Surround Sensing Technique for Trucks Based on Multi-Features and Improved Yolov5 Algorithm.

The traditional rearview mirror method cannot fully guarantee safety when driving trucks. RGB and infrared images collected by cameras are used for registration and recognition, so as to achieve the perception of surroundings and ensure safe driving. The traditional scale-invariant feature transform (SIFT) algorithm has a mismatching rate, and the YOLO algorithm has an optimization space in feature extraction. To address these issues, this paper proposes a truck surround sensing technique based on multi-features and an improved YOLOv5 algorithm. Firstly, the edge corner points and infrared features of the preset target region are extracted, and then a feature point set containing the improved SIFT algorithm is generated for registration. Finally, the YOLOv5 algorithm is improved by fusing infrared features and introducing a composite prediction mechanism at the prediction end. The simulation results show that, on average, the image stitching accuracy is improved by 17%, the time is reduced by 89%, and the target recognition accuracy is improved by 2.86%. The experimental results show that this method can effectively perceive the surroundings of trucks, accurately identify targets, and reduce the missed alarm rate and false alarm rate.

Deciphering biochar compost co-application impact on microbial communities mediating carbon and nitrogen transformation across different stages of corn development.

Under current climatic conditions, developing eco-friendly and climate-smart fertilizers has become increasingly important.The co-application of biochar and compost on agricultural soils has received considerable attention recently.Unfortunately, little is known about its effects on specific microbial taxa involved in carbon and nitrogen transformation in the soil.Herein, we report the efficacy of applying biochar-based amendments on soil physicochemical indices, enzymatic activity, functional genes, bacterial community, and their network patterns in corn rhizosphere at seedling (SS), flowering (FS), and maturity (MS) stages.The applied treatments were: compost alone (COM), biochar alone (BIOC), composted biochar (CMB), fortified compost (CMWB), and the control (no fertilizer (CNTRL).The non-metric multidimensional scaling (NMDS) indicated total nitrogen (TN), pH, NO3--N, urease, protease, and microbial biomass C (MBC) as the dominant environmental factors driving soil bacteria in this study.The dominant N mediating genes belonged to nitrate reductase (narG) and nitronate monooxygenase (amo), while beta-galactosidase, catalase, and alpha-amylase were the dominant genes observed relating to C cycling.Interestingly, the abundance of these genes was higher in COM, CMWB, and CMB compared with the CNTRL and BIOC treatments.The bacteria network properties of CWMB and CMB indicated robust niche overlap associated with high cross-feeding between bacterial communities compared to other treatments.Path and stepwise regression analyses revealed norank_Reyranellaceae and Sphingopyxis in CMWB as the major bacterial genera and the major predictive indices mediating soil organic C (SOC), NH4+-N, NO3--N, and TN transformation.Overall, biochar with compost amendments improved soil nutrient conditions, regulated the composition of the bacterial community, and benefited C/N cycling in the soil ecosystem.

Exploration of ß-glucosidase-producing microorganisms community structure and key communities driving cellulose degradation during composting of pure corn straw by multi-interaction analysis.

Poor management of crop residues leads to environmental pollution and composting is a sustainable practice for addressing the challenge. However, knowledge about composting with pure crop straw is still limited, which is a novel and feasible composting strategy. In this study, pure corn straw was in-situ composted for better management. Community structure of ß-glucosidase-producing microorganisms during composting was deciphered using high-throughput sequencing. Results showed that the compost was mature with organic matter content of 37.83% and pH value of 7.36 and pure corn straw could be composted successfully. Cooling phase was major period for cellulose degradation with the highest ß-glucosidase activity (476.25 µmol·p-Nitr/kg·dw·min) and microbial diversity (Shannon index, 3.63; Chao1 index, 500.81). Significant compositional succession was observed in the functional communities during composting with Streptomyces (14.32%), Trichoderma (13.85%) and Agromyces (11.68%) as dominant genera. ß-Glucosidase-producing bacteria and fungi worked synergistically as a network to degrade cellulose with Streptomyces (0.3045**) as the key community revealed by multi-interaction analysis. Organic matter (-0.415***) and temperature (-0.327***) were key environmental parameters regulating cellulose degradation via influencing ß-glucosidase-producing communities, and ß-glucosidase played a key role in mediating this process. The above results indicated that responses of ß-glucosidase-producing microorganisms to cellulose degradation were reflected at both network and individual levels and multi-interaction analysis could better explain the relationship between variables concerning composting cellulose degradation. The work is of significance for understanding cellulose degradation microbial communities and process during composting of pure corn straw.

