Construction of Switch Modules for CAR-T Cell Treatment Using a Site-Specific Conjugation System.

Chimeric antigen receptor T-cell (CAR-T cell) therapy has become a promising treatment option for B-cell hematological tumors. However, few optional target antigens and disease relapse due to loss of target antigens limit the broad clinical applicability of CAR-T cells. Here, we conjugated an antibody (Ab) fusion protein, consisting of an Ab domain and a SpyCatcher domain, with the FITC-SpyTag (FITC-ST) peptide to form a bispecific safety switch module using a site-specific conjugation system. We applied the safety switch module to target CD19, PDL1, or Her2-expressing tumor cells by constructing FMC63 (anti-CD19), antiPDL1, or ZHER (anti-Her2)-FITC-ST, respectively. Those switch modules significantly improved the cytotoxic effects of anti-FITC CAR-T cells on tumor cells. Additionally, we obtained the purified CD8+ T cells by optimizing a shorter version of the CD8-binding aptamer to generate anti-FITC CD8-CAR-T cells, which combined with the CD4-FITC-ST switch module (anti-CD4) to eliminate the CD4-positive tumor cells in vitro and in vivo. Overall, we established a novel safety switch module by site-specific conjugation to enhance the antitumor function of universal CAR-T cells, thereby expanding the application scope of CAR-T therapy and improving its safety and efficacy.

Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke.

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

YOLOv5-AC: Attention Mechanism-Based Lightweight YOLOv5 for Track Pedestrian Detection.

In response to the dangerous behavior of pedestrians roaming freely on unsupervised train tracks, the real-time detection of pedestrians is urgently required to ensure the safety of trains and people. Aiming to improve the low accuracy of railway pedestrian detection, the high missed-detection rate of target pedestrians, and the poor retention of non-redundant boxes, YOLOv5 is adopted as the baseline to improve the effectiveness of pedestrian detection. First of all, L1 regularization is deployed before the BN layer, and the layers with smaller influence factors are removed through sparse training to achieve the effect of model pruning. In the next moment, the context extraction module is applied to the feature extraction network, and the input features are fully extracted using receptive fields of different sizes. In addition, both the context attention module CxAM and the content attention module CnAM are added to the FPN part to correct the target position deviation in the process of feature extraction so that the accuracy of detection can be improved. What is more, DIoU_NMS is employed to replace NMS as the prediction frame screening algorithm to improve the problem of detection target loss in the case of high target coincidence. Experimental results show that compared with YOLOv5, the AP of our YOLOv5-AC model for pedestrians is 95.14%, the recall is 94.22%, and the counting frame rate is 63.1 FPS. Among them, AP and recall increased by 3.78% and 3.92%, respectively, while the detection speed increased by 57.8%. The experimental results verify that our YOLOv5-AC is an effective and accurate method for pedestrian detection in railways.

Residue behavior and dietary intake risk assessment of carbosulfan and its metabolites in cucumber.

The residue behavior and dietary intake risks of carbosulfan and its metabolites in cucumbers were investigated. A quick and reliable method for determining carbosulfan and its metabolite residues in cucumbers was established using ultrahigh performance liquid chromatography-tandem mass spectrometry. The fortified recoveries ranged from 87.2% to 91.0% with relative standard deviations of 3.2%-8.1%. The dissipation results showed that carbosulfan was transformed into carbofuran and 3-hydroxy carbofuran in cucumbers. The half-life of carbosulfan was 1.5 days, and the half-life of carbofuran was 45 days. The final residues of carbosulfan varied from 0.245 to 0.005 mg/kg and carbofuran varied from 0.123 to 0.008 mg/kg. After a 5-day application period the residues of carbosulfan was 0.113 mg/kg that was below the maximum residue limit set by China (0.2 mg/kg), and the residues of carbofuran was 0.055 mg/kg that was higher than the maximum residue limit set by China (0.02 mg/kg). The risk assessment results indicated that the dietary intake risks of carbosulfan and carbofuran from cucumber consumption were safe for Chinese consumers, but pre-harvest intervals should be strictly recommended for 7 days at the recommended dose to ensure that food quality conforms to the MRL standard. This study provides a method and data for scientifically evaluating dietary intake risks of carbosulfan and its more toxic metabolites.

