metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and MIR539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

Red-light-dependent chlorophyll synthesis kindles photosynthetic recovery of chlorotic dormant cyanobacteria using a dark-operative enzyme.

Chlorosis dormancy resulting from nitrogen starvation and its resuscitation upon available nitrogen contributes greatly to the fitness of cyanobacterial population under nitrogen-fluctuating environments. The reinstallation of the photosynthetic machinery is a key process for resuscitation from a chlorotic dormant state; however, the underlying regulatory mechanism is still elusive. Here, we reported that red light is essential for re-greening chlorotic Synechocystis sp. PCC 6803 (a non-diazotrophic cyanobacterium) after nitrogen supplement under weak light conditions. The expression of dark-operative protochlorophyllide reductase (DPOR) governed by the transcriptional factor RpaB was strikingly induced by red light in chlorotic cells, and its deficient mutant lost the capability of resuscitation from a dormant state, indicating DPOR catalyzing chlorophyll synthesis is a key step in the photosynthetic recovery of dormant cyanobacteria. Although light-dependent protochlorophyllide reductase is widely considered as a master switch in photomorphogenesis, this study unravels the primitive DPOR as a spark to activate the photosynthetic recovery of chlorotic dormant cyanobacteria. These findings provide new insight into the biological significance of DPOR in cyanobacteria and even some plants thriving in extreme environments.

Embolization coils in treating postoperative bronchopleural fistula: a systematic review.

Objective: This study aims to comprehensively evaluate embolization coils in treating postoperative bronchopleural fistula (BPF). Methods: A systematic review based on PubMed, Embase, and The Cochrane Library studies was conducted. All cases receiving embolization coils in treating postoperative BPF were included. The primary outcome was the efficacy of embolization coils in achieving closure of postoperative BPF. Results: 20 patients from 9 studies were included in this systematic review. A median number of 3 (range: 1-10) embolization coils with sealants obtained a complete closure rate of 80% in patients with postoperative BPF with sizes ranging from 2 to 3.1 mm. Three patients with BPF over 3 mm and one with multiple organ failure failed this treatment. Two cases of coil migration were reported without causing respiratory failure or fistula recurrence. Conclusion: Embolization coils might be considered a safe and effective bronchoscopic treatment for small postoperative BPF of less than 3 mm in size. More extensive and rigorous studies are needed to further evaluate and confirm the optimal use of embolization coils in the context of an alternative to surgical repair.

Plugging performance and mechanism of an OBDF oil-absorbing resin (MMA-SMA-St) plugging agent.

To treat the issue of increased resource wastage due to the higher plugging tendencies of oil-based drilling fluids (OBDF) relative to water-based drilling fluids, this study synthesized a ternary composite oil-absorbing resin and optimized its synthesis parameters. The influence of temperature variations on the resin's oil absorption capacity was assessed. Techniques such as infrared spectroscopy, scanning electron microscopy, TGA-DSC measurements, crosslinking degree analysis, contact angle analysis, X-ray photoelectron spectrometry analysis and examination of the resin's plugging mechanism were employed to investigate its molecular structure, oil absorption properties, and plugging efficiency. Additionally, the impact of various synthesis conditions on the oil absorption expansion rate of the oil-absorbing resin was examined. The findings indicate that the resin developed in this research maintains robust oil absorption capabilities at 160 °C, exhibiting an oil absorption expansion rate of 12.5 g g-1. At this temperature, the composite resin particles effectively sealed leaks of widths 0.25, 0.5, and 0.75 µm. Comparative analysis revealed that adding 3% of these resin particles to OBDF significantly enhanced the sealing of fractures. Remarkably, at 160 °C, OBDF amended with resin particles managed to completely seal fractures measuring 0.25 µm. The novelty of this study is attributed to the utilization of styrene for enhancing the resin's rigidity, coupled with the application of octadecyl methacrylate, which contains long-chain alkyl groups, to optimize the oil absorption and expansion characteristics of the oil-absorbing resin.

Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear. We investigated the role of SOX9 in TGF-ß1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast (RTF) cells. SOX9 overexpression adenovirus (Ad-SOX9) and siRNA were transfected into RTF cells. We found that SOX9 expression was up-regulated in RTF cells treated with TGF-ß1. SOX9 overexpression activated fibroblasts and promoted ECM deposition. Silencing SOX9 inhibited cell proliferation, migration, and ECM deposition, induced G2 arrest, and increased apoptosis in RTF cells. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) assays identified MMP10, a matrix metalloproteinase involved in ECM deposition, as a direct target of SOX9, which promotes ECM degradation by increasing MMP10 expression through the Wnt/ß-catenin signaling pathway. Furthermore, in vivo, SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis, as manifested by reduced tracheal stenosis. In conclusion, our findings indicate that SOX9 can drive fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/ß-catenin signaling pathway. The SOX9-MMP10-ECM biosynthesis axis plays an important role in tracheal injury and repair. Targeting SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

Identify the seasonal differences in water quality and pollution sources between river-connected and gate-controlled lakes in the Yangtze River basin.

