Large variations of dissolved carbon occurred in small ponds within an agricultural watershed.

Dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) significantly affect the aquatic carbon budget and ecosystem functions. Small ponds are abundant globally and widely distributed especially in agricultural watersheds, however, the variability of DOC and DIC, along with their driving factors, remains poorly understood, which likely hampers the understanding of carbon cycle of inland waters. The presented study was designed to fill the knowledge gap based on a detailed year-long field investigation via examining DOC and DIC concentrations across ponds with differing functionalities (e.g. sewage ponds, irrigation ponds, and natural ponds) of a typical agricultural watershed in eastern China. Our results found a pronounced impact of human activities on pond DOC and DIC, with higher DOC occurring in sewage ponds (10.84 ± 2.83 mg L-1) and irrigation ponds (9.09 ± 2.57 mg L-1) and peak DIC in irrigation ponds (20.36 ± 2.49 mg L-1) compared to that at natural ponds (DOC: 7.54 ± 2.55 mg L-1; DIC: 11.16 ± 3.85 mg L-1) with less human activity. The positive correlations between DOC/DIC and key environmental variables (e.g. nutrients and chlorophyll-a) further demonstrated that human activity can either directly increase the carbon concentrations via pollutant discharge, or indirectly increase DOC concentration via stimulating primary production. Meanwhile, field measurements found precipitation and temperature play roles in determining the carbon variability. Specifically, precipitation increased the DOC of these ponds via enhancing land-based carbon inputs, and decrease the DIC of irrigation ponds via diluting. Temperature can influence the carbon dynamics through increasing primary productivity and metabolism. Our study underscores the roles of human and natural influences in determining the large variations of DOC and DIC in small ponds, which should be considered to better understand the carbon dynamic variability of human-impacted small aquatic systems.

sgRNA structure optimization and PTG/Cas9 system synergistically boost gene knockout efficiency in an insect.

Knockouts mediated by CRISPR/Cas9 technology are widely used to study insect gene functions, but the efficiency in Hemiptera is low. New strategies are urgently needed to improve gene knockout efficiency. This study initially explored the impact of modifying the fundamental backbone structure of single guide RNA (sgRNA) on knockout efficiency. The results indicated that both in vitro and in vivo transcription of sgRNA structures (Loop5bp + MT/C type) increased average knockout efficiency by 0.61-fold compared to the original sgRNA. In addition, the PTG/Cas9 system was observed to induce a 0.64-fold increase in average knockout efficiency using the original sgRNA. Notably, an integrated PTG/Cas9 system (iPTG/Cas9 system), the integration of optimized sgRNA structures (Loop5bp + MT/C type) into the conventional PTG/Cas9 system, demonstrated a synergistic effect, resulting in a 1.45-fold increase in average knockout efficiency compared to the original sgRNA structure. The iPTG/Cas9 system was effectively used to simultaneously knockout two different target sites within a single gene and to co-knockout two genes. This study represents the first application of the iPTG/Cas9 system to establish a double knockout system in Hemiptera, offering a promising approach to enhance knockout efficiency in species with low efficiency and improve genetic manipulation tools for pest control.

Glufosinate-ammonium increased nitrogen and phosphorus content in water and shaped microbial community in epiphytic biofilm of Hydrilla verticillata.

Glufosinate-ammonium (GLAM) can be released into adjacent water bodies with rainfall runoff and return water from farmland irrigation. However, impacts of GLAM on aquatic organisms remain unclear. In this study, changes in water quality, plant physiological parameters and epiphytic microbial community were investigated in wetlands with Hydrilla verticillata exposed to GLAM for 24 days. We found GLAM addition damaged cell and reduced chlorophyll a content in Hydrilla verticillata leaves, and increased ammonium and phosphorus in water (p < 0.001). The α-diversity increased in bacterial community but decreased in eukaryotic community with GLAM exposure. Neutral community models explained 62.3 % and 55.0 % of the variance in bacterial and eukaryotic communities, respectively. Many GLAM micro-biomarkers were obtained, including some clades from Proteobacteria, Bacteroidete, Actinobacteriota, Phragmoplastophyta, Annelida and Arthropoda. Redundancy analysis revealed that GLAM concentration was positively correlated to Flavobacterium, Gomphonema and Closterium but negatively to Methyloglobulus and Methylocystis. Network analysis revealed that 15 mg/L GLAM disturbed the interactions among phytoplankton, protozoa, metazoan and bacteria and reduced the stability of the microbial communities compared to 8 mg/L GLAM. GLAM shaped the nitrogen and phosphorus cycle related bacterial genes. This study highlights that herbicides are non-neglectable factors affecting the efficiency of aquatic ecological restoration in agricultural areas to control agricultural non-point source pollution.