Determination of oxathiapiprolin concentration and dissipation in grapes and soil by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

BACKGROUND: The residue concentrations and dissipation rate of a new oxathiapiprolin fungicide in grapes and soil were investigated to provide an evaluation for the safe use of oxathiapiprolin in grapes. Pesticide residue was extracted by acetonitrile, then purified by solid-phase extraction with an Envi-Carb cartridge and determined by ultrahigh-performance liquid chromatography-tandem mass spectrometry. RESULTS: The fortified recoveries ranged from 85.2% to 99.0%, with relative standard deviations of 1.7-4.5%. The limit of quantitation for oxathiapiprolin in grapes and soil was 0.002 mg kg-1 . The mean initial deposits of oxathiapiprolin in grapes were 0.345-0.565 mg kg-1 , with half-lives of 8.6-9.2 days. The mean initial deposits of oxathiapiprolin in soil were 0.078-0.273 mg kg-1 , with half-lives of 7.6-12.0 days. The oxathiapiprolin residue in grapes and soil was 0.002-0.022 mg kg-1 and 0.002-0.123 mg kg-1 when sampling 14 days after application, respectively. CONCLUSION: The residue in the grapes was less than 0.01 mg kg-1 when sampling 28 days after application, which suggested that the application rate of 20 mg a.i. kg-1 for this fungicide should be used to ensure that treated grapes can be considered safe for humans to consume when sampling 28 days after the final application. © 2016 Society of Chemical Industry.

Inhibition of GPR137 suppresses proliferation of medulloblastoma cells in vitro.

Medulloblastoma is the most common malignant pediatric brain tumor in children. GPR137 is a ubiquitously expressed gene in the central nervous system. It has been reported that GPR137 modulates malignant proliferation of glioma cells. However, the relationship between GPR137 and medulloblastoma is still unknown. In this study, we knocked down GPR137 in the medulloblastoma cell line Daoy via a lentivirus-based RNA interference system to explore its role in medulloblastoma. Functional analyses showed that cell proliferation and colony formation were obviously restrained in Daoy cells after GPR137 knockdown. Furthermore, knockdown of GPR137 in Daoy cells led to a significant increase in cell percentage in the G0/G1 phase but a decrease in the S phase. Additionally, the cell population in the sub-G1 phase, which represents apoptotic cells, was remarkably increased in GPR137 knockdown cells. GPR137 inhibition induced a strong proapoptotic effect in Daoy cells, as confirmed by annexin V-APC/7-AAD double staining. In conclusion, GPR137 knockdown inhibited growth of Daoy medulloblastoma cells via disturbing cell cycle progression and inducing apoptosis. Our investigation suggested that GPR137 could be a potential oncogene in medulloblastoma cells and might serve as a target for the treatment of medulloblastoma.

Clinical and imaging characteristics of growing skull fractures in children.

Growing skull fracture (GSF) is an uncommon form of head trauma among young children. In prior research, the majority of GSFs were typically classified based on pathophysiological mechanisms or the duration following injury. However, considering the varying severity of initial trauma and the disparities in the time elapsed between injury and hospital admission among patients, our objective was to devise a clinically useful classification system for GSFs among children, grounded in both clinical presentations and imaging findings, in order to guide clinical diagnosis and treatment decisions. The clinical and imaging data of 23 patients less than 12 years who underwent GSF were retrospectively collected and classified into four types. The clinical and imaging characteristics of the different types were reviewed in detail and statistically analyzed. In all 23 patients, 5 in type I, 7 in type II, 8 in type III, and 3 in type IV. 21/23 (91.3%) were younger than 3 years. Age ≤ 3 years and subscalp fluctuating mass were common in type I-III (P = 0.026, P = 0.005). Fracture width ≥ 4 mm was more common in type II-IV (P = 0.003), while neurological dysfunction mostly occurred in type III and IV (P < 0.001).Skull "crater-like" changes were existed in all type IV. 10/12 (83.3%) patients with neurological dysfunction had improved in motor or linguistic function. There was not improved in patients with type IV. GCS in different stage has its unique clinical and imaging characteristics. This classification could help early diagnosis and treatment for GCS, also could improve the prognosis significantly.

