A comparison of clinical features between neurobrucellosis and tuberculous meningitis.

BACKGROUD: This study aims to compare the clinical manifestations, imaging findings, routine tests, biochemistry indicators and cerebrospinal fluid cytology between neurobrucellosis and tuberculous meningitis. The objective is to evaluate the similarities and differences of these two diseases and improve early diagnosis. METHODS: A comprehensive evaluation was conducted by comparing clinical data, imaging results, routine tests findings, biochemistry indicators and cerebrospinal fluid cytology of patients admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from 2019 to 2021. Statistical analysis was applied to identify significant differences and similarities between the two diseases. RESULTS: Preliminary analysis demonstrated both diseases commonly present with symptoms such as fever, headache. However, there were no statistical differences between neurobrucellosis and tuberculous meningitis in early clinical data, imaging results, routine tests findings, biochemistry indicators. Further analysis indicates there is a statistically significantly difference in the lymphocyte ratio and neutrophil ratio in the cerebrospinal fluid between the two groups. CONCLUSIONS: Neurobrucellosis and tuberculous meningitis share similarities in early clinical manifestations, imaging findings and initial cerebrospinal fluid parametes, making early-stage differentiation challenging. The ratio of lymphocytes and neutrophil in the cerebrospinal fluid and a detailed medical history investigation can provide clues for early clinical diagnosis. So the examination of CSF cytology might be a potential to distinguish these two diseases and become a powerful tool in the future.

Genomic alterations of cerebrospinal fluid cell-free DNA in leptomeningeal metastases of gastric cancer.

BACKGROUND: Leptomeningeal metastases (LM) were rare in gastric cancer (GC), and GC patients with LM (GCLM) generally suffer from poor prognosis. Nevertheless, the clinical utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) was underinvestigated in GCLM. METHODS: We retrospectively studied 15 GCLM patients, and all patients had paired primary tumor tissue samples and post-LM CSF samples while 5 patients also had post-LM plasma samples. All samples were analyzed using next-generation sequencing (NGS), and the molecular and clinical features were correlated with clinical outcomes. RESULTS: CSF had higher mutation allele frequency (P = 0.015), more somatic mutations (P = 0.032), and more copy-number variations (P < 0.001) than tumor or plasma samples. Multiple genetic alterations and aberrant signal pathways were enriched in post-LM CSF, including CCNE1 amplification and cell cycle-related genes, and CCNE1 amplification was significantly associated with patients' overall survival (P = 0.0062). More potential LM progression-related markers were detected in CSF samples than in tumor samples, including PREX2 mutation (P = 0.014), IGF1R mutation (P = 0.034), AR mutation (P = 0.038), SMARCB1 deletion (P < 0.001), SMAD4 deletion (P = 0.0034), and TGF-beta pathway aberration (P = 0.0038). Additionally, improvement in intracranial pressure (P < 0.001), improvement in CSF cytology (P = 0.0038), and relatively low levels of CSF ctDNA (P = 0.0098) were significantly associated with better PFS. Lastly, we reported a GCLM case whose CSF ctDNA dynamic changes were well correlated with his clinical assessment. CONCLUSIONS: CSF ctDNA could more sensitively detect molecular markers and metastasis-related mechanisms than tumor tissues in GCLM patients, and our study sheds light on utilizing CSF ctDNA in prognostic estimation and clinical assessment in GCLM.

Cerebrospinal fluid exosomal protein alterations via proteomic analysis of NSCLC with leptomeningeal carcinomatosis.