Association of hidradenitis suppurativa (HS) with waist circumference: A bidirectional two-sample Mendelian randomization study of HS with metabolic syndrome.

Observational studies have suggested an associations between hidradenitis suppurativa (HS) and metabolic syndrome (MetS) and its components. However, it remains unclear whether the relationship is causal or not. Our study aimed to investigate the causal association of HS with MetS and its components. We performed a bidirectional, two-sample Mendelian randomization study using summary-level data from the most comprehensive genome-wide association studies of HS (n = 362 071), MetS (n = 291 107), waist circumference (n = 462 166), hypertension (n = 463 010) fasting blood glucose (FBG, n = 200 622), triglycerides (n = 441 016), and high-density lipoprotein cholesterol (HDL-C, n = 403 943). Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms associated with the corresponding factors. The random-effects inverse-variance weighted method was applied as the primary method. The results showed that genetically predicted HS was positively associated with waist circumference risk in both directions. High waist circumference increased the risk of HS (odds ratio [OR] 4.147; 95% confidence interval [CI] 2.610-6.590; p = 1.746 × 10-9). In addition, HS was also affected by waist circumference (OR 1.009; 95% CI 1.006-1.012; p = 3.08 × 10-7). No causal relationships were found between HS and MetS or its components other than waist circumference. The findings highlight the importance of early intervention for obesity in HS patients. Further studies are needed to determine the pathophysiology of HS associated with MetS and its components.

Efficacy of Lacticaseibacillus paracasei fermented milk on a model of constipation induced by loperamide hydrochloride in BALB/c mice.

Currently, most studies focus on the functions of probiotic-fermented milk, whereas there are relatively few studies on the function of postbiotic-fermented milk in relieving constipation. In this study, we aimed to assess the modulation of constipation symptoms and its mechanism of action by different concentrations of Lacticaseibacillus paracasei-fermented milk as a postbiotic in a loperamide hydrochloride-induced constipation model in BALB/c mice. By comparing the relevant indexes, colon histological analysis, gene expression level, and intestinal flora structure in the constipation model of mice, we found that high and ultra-high doses of fermented milk can effectively relieve constipation. Fermented milk effectively reduced defecation time, increased the rate of small intestinal propulsion in constipated mice, and alleviated colonic inflammation, safeguarding the normal function of the intestinal tract. In addition, it can regulate the intestinal flora, downregulate the abundance of Proteobacteria, upregulate the abundance of species of Firmicutes and Actinobacteriota, and improve the overall abundance level of intestinal flora in mice.

Au@Pd nanozyme-mediated catalytic therapy: a novel strategy for targeting tumor microenvironment in cancer treatment.

BACKGROUND: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations. METHODS: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood. RESULTS: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects. CONCLUSIONS: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells.

Dual attention based fusion network for MCI Conversion Prediction.

Alzheimer's disease (AD) severely impacts the lives of many patients and their families. Predicting the progression of the disease from the early stage of mild cognitive impairment (MCI) is of substantial value for treatment, medical research and clinical trials. In this paper, we propose a novel dual attention network to classify progressive MCI (pMCI) and stable MCI (sMCI) using both magnetic resonance imaging (MRI) and neurocognitive metadata. A 3D CNN ShuffleNet V2 model is used as the network backbone to extract MRI image features. Then, neurocognitive metadata is used to guide the spatial attention mechanism to steer the model to focus attention on the most discriminative regions of the brain. In contrast to traditional fusion methods, we propose a ViT based self attention fusion mechanism to fuse the neurocognitive metadata with the 3D CNN feature maps. The experimental results show that our proposed model achieves an accuracy, AUC, and sensitivity of 81.34%, 0.874, and 0.85 respectively using 5-fold cross validation evaluation. A comprehensive experimental study shows our proposed approach significantly outperforms all previous methods for MCI progression classification. In addition, an ablation study shows both fusion methods contribute to the high final performance.

GABAergic Retinal Ganglion Cells Projecting to the Superior Colliculus Mediate the Looming-Evoked Flight Response.

The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.

Distribution of xylan linked glucuronic acid labelled by molecularly imprinted polymers on pulp fiber surface.