Dynamics of fungal species related to nitrogen transformation and their network patterns during cattle manure-corn straw with biochar composting.

Fungi are reputed to play a significant role in the composting matrix as decomposers of recalcitrant organic materials like cellulose and lignin. However, information on the fungi communities' roles in nitrogen transformation under a compost-biochar mixture is scarce. This study investigated shifts in fungal species mediating N transformation and their network patterns in cattle manure-corn straw (CMCS) and CMCS plus biochar (CMCB) composting using high-throughput sequencing data. The results revealed that the addition of biochar altered fungal richness and diversity and significantly influenced their compositions during composting. Biochar also altered the compost fungal network patterns; CMCS had a more complex network with higher positive links than CMCB, suggesting stable niche overlap. The consistent agreement of multivariate analyses (redundancy, network, regression, Mantel and path analyses) indicated that Ciliophora_sp in CMCS and unclassified_norank_Pleosporales in CMCB were the key fungal species mediating total N transformation, whereas Scedosporium_prolificans in CMCS and unclassified_Microascaceae in CMCB were identified as major predictive indices determining NO3--N transformation. Also, Coprinopsis cinerea and Penicillium oxalicum were the predictive factors for NH4+-N transformation in CMCS and CMCB during composting. These results indicated that the effects of biochar on N conversions in composting could be unraveled using multivariate analyses on fungi community evolution, network patterns, and metabolism.

Mouse model of Alzheimer's disease demonstrates differential effects of early disease pathology on various brain regions.

Different parts of the brain are affected distinctively in various stages of the Alzheimer's disease (AD) pathogenesis. Identifying the biochemical changes in specific brain regions is key to comprehend the neuropathological mechanisms in early pre-symptomatic phases of AD. Quantitative proteomics profiling of four distinct areas of the brain of young APP/PS1 mouse model of AD was performed followed by biochemical pathway enrichment analysis. Findings revealed fundamental compositional and functional shifts even in the early stages of the disease. This novel study highlights unique proteome and biochemical pathway alterations in specific regions of the brain that underlie the early stages of AD pathology and will provide a framework for future longitudinal studies. The proteomics data were deposited into the ProteomeXchange Consortium via PRIDE with the identifier PXD019192.

Retinal proteomics of experimental glaucoma model reveal intraocular pressure-induced mediators of neurodegenerative changes.

Current evidence suggests that exposure to chronically induced intraocular pressure (IOP) leads to neurodegenerative changes in the inner retina. This study aimed to determine retinal proteomic alterations in a rat model of glaucoma and compared findings with human retinal proteomics changes in glaucoma reported previously. We developed an experimental glaucoma rat model by subjecting the rats to increased IOP (9.3 ± 0.1 vs 20.8 ± 1.6 mm Hg) by weekly microbead injections into the eye (8 weeks). The retinal tissues were harvested from control and glaucomatous eyes and protein expression changes analysed using a multiplexed quantitative proteomics approach (TMT-MS3). Immunofluorescence was performed for selected protein markers for data validation. Our study identified 4304 proteins in the rat retinas. Out of these, 139 proteins were downregulated (≤0.83) while the expression of 109 proteins was upregulated (≥1.2-fold change) under glaucoma conditions (P ≤ .05). Computational analysis revealed reduced expression of proteins associated with glutathione metabolism, mitochondrial dysfunction/oxidative phosphorylation, cytoskeleton, and actin filament organisation, along with increased expression of proteins in coagulation cascade, apoptosis, oxidative stress, and RNA processing. Further functional network analysis highlighted the differential modulation of nuclear receptor signalling, cellular survival, protein synthesis, transport, and cellular assembly pathways. Alterations in crystallin family, glutathione metabolism, and mitochondrial dysfunction associated proteins shared similarities between the animal model of glaucoma and the human disease condition. In contrast, the activation of the classical complement pathway and upregulation of cholesterol transport proteins were exclusive to human glaucoma. These findings provide insights into the neurodegenerative mechanisms that are specifically affected in the retina in response to chronically elevated IOP.