PURPOSE: Leptomeningeal carcinomatosis (LC) is a rare complication of non-small cell lung cancer (NSCLC) with highly mortality. Cerebrospinal fluid (CSF) as a special kind of tumor microenvironment (TME) better represents alterations than plasma. However, the clinical value of protein profiles of exosome in CSF as liquid biopsy remains unclear. METHODS: In this study, CSF samples of NSCLC patients with (LC group) or without (NSCLC group) LC were collected and compared to patients without tumors (normal group). CSF exosomes were isolated by ultracentrifugation and protein profiles were performed by label-free proteomics. Differentially expressed proteins (DEPs) were detected by bioinformatics tools and verified by parallel reaction monitoring (PRM). RESULTS: A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. Between LC and NSCLC group, 72 DEPs were found among which FN1 demonstrated the highest betweenness centrality (BC) after protein-protein interaction network analysis. CONCLUSION: We investigated the application of label free and PRM based proteomics to detect key proteins related to LC. FN1 may serve as potential indicator to classify LC and NSCLC. Extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are important in the process of LC. These data is promising for early prediction and diagnosis of LC.

Cerebrospinal fluid circulating tumour DNA genotyping and survival analysis in lung adenocarcinoma with leptomeningeal metastases.

PURPOSE: The prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumour DNA (ctDNA) has been proven to be abundantly present in cerebrospinal fluid (CSF); hence, its clinical implication as a biomarker needs to be further verified. METHODS: We conducted a retrospective study of 35 lung adenocarcinoma (LUAD) patients with LM, and matched CSF and plasma samples were collected from all patients. All paired samples underwent next-generation sequencing (NGS) of 139 lung cancer-associated genes. The clinical characteristics and genetic profiling of LM were analysed in association with survival prognosis. RESULTS: LM showed genetic heterogeneity, in which CSF had a higher detection rate of ctDNA (P = 0.003), a higher median mutation count (P < 0.0001), a higher frequency of driver mutations (P < 0.01), and more copy number variation (CNV) alterations (P < 0.001) than plasma. The mutation frequencies of the EGFR, TP53, CDKN2A, MYC and CDKN2B genes were easier to detect in CSF than in LUAD tissue (P < 0.05), possibly reflecting the underlying mechanism of LM metastasis. CSF ctDNA is helpful for analysing the mechanism of EGFR-TKI resistance. In cohort 1, which comprised patients who received 1/2 EGFR-TKIs before the diagnosis of LM, TP53 and CDKN2A were the most common EGFR-independent resistant mutations. In cohort 2, comprising those who progressed after osimertinib and developed LM, 7 patients (43.75%) had EGFR CNV detected in CSF but not plasma. Furthermore, patient characteristics and various genes were included for interactive survival analysis. Patients with EGFR-mutated LUAD (P = 0.042) had a higher median OS, and CSF ctDNA mutation with TERT (P = 0.013) indicated a lower median OS. Last, we reported an LM case in which CSF ctDNA dynamic changes were well correlated with clinical treatment. CONCLUSIONS: CSF ctDNA could provide a more comprehensive genetic landscape of LM, indicating the potential metastasis-related and EGFR-TKI resistance mechanisms of LM patients. In addition, genotyping of CSF combined with clinical outcomes can predict the prognosis of LUAD patients with LM.

Next-generation sequencing in the diagnosis of neurobrucellosis: a case series of eight consecutive patients.

BACKGROUND: Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF. METHODS: Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed. RESULTS: Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1-4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1. CONCLUSION: NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice.

Design, synthesis and biological activity determination of novel phenylpyrazole protoporphyrinogen oxidase inhibitor herbicides.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is the last common enzyme in the biosynthetic pathway in the synthesis of heme and chlorophyll. The high-frequency use of PPO inhibitor herbicides has led to the gradual exposure of pesticide damage and resistance problems. In order to solve this kind of problem, there is an urgent need to develop new PPO inhibitor herbicides. In this paper, 16 phenylpyrazole derivatives were designed by the principle of active substructure splicing through the electron isosterism of five-membered heterocycles. Greenhouse herbicidal activity experiments and in vitro PPO activity experiments showed that the inhibitory effect of compound 9 on weed growth was comparable to that of pyraflufen-ethyl. Crop safety experiments and cumulative concentration experiments in crops showed that when the spraying concentration was 300 g ai/ha, wheat, corn, rice and other cereal crops were more tolerant to compound 9, among which wheat showed high tolerance, which was comparable to the crop safety of pyraflufen-ethyl. Herbicidal spectrum experiments showed that compound 9 had inhibitory activity against most weeds. Molecular docking results showed that compound 9 formed one hydrogen bond interaction with amino acid residue ARG-98 and two π-π stacking interactions with amino acid residue PHE-392, indicating that compound 9 had better herbicidal activity than pyraflufen-ethyl. It shows that compound 9 is expected to be a lead compound of phenylpyrazole PPO inhibitor herbicide and used as a herbicide in wheat field.

