Primary central nervous system lymphoma: a series report and literature review.

OBJECTIVE: This study aims to analyze the clinical features, Radiological findings and diagnostic characteristics (tissue biopsy, flow cytometry and cerebrospinal fluid cytology) of primary central nervous system lymphoma (PCNSL). To improve the diagnosis of the disease. METHODS: A total of 19 patients with primary central nervous system lymphoma admitted to the Second Hospital of Hebei Medical University from 2014 to 2023 were selected. The clinical data of the patients were retrospectively analyzed. Combined with the relevant literature, the clinical characteristics of PCNSL patients were analyzed to assist the diagnosis. RESULT: Most of the patients were middle-aged and elderly patients (65 years old), and the main clinical manifestations showed no obvious specificity, including headache, dizziness and limb weakness. Radiological findings showed that common site of currence were located in the brain parenchyma. The PCNSL subtype of 19 patients was all diffuse large B cell subtype by cytology, flow cytometry or histopathology. Six cases were diagnosed by biopsy pathology and 11 cases were diagnosed by flow cytometry of cerebrospinal fluid. In all patients diagnosed with PCNSL by clinical cytology (CSF cytology and flow cytometry), abnormal cells were found on CSF examination. CONCLUSION: The pathological type of primary central nervous system lymphoma was diffuse large B-cell subtype, with diverse clinical manifestations and multiple. Both tissue directed biopsy and flow cytometry could effectively assist clinical diagnosis. Early and timely diagnosis and intervention are of great significance for delaying the disease process and reducing the economic burden of patients and families.

Dual-recognition "turn-off-on" fluorescent Biosensor triphenylamine-based continuous detection of copper ion and glyphosate applicated in environment and living system.

Heavy metal Cu2+ emitted in industry and residues of glyphosate pesticides are pervasive in ecosystems, accumulated in water bodies and organisms' overtime, constituting hazard to human and ecological balance. The development of rapid, highly selective, reversibility and sensitive biosensor in vivo detection for Cu2+ and glyphosate was imminent. A novel dual-recognition fluorescence biosensor MPH was successfully synthesized based on triphenylamine, which demonstrated remarkable ratiometric fluorescence quenching toward Cu2+, while MPH-Cu2+ (1:1) ensemble exhibited ratiometric fluorescence restoration for glyphosate, both with observable color changes in daylight and UV lamp. The biosensor exhibited rapid, outstanding selectivity, anti-interference, and multiple cycles reversibility through "turn-off-on" fluorescence towards Cu2+ and glyphosate, respectively. Surprisingly, the clearly binding mechanisms of MPH to Cu2+ and MPH-Cu2+ ensemble to glyphosate were determined, respectively, based on the Job's plot, FT-IR, ESI-HRMS, 1H NMR titration and theoretical calculations of dynamics and thermodynamics. In addition, biosensor MPH demonstrated successful detection of Cu2+ and glyphosate across diverse environmental samples including tap water, extraction solutions of traditional Chinese medicine honeysuckle and soil samples. In the meantime, fluorescence imaging of Cu2+ and glyphosate at both micro and macro scales in various living organisms, such as rice roots, MCF-7 cells, zebrafish, and mice, were successfully achieved. Overall, this work was expected to become a promising and versatile fluorescence biosensor for rapid and reversible detection of Cu2+ and glyphosate both in vitro and vivo.

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.

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.

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.

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.

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.

Design, Synthesis, and Biological Activity Determination of Novel Phenylpyrazole Protoporphyrinogen Oxidase Inhibitor Herbicides Containing Five-Membered Heterocycles.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitor herbicides have attracted widespread attention in recent years as ideal herbicides due to their high efficiency, low toxicity, and low pollution. In this article, 30 phenylpyrazole derivatives containing five-membered heterocycles were designed and synthesized according to the principle of bioelectronic isoarrangement and active substructure splicing. A series of structural characterizations were performed on the synthesized compounds. The herbicide activity in greenhouse was evaluated to determine their growth inhibition effect on weeds, their IC50 value through in vitro PPO enzyme activity measurement was calculated, and target compounds 2i and 3j that have herbicide effects comparable to pyraflufen-ethyl were selected. Crop safety experiments have shown that when the spraying concentration is 300 g of ai/ha, gramineous crops such as wheat, corn, and rice are more tolerant to compound 2i, with wheat exhibiting high tolerance, which is equivalent to the crop safety of pyraflufen-ethyl. Compound 2i can be used as a candidate herbicide for wheat, corn, and paddy fields, and the results are consistent with the cumulative concentration experiment. Molecular docking results showed that compound 2i interacted with the amino acid residue ARG-98 by forming two hydrogen bonds and interacted with the amino acid residue PHE-392 by forming two π-π stacking interactions, indicating that compound 2i has more excellent herbicidal activity than pyraflufen-ethyl and is expected to become a potential lead compound of phenylpyrazole PPO inhibitor herbicides.