Biochar reduces nutrient loss and improves microbial biomass of composted cattle manure and maize straw.

In this study, nutrient loss, the direct and indirect relationship between period, compost types, temperature, total nitrogen (TN), nitrate nitrogen (NO3 - -N), ammonium nitrogen (NH4 + -N), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) were investigated during composting of cattle manure-maize straw mixture. This study findings revealed that biochar addition lowered NH4 + -N but did not increase NO3 - -N concentrations unlike no biochar piles during composting. The first-order kinetic models showed that biochar accelerated organic matter (OM) degradation and improved nitrogen mineralization, consequently reducing TN losses by 13.6% and OM losses by 12.66%. Transformation ratio of MBC/MBN, coupled with other chemical components of the entire microbial community, suggested a shift in the microbial succession and diversity during composting from the dominant bacteria and actinomycetes to fungi. The structural equation model and path coefficient revealed temperature to be the main factor mediating the evolution of MBC and MBN in composting. The physicochemical variables, phytotoxicity, and final product quality revealed that biochar incorporation to the composting feedstock is an ideal material for mitigating problems of TN and OM losses in composting and ultimately enhancing the fertility potential of the final compost product.

Differences in distribution of functional microorganism at DNA and cDNA levels in cow manure composting.

Denitrification and nitrification processes are the two prominent pathways of nitrogen (N) transformation in composting matrix. This study explored the dynamics of denitrifying and nitrifying bacteria at different composting stages of cow manure and corn straw using functional gene sequencing at DNA and cDNA levels. Corresponding agreement among OTUs, NMDS, mental test and network analyses revealed that functional bacteria community compositions and responses to physicochemical factors were different at DNA and cDNA levels. Specifically, some OTUs were detected at the DNA level but were not observed at cDNA level, differences were also found in the distribution patterns of nitrifying and denitrifying bacteria communities at both levels. Furthermore, co-occurrence network analysis indicated that Pseudomonas, Paracoccus and Nitrosomonas were identified as the keystone OTUs at the DNA level, while Paracoccus, Agrobacterium and Nitrosospira were keystone OTUs at the cDNA level. Mantel test revealed that TN, C/N and moisture content significantly influenced both the denitrifying bacteria and ammonia-oxidizing bacteria (AOB) communities at the DNA level. NO3--N, NH4+-N, TN, C/N, and moisture content only registered significant correlation with the nosZ-type denitrifiers and ammonia-oxidizing bacteria (AOB) communities at the cDNA level. Structural equation model (SEM) showed that TN, NH4+-N, and pH were direct and significantly influenced the gene abundance of denitrifying bacteria. Howbeit, TN, NH4+-N, and NO3--N had significant direct effects on amoA gene abundance.

Bacterial community succession in dairy manure composting with a static composting technique.

This study applied high-throughput sequencing technology and PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved state) to examine the microbial population dynamics during the composting of dairy manure and rice straw in a static (without turning) composting system. The results showed that the composition of the bacterial community varied significantly during the composting process. The dominant phyla included Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Chloroflexi. Biodiversity indices showed that bacterial community diversity had the peak value during the mesophilic phase. Redundancy analysis indicated that nitrogen was the most important factor in the distribution of genera during the composting process. Finally, the Pearson correlation results suggested that Thermomonospora and Thermopolyspora could be the biomarkers of the composting maturation phase. The metabolic characteristics of the bacterial communities were predicted by PICRUSt. The result showed that metabolism of amino acids, lipids, and most of the carbohydrates increased during the whole composting treatment. However, methane metabolism, carbon fixation pathways in prokaryotes, and nucleotide metabolism decreased after the thermophilic phase. The present study provides a better understanding for bacterial community composition and function succession in dairy manure composting.