Discovery of novel phenoxypyridine as promising protoporphyrinogen IX oxidase inhibitors.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a significant target for the discovery of novel bleaching herbicides. Starting from the active fragments of several known commercial herbicides, a series of PPO inhibitors with diphenyl ether scaffolds were designed and synthesized by substructure splicing and bioisosterism methods. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were measured. The results showed that the novel synthesized compounds have good PPO inhibitory activity, and the IC50 value against corn PPO ranges from 0.032 ± 0.008 mg/L to 3.245 ± 0.247 mg/L. Among all target compounds, compound P2 showed the best herbicidal activity, with a half inhibitory concentration (IC50) of 0.032 ± 0.008 mg/L. In addition, the molecular docking results showed that the benzene ring part of compound P2 can form a π-π stacking with PHE-392, and the trifluoromethyl group and ARG-98 form two hydrogen bonds. Crop safety experiments and cumulative concentration analysis experiments indicated that compound P2 can be used for weed control in rice, wheat, soybean and corn. Therefore, compound P2 can be selected to develop potential lead compounds for novel PPO inhibitors.

Clinical efficacy and safety of different doses of intrathecal methotrexate in the treatment of leptomeningeal carcinomatosis: a prospective and single-arm study.

OBJECTIVE: To investigate the clinical efficacy and safety of different doses of intrathecal methotrexate in the treatment of leptomeningeal carcinomatosis. METHODS: 53 patients admitted to the Second Hospital of Hebei Medical University with leptomeningeal carcinomatosis were recruited. They were divided into two groups: 15-mg-group received 15 mg methotrexate intrathecally, while the other received 10 mg methotrexate. All patients were followed up to 31 December 2020 or until death. Primary endpoint was the response rate. Secondary endpoints were survival and safety. Treatment-related adverse events were recorded. RESULTS: The intrathecal chemotherapy was regularly maintained in 42 cases. Most primary cancers were lung (60.4%), stomach (18.9%) or breast (5.7%). The clinical response rate was higher in the 15 mg group than the 10 mg group (62.5 vs. 34.5%, P = 0.042). In the 15 mg group, two cases showed myelosuppression and one case showed seizures. In the 10 mg group, one patient appeared fever, three patients appeared myelosuppression and one showed leukoencephalopathy. However, there were no serious irreversible adverse reactions in neither of the two groups. In terms of survival, the median survival was 15.7 weeks in the 15 mg group and 27.1 weeks in the 10 mg group (P = 0.116). Multivariate analysis showed that only targeted therapy improved the survival (P < 0.0001, HR = 5.386). CONCLUSION: Increased dose of methotrexate did not prolong the overall survival, but it was more effective in relieving clinical symptoms with no increased adverse reactions. Targeted therapy might improve the survival.

Phenoxypyridine derivatives containing natural product coumarins with allelopathy as novel and promising proporphyrin IX oxidase-inhibiting herbicides: Design, synthesis and biological activity study.