One-stop hybrid operation versus microsurgery for treating brain arteriovenous malformation in children-a retrospective case series.

Background: Brain arteriovenous malformation (BAVM) is one of the most common causes of cerebral hemorrhage in children. The effectiveness of one-stop hybrid operation in the treatment of BAVM in adults has been widely confirmed, but there are few study for the case in children. The aim of this study was to retrospectively analyze of the role and significance of one-stop hybrid surgery versus microsurgery in the treatment of BAVM in children. Methods: A total of 57 children (≤18 years old) with BAVM who were admitted to The 900th Hospital and Fujian Children's Hospital between September 2018 and August 2022 were retrospectively analyzed. According to the inclusion and exclusion criteria, 38 patients were included, and they were divided into a microsurgical group (25 patients) and a hybrid operation group (13 patients) according to the treatment modality. The following clinical characteristics were observed: sex, age, initial symptoms, presence or absence of signs, Glasgow Coma Scale (GCS) score, Hunt-Hess grade, imaging characteristics such as the location of the BAVM, Spetzler-Martin (S-M) grade, presence of intraventricular hemorrhage, treatment and prognostic indicators such as intraoperative blood loss, operation time, imaging cure, postoperative complications, length of hospital stay, and 3- and 6-month modified Rankin score (mRS) after the operation. Results: The proportions of female patients (P=0.042), patients whose BAVM were located in the supratentorial region (P=0.034) and patients whose S-M grade was above grade III (P=0.003) were greater in the hybrid operation group than those in the microsurgical group. The intraoperative blood loss (P<0.001), operation time (P<0.001) and postoperative hospital stay (P=0.024) of patients in the microsurgical group were greater than those in the hybrid operation group. The presence of signs and the S-M grade may be relevant factors in predicting the surgical approach, and the probability of selecting a hybrid operation for each step of increasing the S-M grade was 3.046 times that of microsurgery. Conclusions: A one-stop hybrid operation is effective and safe for the treatment of BAVM in children. High S-M grades of BAVM are more suitable for hybrid operation.

Spinal MCP-1 Contributes to Central Post-stroke Pain by Inducing Central Sensitization in Rats.

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.

Residues and dietary risk assessment of fluazinam in root mustard after field experiments.

The residue levels of fluazinam in root mustard were investigated by using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique with ultra-performance liquid chromatography tandem mass spectrometry. Samples of leaf and root mustard were analyzed. The recoveries of fluazinam were 85.2-110.8% for leaf mustard with the coefficient of variation of 1.0-7.2%, and 88.8-93.3% for root mustard with the coefficient of variation of 1.9-12.4%. The suspension concentrate formulation of fluazinam was applied on root mustard at 262.5 g a.i. ha-1 in accordance with good agricultural practice (GAP), respectively. After the final application, the root mustard samples were collected at 3, 7, and 14 days. Fluazinam residues in root mustard were less than 0.01-0.493 mg kg-1. The dietary risk of fluazinam was predicted by comparing intake amounts with the toxicological data, namely acceptable daily intake (ADI) and acute reference dose (ARfD). The risk quotient (RQ) was 72.2-74.3%, for ordinary consumers, which showed negligible risk. According to the maximum residue limit (MRL) and dietary risk assessment, it is suggested that the pre-harvest interval (PHI) of 3 days; meanwhile, the MRL of 2 mg kg-1 was suggested for fluazinam in root mustard, which indicates that the dietary risk of fluazinam 500 g L-1 suspension concentrate (SC) with the recommended usage on root mustard is negligible. This study provided basic data on the use and safety of fluazinam in root mustard to help the Chinese government formulate a maximum residue level for fluazinam in root mustard.

Bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap technique for nonsyndromic unilateral coronal synostosis.