Correlation between ammonia-oxidizing microorganisms and environmental factors during cattle manure composting.

Cattle manure composting was performed in an aerated vessel. Community structure and diversity of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) were investigated using polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE) techniques targeting the ammonia monooxygenase alpha subunit (amoA) gene and the correlation between AOB and AOA communities and environmental factors was explored. Thirteen (13) AOB sequences were obtained, which were closely related to Nitrosomonas spp., Nitrosomonas eutropha, and Nitrosospira spp. and uncultured bacteria, among which Nitrosomonas spp. were predominant. Excessively high temperature and high ammonium concentration were not favorable for AOB growth. Five AOA sequences, belonging to CandidatusNitrososphaera gargensis and to an uncultured archaeon, were obtained. During composting, community diversity of AOB and AOA fluctuated, with AOA showing a higher Shannon-Wiener index. The AOB community changed more dramatically in the mesophilic stage and the early thermophilic stage, whereas the most obvious AOA community succession occurred in the late thermophilic stage, the cooling stage and the maturity stage. Water content, total nitrogen (TN) and ammonium concentration were more relevant to the AOB community structure, while higher correlations were observed between ammonia, nitrate and TN and the AOA community. AOB community diversity was negatively correlated with pH (r = -0.938, p < 0.01) and water content (r = -0.765, p < 0.05), while positively correlated with TN (r = 0.894, p < 0.01). AOA community diversity was negatively correlated with ammonium concentration (r = -0.901, p < 0.01). Ammonium concentration played an important role in the succession of AOB and AOA communities during composting.

Diversity and abundance of denitrifiers during cow manure composting.

Diversity and abundance of the denitrifying genes nirK, nirS and nosZ were investigated in cow manure compost using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time quantitative PCR (qPCR), respectively. These three genes were detected in all the stages of the composting process. Phylogenetic analysis showed that the nirK gene was closely related to Rhizobiales, Burkholderiales, the nirS gene was closely related to Pseudomonadales and Burkholderiales, and the nosZ gene was closely related to Rhodospirillales, Rhizobiales, Pseudomonadales, and Alteromonadales. qPCR results showed that the abundance of these three genes (nirK, nirS and nosZ) reached the peak value in the late thermophilic stage of composting and abundance of the nirK gene was higher than that of the nosZ gene and the nirS gene. Redundancy analysis (RDA) showed that the diversity of the nirK and nirS genes was significantly correlated with ammonium (p<0.05), the diversity of the nosZ gene was significantly correlated with pH (p<0.05) and the abundance of the nirK nirS and nosZ genes was significantly correlated with temperature (p<0.05).

Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture.

Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Cotreatment regimens combining CBD and DNA-damaging agents produced synergistic antiproliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little to no therapeutic window when considering NPCs.

Prophylactic treatment with the tricyclic antidepressant desipramine prevents development of paclitaxel-induced neuropathic pain through activation of endogenous analgesic systems.