The river-connected Dongting Lake (DT) and Poyang Lake (PY), and the gate-controlled Taihu Lake (TH) and Chaohu Lake (CH) are the four important lakes in the Yangtze River Basin. The comprehensive Water Quality Index (WQI), the Eutrophication Integrated Index (TLI(Σ)), and the Positive Matrix Factorization (PMF) model were employed to evaluate water quality and the contribution of pollution sources for these lakes. The results show that WQI for all lakes indicated generally good water quality, with DT scoring 73.52-86.18, the highest among them. During the wet season, the eutrophication degree of river-connected lake was medium, and that of gate-controlled lakes was high. The surface runoff and agricultural non-point sources are the main pollution sources for both types of lakes, but their impact is more pronounced in gate-controlled lakes during the wet season. The study provides evidence support for scientific understanding of water quality problems and management strategies in these areas.

MutaPT: A Multi-Task Pre-Trained Transformer for Classifying State of Disorders of Consciousness Using EEG Signal.

Deep learning (DL) has been demonstrated to be a valuable tool for classifying state of disorders of consciousness (DOC) using EEG signals. However, the performance of the DL-based DOC state classification is often challenged by the limited size of EEG datasets. To overcome this issue, we introduce multiple open-source EEG datasets to increase data volume and train a novel multi-task pre-training Transformer model named MutaPT. Furthermore, we propose a cross-distribution self-supervised (CDS) pre-training strategy to enhance the model's generalization ability, addressing data distribution shifts across multiple datasets. An EEG dataset of DOC patients is used to validate the effectiveness of our methods for the task of classifying DOC states. Experimental results show the superiority of our MutaPT over several DL models for EEG classification.

Optimized Adsorption-Catalytic Conversion for Lithium Polysulfides by Constructing Bimetallic Compounds for Lithium-Sulfur Batteries.

Although lithium-sulfur batteries possess the advantage of high theoretical specific capacity, the inevitable shuttle effect of lithium polysulfides is still a difficult problem restricting its application. The design of highly active catalysts to promote the redox reaction during charge-discharge and thus reduce the existence time of lithium polysulfides in the electrolyte is the mainstream solution at present. In particular, bimetallic compounds can provide more active sites and exhibit better catalytic properties than single-component metal compounds by regulating the electronic structure of the catalysts. In this work, bimetallic compounds-nitrogen-doped carbon nanotubes (NiCo)Se2-NCNT and (CuCo)Se2-NCNT are designed by introducing Ni and Cu into CoSe2, respectively. The (CuCo)Se2-NCNT delivers an optimized adsorption-catalytic conversion for lithium polysulfide, benefitting from adjusted electron structure with downshifted d-band center and increased electron fill number of Co in (CuCo)Se2 compared with that of (NiCo)Se2. This endows (CuCo)Se2 moderate adsorption strength for lithium polysulfides and better catalytic properties for their conversion. As a result, the lithium-sulfur batteries with (CuCo)Se2-NCNT achieve a high specific capacity of 1051.06 mAh g-1 at 1C and an enhanced rate property with a specific capacity of 838.27 mAh g-1 at 4C. The work provides meaningful insights into the design of bimetallic compounds as catalysts for lithium-sulfur batteries.

Enhancing sustainability in medical product supply chains: The role of remanufacturing and government subsidies.

This study explores the impact of government subsidies on the production dynamics within the medical product supply chain, particularly focusing on the remanufacturing of medical goods. Amidst the backdrop of the COVID-19 pandemic, which has underscored the critical shortages in medical supplies, our research delves into the adoption of remanufacturing practices by medical product manufacturers as a strategic response to these shortages and environmental concerns. We investigate how government subsidies influence the production volumes of original manufacturers and remanufacturers and examine the competitive interplay between newly manufactured and remanufactured medical products. Through the development of three production game models-Scenario B (manufacturers produce both new and refurbished products), Scenario N (separate production of new and refurbished products by manufacturers and remanufacturers, respectively), and Scenario C (similar to Scenario N but includes a certification fee paid by remanufacturers to original manufacturers)-we analyze the strategies that could mitigate supply deficiencies during medical crises. Our findings indicate that the certification strategy (Scenario C) not only yields the highest total production of medical products but also offers a viable solution to enhance the sustainability of the entire medical production system by alleviating supply chain disruptions. Furthermore, we discuss the managerial implications of our results, emphasizing the potential of a joint remanufacturing strategy to stabilize the supply chain and foster environmental conservation. Lastly, we highlight our study's limitations and suggest future research directions, particularly concerning the variability in product quality and the reliance on government subsidies. This research contributes to a nuanced understanding of green remanufacturing within the pharmaceutical supply chain, offering insights for manufacturers, remanufacturers, and policymakers aiming for sustainable industry practices.