Efficiently utilization of plant resources is heavily restricted by the resistance of lignocellulose in plant cells, which is related to the interlinkages of lignocellulose components. Hemicellulose in plant cell wall is bound to cellulose by hydrogen bond and linked with lignin in lignin-carbohydrate complex (LCC). In the xylan chain of hemicellulose, glucuronic acid (GA) is a typical side-group, which provides clues for us to label and locate hemicellulose. The way to label GA on the surface of pulp fibers obtained from pulping process is benefit to explore the deconstruction of lignocellulose. Herein, a new visualization method, fluorescence modified molecularly imprinted polymers (MIP) were applied to recognize and locate GA on the pulp fiber surface. The method combining fluorescence imaging and integrated 3D fiber structure verified the feasibility of the MIP for specific GA recognition. The results showed that xylan (represented by GA) was closely attached to lignin, distributed along the inner wall of pulp fiber cells, and gradually taken off from the inside edge of fiber cells with the deconstruction of lignocellulose. This research provided a basis to develop visualization bioimaging technology to identify biomass components.

Van der Waals mid-wavelength infrared detector linear array for room temperature passive imaging.

Passive imaging for mid-wave infrared (MWIR) is resistant to atmospheric pollutants, guaranteeing image clarity and accuracy. Arrayed photodetectors can simultaneously perform radiation sensing to improve efficiency. Room temperature van der Waals (vdWs) photodetectors without lattice matching have evolved rapidly with optimized stacking methods, primarily for single-pixel devices. The urgent need to implement arrayed devices aligns with practical demands. Here, we present an 8 by 1 black phosphorus/molybdenum sulfide (BP/MoS2) vdWs photodetector linear array with a fill-factor of ~77%, fabricated using a temperature-assisted sloping transfer method. The flat interface and uniform thickness facilitate carrier transport and minimize pixel nonuniformities, showing an average peak detectivity (D*) of 2.34 × 109 cm·Hz1/2·W-1 in the mid-wave infrared region. Compared to a single pixel, push-broom scanning passive imaging is eight times more efficient and further enhanced through mean filtering and fast Fourier transform filtering for strip noise correction. Our study offers guidance on vdWs arrayed devices for engineering applications.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

Phosphodiesterase-5 inhibitors and hearing impairment: a disproportionality analysis using the US food and drug administration adverse event reporting system.

BACKGROUND: This study aimed to investigate the association between phosphodiesterase-5 inhibitors (PDE-5i) and hearing impairment adverse events (HIAEs) while providing an overview of the characteristics of drug-related HIAEs. RESEARCH DESIGN AND METHODS: We conducted a detailed pharmacovigilance analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, covering 2004 to 2022. By calculating the reporting odds ratio (ROR) and the information component (IC), we identified signals that indicate the association between PDE-5i use and HIAEs. RESULTS: Among the 191,398 reports related to PDE-5i, we identified 2,608 cases of HIAEs. Signals were observed for both PDE-5i monotherapy and polytherapy, indicating combinations of drugs. Avanafil exhibited the strongest signal (ROR: 4.35, 95% CI: 2.56-7.41, IC: 2.09, 95% CI: 0.10-3.51), while vardenafil showed the weakest signal (ROR: 2.69, 95% CI: 2.21-3.28, IC: 1.14, 95% CI: 0.74-2.04). Sildenafil had the highest reported cases (ROR: 3.03, 95% CI: 2.82-3.24, IC: 1.57, 95% CI: 1.34-1.80). CONCLUSION: These findings highlight a significant correlation between PDE-5i use and HIAEs, emphasizing the need for careful evaluation in clinical practice and providing appropriate guidance to patients before initiating treatment.

Endosome-microautophagy targeting chimera (eMIATAC) for targeted proteins degradation and enhance CAR-T cell anti-tumor therapy.