Neuropathic pain impacts approximately 3-4.5% of the global population and remains an unresolved health problem. The management of neuropathic pain has two distinct goals-prevention of development and control of established neuropathic pain. We examined the impact of both prophylactic and therapeutic treatments with the tricyclic antidepressant desipramine on the development and maintenance of toxic neuropathic pain induced by the chemotherapeutic agent paclitaxel. We also investigated the involvement of endogenous analgesic (i.e., endogenous opioid and endocannabinoid) systems in the antinociceptive actions of desipramine in these two distinct phases of neuropathic pain. Chronic subcutaneous infusion of desipramine via osmotic pumps suppressed both the development and maintenance of paclitaxel-induced neuropathic pain. However, only prophylactic desipramine treatment blocked the development of neuropathic pain throughout the three month observation interval; neuropathic pain did not return. The opioid receptor antagonist naloxone blocked the antinociceptive effects of both prophylactic and therapeutic desipramine treatments throughout the entire timecourse of desipramine-induced antinociception. By contrast, cannabinoid CB1 and CB2 receptor antagonists partially attenuated the antinociceptive actions of desipramine in a manner that was restricted to the development phase of paclitaxel-induced neuropathic pain only. Paclitaxel decreased cell viability in TMD231 tumor cells in an MTT assay in vitro. Notably, desipramine (1nM-1µM) alone did not alter tumor cell viability and did not prevent the cytotoxic effects of paclitaxel under identical conditions. The highest concentration of desipramine (10µM) reduced tumor cell viability alone and enhanced the cytotoxic effects of paclitaxel. Our study identifies a previously unrecognized preemptive analgesic strategy that prevents development of paclitaxel-induced neuropathic pain, and also dissects receptor mechanisms underlying desipramine-induced antinociceptive effects. This information may be applied to improve current therapeutic strategies with the goal of preventing and managing neuropathic pain induced by chemotherapeutic treatment.

CB1 Knockout Mice Unveil Sustained CB2-Mediated Antiallodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.

Cannabinoids suppress neuropathic pain through activation of cannabinoid CB1 and/or CB2 receptors; however, unwanted CB1-mediated cannabimimetic effects limit clinical use. We asked whether CP55,940 [(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexanol], a potent cannabinoid that binds with similar affinity to CB1 and CB2 in vitro, produces functionally separable CB1- and CB2-mediated pharmacological effects in vivo. We evaluated antiallodynic effects, possible tolerance, and cannabimimetic effects (e.g., hypothermia, catalepsy, CB1-dependent withdrawal signs) after systemic CP55,940 treatment in a mouse model of toxic neuropathy produced by a chemotherapeutic agent, paclitaxel. The contribution of CB1 and CB2 receptors to in vivo actions of CP55,940 was evaluated using CB1 knockout (KO), CB2KO, and wild-type (WT) mice. Low-dose CP55,940 (0.3 mg/kg daily, i.p. ) suppressed paclitaxel-induced allodynia in WT and CB2KO mice, but not CB1KO mice. Low-dose CP55,940 also produced hypothermia and rimonabant-precipitated withdrawal in WT, but not CB1KO, mice. In WT mice, tolerance developed to CB1-mediated hypothermic effects of CP55,940 earlier than to antiallodynic effects. High-dose CP55,940 (10 mg/kg daily, i.p.) produced catalepsy in WT mice, which precluded determination of antiallodynic efficacy but produced sustained CB2-mediated suppression of paclitaxel-induced allodynia in CB1KO mice; these antiallodynic effects were blocked by the CB2 antagonist 6-iodopravadoline (AM630). High-dose CP55,940 did not produce hypothermia or rimonabant-precipitated withdrawal in CB1KO mice. Our results using the mixed CB1/CB2 agonist CP55,940 document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain. Our study highlights the therapeutic potential of targeting cannabinoid CB2 receptors to bypass unwanted central effects associated with CB1 receptor activation.

Optimization of a cisplatin model of chemotherapy-induced peripheral neuropathy in mice: use of vitamin C and sodium bicarbonate pretreatments to reduce nephrotoxicity and improve animal health status.