Background: The goals of operative treatment for unilateral coronal synostosis (UCS) are to improve appearance and allow unrestricted brain growth. However, for severe unilateral premature closure of the coronal suture, existing methods do not address the compression of the brain or expand the volume of the skull cavity. We report our retrospective experience with bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap (CVR + FFBF) technique and the resulting changes in the anterior cranial vault asymmetry index (ACVAI) and intracranial volume. Methods: Twenty patients with UCS who underwent bilateral fronto-orbital advancement combined with CVR + FFBF technique from April 2014 to May 2019 were included. Surgical efficacy was evaluated by the ACVAI and intracranial volume before the operation, 1 week after the operation, and at the last follow-up (average 19.8 months; range, 12 to 40 months). The measurement data are presented as the mean ± standard deviation and were statistically analyzed by t-test. Results: The ACVAI was 9.07%±3.55% before the operation, 3.56%±3.42% 1 week after the operation, and 3.13%±2.41% at the last follow-up. The ACVAI 1 week after the operation was significantly lower than that before the operation (t=4.827, P<0.001). There was no significant difference between the ACVAI 1 week after the operation and at the last follow-up (t=0.660, P=0.517). The intracranial volume was 1,027.85±112.25 mL in patients before the operation and 1,131.92±161.71 mL in the normal control group, which was a statistically significant difference (t=2.364, P=0.023). The intracranial volume significantly increased 1 week after surgery: 1,081.62±111.10 mL (t=8.703, P<0.001), and this trend continued at the last follow-up (1,386.90±119.30 mL) similarly to the normal control group (1,438.22±89.28 mL). At the last follow-up, there was no significant difference between the two groups (t=1.540, P=0.132). Conclusions: For the treatment of UCS, bilateral fronto-orbital advancement combined with CVR + FFBF technique offers functional and cosmetic outcomes in terms of intracranial volume expansion and fronto-orbital symmetry.

Stereoscopic virtual reality models for planning tumor resection in the sellar region.

BACKGROUND: It is difficult for neurosurgeons to perceive the complex three-dimensional anatomical relationships in the sellar region. METHODS: To investigate the value of using a virtual reality system for planning resection of sellar region tumors. The study included 60 patients with sellar tumors. All patients underwent computed tomography angiography, MRI-T1W1, and contrast enhanced MRI-T1W1 image sequence scanning. The CT and MRI scanning data were collected and then imported into a Dextroscope imaging workstation, a virtual reality system that allows structures to be viewed stereoscopically. During preoperative assessment, typical images for each patient were chosen and printed out for use by the surgeons as references during surgery. RESULTS: All sellar tumor models clearly displayed bone, the internal carotid artery, circle of Willis and its branches, the optic nerve and chiasm, ventricular system, tumor, brain, soft tissue and adjacent structures. Depending on the location of the tumors, we simulated the transmononasal sphenoid sinus approach, transpterional approach, and other approaches. Eleven surgeons who used virtual reality models completed a survey questionnaire. Nine of the participants said that the virtual reality images were superior to other images but that other images needed to be used in combination with the virtual reality images. CONCLUSIONS: The three-dimensional virtual reality models were helpful for individualized planning of surgery in the sellar region. Virtual reality appears to be promising as a valuable tool for sellar region surgery in the future.

Insight into the uptake, accumulation, and metabolism of the fungicide phenamacril in lettuce (Lactuca sativa L.) and radish (Raphanus sativus L.).

The fungal species Fusarium can cause devastating disease in agricultural crops. Phenamacril is an extremely specific cyanoacrylate fungicide and a strobilurine analog that has excellent efficacy against Fusarium. To date, information on the mechanisms involved in the uptake, accumulation, and metabolism of phenamacril in plants is scarce. In this study, lettuce and radish were chosen as model plants for a comparative analysis of the absorption, accumulation, and metabolic characteristics of phenamacril from a polluted environment. We determined the total amount of phenamacril in the plant-water system by measuring the concentrations in the solution and plant tissues at frequent intervals over the exposure period. Phenamacril was readily taken up by the plant roots with average root concentration factor ranges of 60.8-172.7 and 16.4-26.9 mL/g for lettuce and radish, respectively. However, it showed limited root-to-shoot translocation. The lettuce roots had a 2.8-12.4-fold higher phenamacril content than the shoots; whereas the radish plants demonstrated the opposite, with the shoots having 1.5 to 10.0 times more phenamacril than the roots. By the end of the exposure period, the mass losses from the plant-water systems reached 72.0% and 66.3% for phenamacril in lettuce and radish, respectively, suggesting evidence of phenamacril biotransformation. Further analysis confirmed that phenamacril was metabolized via hydroxylation, hydrolysis of esters, demethylation, and desaturation reactions, and formed multiple transformation products. This study furthers our understanding of the fate of phenamacril when it passes from the environment to plants and provides an important reference for its scientific use and risk assessment.