Rationale: Since oncogene expression products often exhibit upregulation or abnormally activated activity, developing a technique to regulate abnormal protein levels represent a viable approach for treating tumors and protein abnormality-related diseases. Methods: We first screened out eMIATAC components with high targeted degradation efficiency and explored the mechanism by which eMIATAC induced target protein degradation, and verified the degradation efficiency of the target protein by protein imprinting and flow cytometry. Next, we recombined eMIATAC with some controllable elements to verify the regulatable degradation performance of the target protein. Subsequently, we constructed eMIATAC that can express targeted degradation of AKT1 and verified its effect on GBM cell development in vitro and in vivo. Finally, we concatenated eMIATAC with CAR sequences to construct CAR-T cells with low BATF protein levels and verified the changes in their anti-tumor efficacy. Results: we developed a system based on the endosome-microautophagy-lysosome pathway for degrading endogenous proteins: endosome-MicroAutophagy TArgeting Chimera (eMIATAC), dependent on Vps4A instead of lysosomal-associated membrane protein 2A (LAMP2A) to bind to the chaperone Hsc70 and the protein of interest (POI). The complex was then transported to the lysosome by late endosomes, where degradation occurred similarly to microautophagy. The eMIATACs demonstrated accuracy, efficiency, reversibility, and controllability in degrading the target protein EGFP. Moreover, eMIATAC exhibited excellent performance in knocking down POI when targeting endogenous proteins in vivo and in vitro. Conclusions: The eMIATACs could not only directly knock down abnormal proteins for glioma treatment but also enhance the therapeutic effect of CAR-T cell therapy for tumors by knocking down T cell exhaustion-related proteins. The newly developed eMIATAC system holds promise as a novel tool for protein knockdown strategies. By enabling direct control over endogenous protein levels, eMIATAC has the potential to revolutionize treatment for cancer and genetic diseases.

Designing Dense, Robust, and Ion-Diffusion-Effective Electrodes from Natural Wood Material toward High-Volumetric-Performance Supercapacitors.

Assembling active materials into dense electrodes is a promising way to obtain high-volumetric-capacitance supercapacitors, but insufficient ion channels in the dense structure lead to a low rate capability. Herein, a dense and robust wood electrode with a large MXene volumetric mass loading (1.25 g cm-3) and abundant ion diffusion channels is designed via a facile capillary-force-driven self-densification strategy. Specifically, MXene is assembled onto a wood cell wall, endowing the wood electrode with good electrical conductivity (86 S cm-1) and high electrochemical activity (5.9 F cm-2 at 1 mA cm-2). Notably, the oriented channels along with spaces between adjacent microfibrils recast after densification ensure efficient ion transport for the wood electrode, achieving an excellent rate capability with a high capacitance retention of 77% from 1 to 20 mA cm-2. Meanwhile, the capillary force induces self-densification on the softened wood cell wall, resulting in a highly compact and robust structure for the wood electrode.

Mechanistic insights into lanthipeptide modification by a distinct subclass of LanKC enzyme that forms dimers.

Naturally occurring lanthipeptides, peptides post-translationally modified by various enzymes, hold significant promise as antibiotics. Despite extensive biochemical and structural studies, the events preceding peptide modification remain poorly understood. Here, we identify a distinct subclass of lanthionine synthetase KC (LanKC) enzymes with distinct structural and functional characteristics. We show that PneKC, a member of this subclass, forms a dimer and possesses GTPase activity. Through three cryo-EM structures of PneKC, we illustrate different stages of peptide PneA binding, from initial recognition to full binding. Our structures show the kinase domain complexed with the PneA core peptide and GTPγS, a phosphate-bound lyase domain, and an unconventional cyclase domain. The leader peptide of PneA interact with a gate loop, transitioning from an extended to a helical conformation. We identify a dimerization hot spot and propose a "negative cooperativity" mechanism toggling the enzyme between tense and relaxed conformation. Additionally, we identify an important salt bridge in the cyclase domain, differing from those in in conventional cyclase domains. These residues are highly conserved in the LanKC subclass and are part of two signature motifs. These results unveil potential differences in lanthipeptide modification enzymes assembly and deepen our understanding of allostery in these multifunctional enzymes.

A novel borate phosphor Lu5Ba6B9O27:Ce3+ codoped with Sr2+/Tb3+ for NUV-white light emitting diode application.

At present, there are still challenges in developing highly efficient and thermally stable phosphors for ultraviolet/near ultraviolet-white light emitting diodes (UV/NUV-WLEDs). Herein, we use traditional high-temperature solid-state reactions to prepare blue-emitting phosphors Lu5-xBa6B9O27:xCe3+ (0.1% ≤ x ≤ 3.0%) and Lu4.975Ba6-ySryB9O27:0.5%Ce3+ (0% ≤ y ≤ 20%), and green-emitting phosphors Lu4.975-zBa6B9O27:0.5%Ce3+,zTb3+ (0% ≤ z ≤ 16%), abbreviated as LBB:xCe3+, LBB:0.5%Ce3+,ySr2+ and LBB:0.5%Ce3+,zTb3+, respectively. Upon 340 nm excitation, LBB:Ce3+ exhibits an asymmetric blue emission ranging from 360 nm to 480 nm. Furthermore, the emission intensity of LBB:0.5%Ce3+ increased 4.8-fold without a spectral shift through the partial substitution of Sr2+ for Ba2+. Through constructing the Ce3+ → Tb3+ energy transfer in the LBB structure, the temperature-dependent integral emission intensity at 483 K improved from only 25% to 68% of the intensity at 303 K due to the existence of fast energy transfer from Ce3+ to Tb3+. The related results indicate that LBB:xCe3+, LBB:0.5%Ce3+,ySr2+ and LBB:0.5%Ce3+,zTb3+ phosphors can be used for UV/NUV-WLEDs.