To seek novel and safe protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors with excellent herbicidal activity. A series of novel phenoxypyridine derivatives containing natural product coumarins with allelopathy were designed and synthesized based on bioisosterism and active subunit combination in this research. Compounds W3.1 and W3.4, with the half-maximal inhibitory concentration (IC50) value of 0.02653 mg/L and 0.01937 mg/L, respectively, displayed excellent herbicidal activity in greenhouse. Their herbicidal activity was similar to commercial herbicide oxyfluorfen (IC50 = 0.04943 mg/L). The best field inhibitory effect of compounds W3.1 and W3.4 recorded was at doses of 450 g ai/ha and 300 g ai/ha, respectively. Compound W3.4 had the best herbicidal activity among all the target compounds in this paper. Molecular docking analysis revealed that compounds W3.1 and W3.4 could form a hydrogen bonds with the amino acid AGR-98 and a π-π superposition with the amino acid PHE-398, respectively, which was similar to the oxyfluorfen. The crop selectivity tests results indicated that maize, cotton and soybean showed high tolerance to compound W3.4. Compound W3.4 reduced the Ca and Cb contents of wheat and rice, but had less effect on maize, cotton and soybean. Selectivity of compound W3.4 in maize, cotton and soybean were appeared to be due to reduced absorption of the herbicide compared to wheat and rice. Compound W3.4 deserves further attention as a candidate structure for new herbicides.

Novel phenoxy-(trifluoromethyl)pyridine-2-pyrrolidinone-based inhibitors of protoporphyrinogen oxidase: Design, synthesis, and herbicidal activity.

As important chemical pesticides, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) herbicides play a vital role in weed management. Herein, in a search for novel PPO herbicides, a series of phenoxypyridine-2-pyrrolidinone derivatives were synthesized and their herbicidal activities were tested. To confirm the structures of the newly synthesized compounds, a colorless single crystal of compound 9d was obtained and crystallographic data collected. PPO inhibition experiments showed that most compounds have PPO inhibitory effects. The half-maximal inhibitory concentration (IC50) of compound 9d and oxyfluorfen were 0.041 mg/L and 0.043 mg/L, respectively, which showed compound 9d was the most potent compound. Compound 9d reduced the Chlorophyll a (Chl a) and Chlorophyll b (Chl b) contents of Abutilon theophrasti (A. theophrasti), to 0.306 and 0.217 mg/g, respectively. Crop selectivity experiments and field trial indicated that compound 9d can potentially be used to develop post-emergence herbicides for weed control in rice, cotton, and peanut. Molecular docking studies showed that both oxyfluorfen and compound 9d can enter the PPO cavity to occupy the active site and compete with the porphyrin to block the chlorophyll synthesis process, affect photosynthesis, and eventually cause weed death. Compound 9d was found to be a promising lead compound for novel herbicide development.

Rapid detection of human herpes virus by next-generation sequencing in a patient with encephalitis.

BACKGROUND: The inflammatory or non-inflammatory changes caused by the virus entering the nervous system and related tissues are central nervous system virus infections. Viral infection is a common infectious disease of the central nervous system, of which herpes simplex virus encephalitis is the most common. However, conventional laboratory techniques to detect an infectious agent are difficult to achieve etiological diagnosis. CASE PRESENTATION: Here we present a patient with severe and progressive encephalitis, requiring diagnosis of the specific pathogen to guide clinical treatments. CONCLUSIONS: Application of next-generation sequencing provided a quick and definite diagnosis of the etiology of encephalitis and enabled our patient to be treated appropriately.

Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis.

BACKGROUND: Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC. METHODS: A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time. RESULTS: The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA. CONCLUSIONS: This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.

The therapeutic value of cerebrospinal fluid ctDNA detection by next-generation sequencing for meningeal carcinomatosis: a case report.

BACKGROUND: It is usually very complicated to treat meningeal carcinomatosis, and it is important to treat it as soon as possible. CASE PRESENTATION: The 19-Del mutation was found in the exon for the epidermal growth factor receptor gene in the pleural effusion of a patient on March 11th, 2015. He took 250 mg of oral gefitinib once a day for 11 months beginning in December of 2015. On the 3rd of November 2016, he arrived at the hospital and presented with dizziness, headache and transient blurred vision. At this time, he began to take 4 mg of oral zoledronic acid once a month to prevent bone metastases. The result of a cytology exam of the cerebrospinal fluid showed that the man had meningeal carcinomatosis. The 19-Del mutation and the 20-T790 M mutation in the exon of the epidermal growth factor receptor gene was found by the next generation sequencing of the CSF. Then, he discontinued taking gefitinib and began to take 90-100 mg of oral AZD9291 once a day in November 2016. After adjusting the medication dose based on the NGS, his headache was noticeably reduced, and his condition gradually stabilized. CONCLUSIONS: Cerebrospinal fluid ctDNA detection by next generation sequencing may become a suitable biomarker to monitor clinical treatment response in meningeal carcinomatosis.