Residue behavior and risk assessment of pyraclostrobin and tebuconazole in peppers under different growing conditions.

This study evaluates the residue behavior and risks of pyraclostrobin and tebuconazole in peppers. An analytical method for the simultaneous determination of the concentration of these fungicides in peppers was developed using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry. Pepper samples were extracted with acetonitrile and cleaned with primary secondary amine and graphitized carbon black. The average recoveries of pyraclostrobin and tebuconazole under three fortification levels were 86.7-101.4% and 81.7-104.4%, with relative standard deviations of 4.0-7.2% and 3.8-10.9%, respectively. The limit of quantification of both fungicides in peppers was 0.01 mg/kg. The terminal residue trial of 30% pyraclostrobin and tebuconazole suspension concentrate was investigated for samples cultivated in open fields and greenhouses. The results showed that the terminal residues of pyraclostrobin and tebuconazole in peppers were lower than the maximum residue limits established by GB 2763-2021 (0.5 mg/kg for pyraclostrobin and 2 mg/kg for tebuconazole). The results of a statistical t-test indicated that there was no significant difference between samples grown in open fields and greenhouses. According to the international estimate of short-term intake (IESTI) calculation model, provided by the Joint FAO/WHO Meeting on Pesticide Residues, the acute dietary exposure risk of both fungicides in peppers was acceptable for the general population, with an IESTI of 0-3% and 0-5% of the acute reference dose for pyraclostrobin and tebuconazole, respectively.

Ropivacaine-induced seizures evoked pain sensitization in rats: Participation of 5-HT/5-HT3R.

Due to the increasing use of local anesthetic techniques in various healthcare settings, local anesthetic toxicity still occurs. Seizures are the most common symptom of local anesthetic toxicity. The relationship between local anesthetic-induced seizures and the sensation of pain has not been established till now. Here, we assessed the development of pain hypersensitivity after ropivacaine-induced seizures (RIS) and the influence of RIS on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. In addition, the involvement of spinal 5-HT/5-HT3R in RIS-induced pain sensitization was investigated. According to a sequential exploratory experimental strategy, we first calculated the 50% seizure dosage of ropivacaine to be 42.66 mg/kg (95% confidence interval: 40.19-45.28 mg/kg). We showed that RIS induced significant bilateral mechanical pain hypersensitivity that lasted around 5 days, accompanied by an increase in spinal 5-HT. Moreover, RIS considerably protracted postsurgical pain and enhanced formalin-induced spontaneous flinching in the second phase. Depletion of spinal 5-HT with intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT) reduced RIS-induced pain hypersensitivity and prevented the prolonging of postsurgical pain following RIS. Likewise, blocking spinal 5-HT3R by intrathecal administration of ondansetron reversed RIS-induced pain hypersensitivity and attenuated the pronociception of RIS in the formalin test. Our findings revealed that acute RIS led to pain hypersensitivity and had pronociceptive effects on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. Moreover, our data implied that RIS-induced pain sensitization depends on spinal 5-HT/5-HT3R signaling. Thus, targeting the descending serotonergic facilitation system should be an important element of the precise treatment for local anesthetic toxicity.

Determination of thiamethoxam and its metabolite clothianidin residue and dissipation in cowpea by QuEChERS combining with ultrahigh-performance liquid chromatography-tandem mass spectrometry.