NIR-Remote Selectively Triggered Buprenorphine Hydrochloride Release from Microneedle Patches for the Treatment of Neuropathic Pain.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 µg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

Self-assembling gelatin based delivery of multienzyme activity nanozyme and photosensitizer for ROS storm based cancer therapy.

Nanozymes with multienzyme activity for reactive oxygen species (ROS) generation and intracellular redox imbalance are attractive strategy for cancer therapy. However, it is severely limited by low biocompatibility and catalytic efficiency, hypoxic and high levels of GSH in the tumor microenvironment. To address these issues, a copper doping carbon nanozyme (CC) with multienzyme activity was designed and integrated with photosensitizer Ce6 and gelatin to fabricate ROS amplifier (CCC). Gelatin endowed CCC with good biocompatibility, low hemolysis, and enzyme responsive degradation. CCC with high CAT-like, POD-like, OXD-like, and GSHox-like activities can induce the intracellular ROS storm formation to eliminate the cancer cells. The OXD-like activity and PDT performance mediated 1O2 generation was markedly potentiated by the CAT-like activity of CCC via catalyzing high expression of H2O2 to generate O2. At the same time, a large amount of ·OH were produced through POD-like activity of CCC and GSH was depleted by the GSHox-like activities of CCC, resulting in a destructive ROS storm formation and cellular redox homeostasis disruption. Both in vivo and in vitro experiments showed that CCC displayed satisfactory anti-tumor activity and biocompatibility. Our work provides a novel strategy for the development of nanozyne enhanced photodynamic therapy of cancer.

Culture and Awe: Understanding Awe as a Mixed Emotion.

Recent work is establishing awe as an important positive emotion that offers physical and psychological benefits. However, early theorizing suggests that awe's experience is often tinged with fear. How then, do we reconcile emergent positive conceptualizations of awe with its more fearful elements? We suggest that positive conceptualizations of awe may partially reflect modern Western experiences of this emotion, which make up the majority of participant samples when studying awe. To test whether awe contains more fearful qualities outside of Western cultures, we compared participants' experiences of this emotion in China to those in the United States. In a two-week daily diary study (Study 1), Chinese participants reported greater fear than American participants during experiences of awe, but not a comparison positive emotion. In response to a standardized awe induction (Study 2), Chinese participants reported more fear, whereas American participants reported more positive emotions. Physiological changes in autonomic activity differed by culture only for heart rate, but not skin conductance or respiratory sinus arrhythmia. These findings reveal that awe may be experienced as a more fearful, mixed emotion in China than in the United States and suggest that current positive conceptualizations of awe may reflect a disproportionate reliance on modern Western samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00243-3.

Response of water quality in major tributaries to the difference of multi-scale landscape indicators in Dongting Lake basin, China.

River water quality has been increasingly deteriorated because of the influence of natural process and anthropogenic activities. Quantifying the influence of landscape metrics, namely topography and land use pattern, which encompass land use composition and landscape configuration, across different spatial and seasonal scales that reflect natural process and anthropogenic activities, is highly beneficial for water quality protection. In this study, we focused on investigating the effects of topography, landscape configuration and land use composition on water quality at different spatial scales, including 1-km buffer and sub-watershed, and seasonal scales, including wet and dry season, based on the monthly water quality data in 2016 of Dongting Lake in China. Multivariate statistical analysis of redundancy analysis and partial redundancy analysis was used to quantify the contributions of these factors under different scales. Our results showed that among the three environmental groups, topography made the greatest pure contribution to water quality, accounting for 11.4 to 30.9% of the variation. This was followed by landscape configuration, which accounted for 9.4 to 23.0%, and land use composition, which accounted for 5.9 to 15.7%. More specifically, water body made the greatest contribution to the water quality variation during dry season at both spatial scales, contributing 16.6 to 17.2% of the variation. In contrast, edge density was the primary interpreter of the variability in water quality during wet season at both spatial scales, accounting for 9.9 to 11.1% of the variation. The spatial variability in the influence of landscape metrics on water quality was not markedly distinct. However, these metrics have a minimal impact difference on water quality at the buffer scale and the sub-watershed scale. Moreover, the contribution of landscape configuration varied the most from the buffer to sub-watershed scales, indicating its importance for the spatial scale difference in water quality. The findings of this study offer useful insights into enhancing water quality through improved handling of landscape metrics.