Spectrum of Clinical, Neuroimaging, and Cerebrospinal Fluid Features of Adult Neurocutaneous Melanocytosis.

BACKGROUND: Neurocutaneous melanocytosis (NCM) is a poorly understood disease due to its rarity. This study aimed to summarize the characteristics of adult NCM and improve the awareness of this disease. METHODS: The clinical data of 13 adult patients with NCM were retrospectively reviewed, including neuroimages, cerebrospinal fluid (CSF), and histological features. RESULTS: There were 9 males and 4 females. The mean age at symptom onset was 36.5 years. The initial symptoms included intracranial hypertension in 8 patients and seizure in 4 patients. Ten patients had large and/or multiple congenital melanocytic nevi. MRI revealed hydrocephalus and diffuse thickening of the leptomeninges with T1 shortening in all patients. Post-contrast T1-weighted images showed diffuse linear enhancement of the leptomeninges. Lumbar punctures showed increased open pressure, and elevated protein levels and decreased glucose concentrations in CSF. Cells with intracytoplasmic coarse black granules were found in the CSF and were positive for S100, HMB45, and vimentin. Histopathology of the cutaneous lesions and meninges showed melanocytes but no evidence of malignant melanoma. CONCLUSION: Adult NCM patients present a diversity of clinical manifestations. Brain MRI showing diffuse thickening of the leptomeninges with T1 shortening is useful in diagnosing NCM. Heterocellular melanin may be of great value for early diagnosis of NCM in challenging cases.

The gamma-aminobutyric acid-B receptor (GABAB) encephalitis: clinical manifestations and response to immunotherapy.

PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years). The major clinical features include cognitive decline (9/11), epilepsy (10/11), mental and behavioral disorders (6/11), involuntary movement (4/11), sleep disorders (2/11), hearing loss (1/11), disturbance of consciousness (4/11) and fever (3/11). GABA-B receptor antibody was positive in serum and/or cerebrospinal fluid in 11 patients. Small-cell lung cancer was detected in five patients. Electroencephalogram monitoring demonstrated abnormal discharge in 10 cases. Epileptiform activities were found in five patients. Four patients showed abnormality in hippocampal region, parahippocampal gyrus, temporal and occipital lobe on magnetic resonance imaging. Ten patients accepted first-line immune therapy. Five patients with small-cell lung cancer received oncologic treatment. During a median follow-up of 11 months, eight patients showed a good outcome, two patients (cases 8 and 9) with tumors had a poor one and one patient (case 10) died of status epilepticus. CONCLUSION: Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated with GABABR GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early.

Design, Synthesis, and Safener Activity of Novel Methyl (R)-N-Benzoyl/Dichloroacetyl-Thiazolidine-4-Carboxylates.

A series of novel methyl (R)-N-benzoyl/dichloroacetyl-thiazolidine-4-carboxylates were designed by active substructure combination. The title compounds were synthesized using a one-pot route from l-cysteine methyl ester hydrochloride, acyl chloride, and ketones. All compounds were characterized by IR, ¹H NMR, 13C NMR, and HRMS. The structure of 4q was determined by X-ray crystallography. The biological tests showed that the title compounds protected maize from chlorimuron-ethyl injury to some extent. The ALS activity assay showed that the title compounds increased the ALS activity of maize inhibited by chlorimuron-ethyl. Molecular docking modeling demonstrated that Compound 4e competed against chlorimuron-ethyl to combine with the herbicide target enzyme active site, causing the herbicide to be ineffective.

Infective meningitis caused by Phialemonium curvatum.