The dissipation and residue levels of thiamethoxam and its metabolite clothianidin in cowpea were investigated under field conditions. Samples of cowpea were analyzed using a QuEChERS technique with ultra-performance liquid chromatography tandem mass spectrometry. The recoveries were 86.5-118.9% for thiamethoxam and 75.6-104.1% for clothianidin, with the coefficient of variation of < 13%. The water dispersible granule formulation of thiamethoxam was applied on cowpea at 30 and 45 g active ingredient ha-1 in accordance with good agricultural practice. The half-life of thiamethoxam in cowpea was 0.8-1.6 days. The cowpea samples were gathered at 3, 7, and 10 days after the last application, and the residues of thiamethoxam in cowpea were < 0.005-0.054 mg kg-1, while those of clothianidin were < 0.005-0.008 mg kg-1. The final residues of thiamethoxam and clothianidin were below the European Union (EU) maximum residue level (0.3 mg kg-1 for thiamethoxam; 0.2 mg kg-1 for clothianidin) in cowpea after a preharvest interval (PHI) of 7 days. This study provided basic data on the use and safety of thiamethoxam and clothianidin in cowpea to help the Chinese government formulate a maximum residue level for thiamethoxam in cowpea.

Uptake, Translocation, and Biotransformation of Neonicotinoid Imidaclothiz in Hydroponic Vegetables: Implications for Potential Intake Risks.

Imidaclothiz is a novel and systemic neonicotinoid pesticide with excellent insecticidal efficacy. However, knowledge of its uptake, translocation, and biotransformation within plants is still largely unknown, restricting work on its accurate and comprehensive risk assessment. Here, we systematically investigated the behavior of imidaclothiz in three plant-water systems via hydroponic experiments. The results showed that imidaclothiz was readily taken up by plant roots and translocated upward, resulting in relative enrichment in leaves. The recoveries of imidaclothiz in plant-water systems decreased with increasing exposure time, and approximately 31.8-45.6% mass loss was measured at the end of exposure. Ultimately, imidaclothiz yielded five products in celery leaves, three products in lettuce leaves, and two products in radish leaves. Multiple metabolic reactions including hydroxylation, hydrolysis of nitrate ester, and methylation occurred within plants. This is the first report on the fate of imidaclothiz within plants and suggests increasing concerns about the risk assessment of imidaclothiz.

Occurrence and dietary risk assessment of 37 pesticides in wheat fields in the suburbs of Beijing, China.

The co-occurrence of multiple pesticides in wheat fields adversely affects human health and the environment. Herein, 206 pairs of wheat and soil samples were collected from wheat fields in Beijing, China from 2018 to 2020. One or multiple pesticide residues were detected, and carbendazim (maximum: 38511.5 µg/kg) and tebuconazole (maximum: 45.4 µg/kg) had heavy occurrence in the wheat samples. Carbendazim, triazoles, and neonicotinoids were frequently detected in the soil samples. HCHs and DDTs were detected, with p,p'-DDE in 100.0% of the soil samples at a maximum concentration of 546.0 µg/kg in 2020. Concentrations of carbendazim, tebuconazole, hexaconazole, and cyhalothrin in the paired soil and wheat samples exhibited significant positive correlations. Pesticides that exceeded the maximum residue limits do not pose non-carcinogenic risks, with one exception. The results provide important references towards risk monitoring and control in wheat fields, as well as facilitating the scientific and reasonable use of these pesticides.

[Study on the adsorption behavior of nickel on potassium tetratitanate whisker by flame atomic absorption spectrometry].

The adsorption behavior of Ni (II) on potassium tetratitanate whisker was studied systemically by FAAS, seeing about the reasons for absorption, disentanglement and the effect of interfering ions on the recovery. The preconcentration method was simple, quick and had good selectivity. The adsorption rate of Ni(II) by potassium tetratitanate whisker was 100% at pH 5.0 and Ni(II) could be eluted from potassium tetratitanate whisker with hydrochloric acid (C: 0.5 mol x L(-1)), shake time exceeding 5 min, stick time exceeding 1.5 h, and the disentanglement ratio exceeding 90%. The relative standard deviation (RSD) was 2.6%. The results obtained indicate that the potassium tetratitanate whisker has good regenerate capability.