BACKGROUND: Cisplatin, a platinum-derived chemotherapeutic agent, produces antineoplastic effects coupled with toxic neuropathic pain and impaired general health status. These side-effects complicate long term studies of neuropathy or analgesic interventions in animals. We recently demonstrated that pretreatment with sodium bicarbonate (4% NaHCO3) prior to cisplatin (3 mg/kg i.p. weekly up to 5 weeks) was associated with improved health status (i.e. normal weight gain, body temperature, creatinine and ketone levels, and kidney weight ratio) in rats (Neurosci Lett 544:41-46, 2013). To reduce the nephrotoxic effects of cisplatin treatment in mice, we compared effects of sodium bicarbonate (4% NaHCO3 s.c.), vitamin C (25 mg/kg s.c.), resveratrol (25 mg/kg s.c.) and saline (0.9% NaCl) pretreatment on cisplatin-induced changes in animal health status, neuropathic pain and proinflammatory cytokine levels in spinal cord and kidney. RESULTS: Cisplatin-treated mice receiving saline pretreatment exhibited elevated ketone, creatinine and kidney weight ratios, representative of nephrotoxicity. Vitamin C and sodium bicarbonate lowered creatinine/ketone levels and kidney weight ratio whereas resveratrol normalized creatinine levels and kidney weight ratios similar to saline pretreatment. All pretreatments were associated with decreased ketone levels compared to saline pretreatment. Cisplatin-induced neuropathy (i.e. mechanical and cold allodynia) developed equivalently in all pretreatment groups and was similarly reversed by either morphine (6 mg/kg i.p.) or ibuprofen (6 mg/kg i.p.) treatment. RT-PCR showed that mRNA levels for IL-1ß were increased in lumbar spinal cord of cisplatin-treated groups pretreated with either saline, NaHCO3 or resveratrol/cisplatin-treated groups. However, IL-6 and TNF-alpha were elevated in the kidneys in all cisplatin-treated groups. Our studies also demonstrate that 60 days after the last cisplatin treatment, body weight, body temperature, kidney functions and mRNA levels have returned to baseline although the neuropathic pain (mechanical and cold) is maintained. CONCLUSIONS: Studies employing cisplatin should include NaHCO3 or vitamin C pretreatment to improve animal health status and reduce nephrotoxicity (lower creatinine and kidney weight ratio) without affecting the development of chemotherapy-induced neuropathy or analgesic efficacy.

Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery.

BACKGROUND: Chemotherapeutic treatment results in chronic pain in an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics an urgent one. We compared the effects of prophylactic cannabinoids as a preventative strategy for suppressing development of paclitaxel-induced nociception. The mixed CB1/CB2 agonist WIN55,212-2 was compared with the cannabilactone CB2-selective agonist AM1710, administered subcutaneously (s.c.), via osmotic mini pumps before, during, and after paclitaxel treatment. Pharmacological specificity was assessed using CB1 (AM251) and CB2 (AM630) antagonists. The impact of chronic drug infusion on transcriptional regulation of mRNA markers of astrocytes (GFAP), microglia (CD11b) and cannabinoid receptors (CB1, CB2) was assessed in lumbar spinal cords of paclitaxel and vehicle-treated rats. RESULTS: Both WIN55,212-2 and AM1710 blocked the development of paclitaxel-induced mechanical and cold allodynia; anti-allodynic efficacy persisted for approximately two to three weeks following cessation of drug delivery. WIN55,212-2 (0.1 and 0.5 mg/kg/day s.c.) suppressed the development of both paclitaxel-induced mechanical and cold allodynia. WIN55,212-2-mediated suppression of mechanical hypersensitivity was dominated by CB1 activation whereas suppression of cold allodynia was relatively insensitive to blockade by either CB1 (AM251; 3 mg/kg/day s.c.) or CB2 (AM630; 3 mg/kg/day s.c.) antagonists. AM1710 (0.032 and 3.2 mg/kg /day) suppressed development of mechanical allodynia whereas only the highest dose (3.2 mg/kg/day s.c.) suppressed cold allodynia. Anti-allodynic effects of AM1710 (3.2 mg/kg/day s.c.) were mediated by CB2. Anti-allodynic efficacy of AM1710 outlasted that produced by chronic WIN55,212-2 infusion. mRNA expression levels of the astrocytic marker GFAP was marginally increased by paclitaxel treatment whereas expression of the microglial marker CD11b was unchanged. Both WIN55,212-2 (0.5 mg/kg/day s.c.) and AM1710 (3.2 mg/kg/day s.c.) increased CB1 and CB2 mRNA expression in lumbar spinal cord of paclitaxel-treated rats in a manner blocked by AM630. CONCLUSIONS AND IMPLICATIONS: Cannabinoids block development of paclitaxel-induced neuropathy and protect against neuropathic allodynia following cessation of drug delivery. Chronic treatment with both mixed CB1/CB2 and CB2 selective cannabinoids increased mRNA expression of cannabinoid receptors (CB1, CB2) in a CB2-dependent fashion. Our results support the therapeutic potential of cannabinoids for suppressing chemotherapy-induced neuropathy in humans.