BMP10 accelerated spinal astrocytic activation in neuropathic pain via ALK2/smad1/5/8 signaling.

Background: Astrocytic activation in the spinal dorsal horn contributes to the central sensitization of neuropathic pain. Bone morphogenetic protein (BMP) 10, one of the BMPs highly expressed in the central nervous system, has been demonstrated to have an accelerated effect on astrocytic activation. This study aimed to investigate the functional effects of BMP10 on the activation of astrocytes in the spinal dorsal horn of animal model of neuropathic pain and to explore potential mechanisms involved in this process. Methods: A neuropathic pain mice model was established using the spared nerve injury (SNI). Western blot analysis was performed to detect the expressional levels of BMP10, activin receptor-like receptor 2 (ALK2), Smad1/5/8, phosphorylated Smad1/5/8, and glial fibrillary acidic protein (GFAP). Immunofluorescence staining was used to detect BMP10, ALK2, and GFAP distribution and expression. The behavioral changes in mice were evaluated using paw withdrawal threshold (PWT), thermal withdrawal latency (TWL), and open field test (OFT). The BMP10 siRNA, Smad1 siRNA, BMP10 peptide, and ALK2-IN-2 (ALK2 inhibitor) were intrathecally administrated to mice. A model of lipopolysaccharide (LPS)-stimulated astrocytes was established to investigate the effect of Smad1. The transfection efficiency of siRNAs was detected by western blot and qRT-PCR analysis. Results: BMP10 levels were increased in the L4-6 ipsilateral spinal dorsal horn of SNI mice and particularly elevated in astrocytes. Consistently, GFAP and phosphorylated Smad1/5/8 were upregulated in the L4-6 ipsilateral spinal dorsal horn after SNI, indicating the activation of astrocytes and Smad1/5/8 signaling. An intrathecal injection of BMP10 siRNA abrogated pain hypersensitivity and astrocytic activation in SNI mice. In addition, intrathecal administration of BMP10 peptide evoked pain hypersensitivity and astrocytic activation in normal mice, and this action was reversed by inhibiting the ALK2. Furthermore, targeting Smad1 in vitro with the help of siRNA inhibited the activation of astrocytes induced by LPS. Finally, targeting Smad1 abrogated BMP10-induced hypersensitivity and activation of astrocytes. Conclusion: These findings indicate that the BMP10/ALK2/Smad1/5/8 axis plays a key role in pain hypersensitivity after peripheral nerve injury, which indicates its stimulative ability toward astrocytes.

Unveiling the Presence of Short- and Medium-Chain Chlorinated Paraffins in the Hadal Trenches of the Western Pacific Ocean.

This study delves into the unexplored distribution and accumulation of chlorinated paraffins (CPs), pervasive industrial contaminants used as flame retardants and plasticizers, within the hadal trenches, some of Earth's most isolated marine ecosystems. Analysis of sediments from the Mussau (MS) and Mariana trench (MT) reveals notably high total CP concentrations (∑SCCPs + ∑MCCPs) of 10,963 and 14,554 ng g-1 dw, respectively, surpassing those in a reference site in the western Pacific abyssal plain (8533 ng g-1 dw). In contrast, the New Britain Trench (NBT) exhibits the lowest concentrations (2213-5880 ng g-1 dw), where CP distribution correlates with clay content, δ13C and δ15N values, but little with total organic carbon and depth. Additionally, amphipods from these trenches display varying CP levels, with MS amphipods reaching concerning concentrations (8681-16,138 ng g-1 lw), while amphipods in the MT-1 site show the lowest (4414-5010 ng g-1 lw). These bioaccumulation trends appear to be primarily influenced by feeding behaviors (δ13C) and trophic levels (δ15N). Utilizing biota-sediment accumulation factor values and principal component analysis, we discern that CPs in sediment may come from surface-derived particulate organic matters, while those in amphipods may come from the above carrion. Our findings elucidate the profound impacts of the emerging pollutants on the Earth's least explored marine ecosystems.

Efficacy and safety of combinations of H1 antihistamines in the treatment of urticaria: A scoping review.

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.