Infections caused by rarely encountered fungal pathogens have increased in recent decades. Phialemonium species are widely distributed in the environment and are also involved in human infections, affecting both immunocompromised and immunocompetent patients. The present study describes a case of meningitis caused by Phialemonium curvatum.

A novel isophorone-based NIR fluorescent and colormetric probe for Al3+ sensing and its application for living cells and plants imaging.

In this paper, an isophorone-based NIR fluorescent and colormetric probe BDDH for Al3+ was synthesized and characterized, it showed highly selectivity and sensitivity through significant fluorescence enhancement and visible color change towards Al3+. The job plot confirmed that the binding ratio of BDDH with Al3+ was 1:1. Furthermore, the limit of detection (LOD) of Al3+ was determined to be 4.01 × 10-8 M. Moreover, BDDH was successfully applicated in identification of Al3+ in the different water samples, cell imaging in alive MCF-7 cells and plant imaging in soybean roots.

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX, which is a key step in the synthesis of porphyrins in vivo. PPO inhibitors use protoporphyrinogen oxidase as the target and block the biosynthesis process of porphyrin by inhibiting the activity of the enzyme, eventually leading to plant death. In this paper, phenyl triazolinone was used as the parent structure, and the five-membered heterocycle with good herbicidal activity was introduced by using the principle of substructure splicing. According to the principle of bioisosterism, the sulfur atoms on the thiophene ring were replaced with oxygen atoms. Finally, 33 phenyl triazolinones and their derivatives were designed and synthesized, and their characterizations and biological activities were investigated. The in vitro PPO inhibitory activity and greenhouse herbicidal activity of 33 target compounds were determined, and compound D4 with better activity was screened out. The crop safety determination, field weeding effect determination, weeding spectrum determination, and crop metabolism study were carried out. The results showed that compound D4 showed good safety to corn, soybean, wheat, and peanut but poor selectivity to cotton. The field weeding effect of this compound is comparable to that of the commercial herbicide sulfentrazone. The herbicidal spectrum experiment showed that compound D4 had a wide herbicidal spectrum and a good growth inhibition effect on dicotyledonous weeds. Molecular docking results showed that compound D4 forms a hydrogen bond with amino acid residue Arg-98 in the tobacco mitochondria (mtPPO)-active pocket and forms two π-π stacking interactions with Phe-392. This indicates that compound D4 has stronger PPO inhibitory activity. This indicates that compound D4 has wide prospects for development.

Adult spinal cord diffuse midline glioma, H3 K27-altered mimics symptoms of central nervous system infection: a case report.

Diffuse midline gliomas, H3 K27-altered are infiltrative growth gliomas with histone H3K27M mutations. This glioma is more common in the pediatric population, and the prognosis is usually poor. We report a case of diffuse midline gliomas, H3 K27-altered in an adult patient that mimicked symptoms of central nervous system infection. The patient was admitted due to double vision for 2 months and paroxysmal unconsciousness for 6 days. Initially, lumbar puncture showed persistent high intracranial pressure, high protein, and low chlorine. Magnetic resonance imaging showed diffuse thickening and enhancement of meninges and spinal meninges, and later, fever occurred. The initial diagnosis was meningitis. We suspected central nervous system infection, so we started anti-infection treatment, but the treatment was ineffective. The patient's condition gradually worsened, with lower limb weakness and even the consciousness became unclear. A repeat magnetic resonance imaging and positron emission tomography-computed tomography scan showed space-occupying lesions in the spinal cord, which was considered a tumor. Following neurosurgery, pathological tests identified the tumor as diffuse midline gliomas, H3 K27-altered. The patient was recommended for radiotherapy and temozolomide chemotherapy. The patient's condition improved after chemotherapy treatment, and he survived for an additional 6 months. Our case shows that diagnosing diffuse midline gliomas, H3 K27-altered in the central nervous system is complex and can be confused with the clinical characteristics of central nervous system infection. Therefore, clinicians should pay attention to such diseases to avoid misdiagnosis.