Apathetic Graves' disease with severe hepatic and renal dysfunction induced by COVID-19 infection: Case report and literature review.

RATIONALE: A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic. PATIENT CONCERN: A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month. DIAGNOSIS: Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy. INTERVENTION: Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy. OUTCOME: After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later. CONCLUSION: COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.

FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury.

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

Metabolic and molecular mechanisms underlying the foliar Zn application induced increase of 2-acetyl-1-pyrroline conferring the 'taro-like' aroma in pumpkin leaves.

Introduction: Fresh pumpkin leaf is popular vegetable for its rich nutrition. The pleasant taro-like odour is important aroma quality of crops, and mostly contributed by 2-acetyl-1-pyrroline in pumpkin. Element Zn can impact metabolite biosynthesis in plants, including aroma formation. However, Zn-induced biochemical responses, especially 2-acetyl-1-pyrroline formation in pumpkin, haven't been elucidated. Methods: This study integrated metabolome and transcriptome to explore molecular fluctuations in pumpkin leaves at different time intervals after foliar Zn treatment. Result and Discussion: We first identified more than one thousand metabolites from pumpkin leaves by integrating different mass spectrometry methods according to the form in which a metabolite exists. Comparative metabolomic analysis revealed there were separately 25 out of 50 and 286 out of 963 metabolites that were respectively identified by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, differentially regulated by Zn treatment. Our findings revealed that 50mg/L of Zn significantly enhanced 2-acetyl-1-pyrroline production by more than 38%, which was contributed by increased biosynthesis of its precursors, including ornithine and proline. The following transcriptome analysis discovered 30,574 genes, including 953 novel genes. Zn treatment induced the differential expression of 41.6% of identified genes which were supposed to regulate the downstream metabolite changes in a time-dependent manner. Pathway analysis indicated that alternations in primary metabolism, including carbon metabolism and biosynthesis of amino acids, were vital to the fluctuated aromatic compound generation. Phytohormones and transcription factors may regulate the expression of gene P5CS and proline biosynthesis, which, therefore, affect 2-acetyl-1-pyrroline production. This research reveals molecular mechanisms of 2-acetyl-1-pyrroline formation in pumpkin, which will provide the molecular basis for desired aroma compound production through metabolite engineering.

Disentangling the coupling relationships between functional denitrifiers and nitrogen transformation during cattle-manure and biochar composting: A novel perspective.

This study explored the coupling relationships between denitrifiers and N-transformation using multi-level (DNA, RNA and enzyme) and multi-aspect (abundance, diversity, structure, key community, network pattern, and functional module) analyses during cattle-manure (CM) and biochar (CMB) composting. Amino sugar-N (ASN, 0.914) and hydrolysable unknown-N (-0.724) were main organic-N components mediating NH4+-N in CM and CMB, respectively. Biochar lowered nirK, nirS, and nosZ genes copies, up-regulated nir gene transcripts, and inhibited nitrite reductase (NIR) activity. For nirK-denitrifiers, Luteimonas was predominant taxa influencing NO2--N and amino acid-N (AAN). Unclassified_k_norank_d_Bacteria and unclassified_p_Proteobacteria regulated NO3--N and ASN, respectively. These three genera played crucial roles in mediating NIR activity and nosZ/nirK. For nirS-denitrifiers, Paracoccus and Pseudomonas mediated NH4+-N and AAN, respectively, and they were vital genera regulating NO3--N, ASN and NIR activity. Furthermore, nirK-denitrifiers was major contributor to denitrification. Overall, functional denitrifiers might simultaneously participate in multiple N-transformation processes.