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.

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.

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.

A novel isophorone-based fluorescent probe for recognition of Al3+ and its bioimaging in cells and plants.

In this work, a novel isophorone-based fluorescent probe H-1 was designed and synthesized. The probe H-1 could achieve highly selective detection of Al3+ through forming a 1:1 complex, with a recognition mechanism based on intramolecular charge transfer (ICT). The detection limit of the probe H-1 for Al3+ is as low as 8.25 × 10-8 M which was determined by fluorescent titration. It is confirmed that H-1 could be used not only for fluorescence spectrometry to detect Al3+ ions in actual water samples, but also for biological imaging to detect Al3+ ions in cells and plants.

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.

Design, Synthesis, and Herbicidal Activity of Diphenyl Ether Derivatives Containing a Five-Membered Heterocycle.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for discovering novel herbicides, and it causes bleaching symptoms by inhibiting the synthesis of chlorophyll and heme. In this study, the active fragments of several commercial herbicides were joined by substructure splicing and bioisosterism, and a series of novel diphenyl ether derivatives containing five-membered heterocycles were synthesized. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were discussed in detail. The results showed that most compounds had good PPO inhibitory activity, and target compounds containing trifluoromethyl groups tended to have higher activity. Among them, compound G4 showed the best inhibitory activity, with a half-maximal inhibitory concentration (IC50) of 0.0468 µmol/L, which was approximately 3 times better than that of oxyfluorfen (IC50 = 0.150 µmol/L). In addition, molecular docking indicated that compound G4 formed obvious π-π stacking interactions and hydrogen bond interactions with PHE-392 and ARG-98, respectively. Remarkably, compound G4 had good safety for corn, wheat, rice, and soybean, and the cumulative concentration in crops was lower than that of oxyfluorfen. Therefore, compound G4 can be used to develop potential lead compounds for novel PPO inhibitors.

Primary meningeal central nervous system lymphoma: A case report and literature review.

RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and isolated meningeal PCNSL, without evidence of parenchymal involvement, is even less common, occurring in only 10% to 15% of cases. PATIENT CONCERNS: A 65-years-old female presented to our hospital with progressive lower extremity motor dysfunction and blurred vision. The initial neurological examination revealed decreased muscle strength in both lower extremities and sensory dysfunction of lower extremities, saddle area, and buttocks. Brain magnetic resonance imaging showed no abnormalities. Lumbar enhanced magnetic resonance imaging showed T11 to L3 horizontal meningeal enhancement. Cerebrospinal fluid (CSF) cytology revealed lymphoma cells. Immunohistochemistry and flow cytometry of the CSF were performed as auxiliary methods to establish the diagnosis of lymphoma. DIAGNOSES: The patient was diagnosed primary meningeal central nervous system lymphoma. INTERVENTIONS: During hospitalization, the patient was treated with 2 courses of high-dose intrathecal methotrexate and rituximab combined with intrathecal chemotherapy and supportive treatment. OUTCOMES: After 2 years of follow-up, the patient was able to walk and take care of herself. LESSONS: Cases of PCNSL involving only the meninges are rare. Multimodal analysis of the CSF comprises an important component of the diagnostic work-up for patients with primary meningeal central nervous system lymphoma.

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.

A Diagnostic Scoring System for Distinguishing between Tuberculous and Bacterial Meningitis Based on Clinical and Laboratory Findings.

It is very difficult to diagnose and distinguish tuberculous meningitis, and the current laboratory methods are unsubstantial in developing countries. The study is aimed at creating a scoring system on the basis of basic laboratory and clinical achievements that could be used as diagnostic aid for tuberculous meningitis for Chinese patients. A retrospective study of cases was conducted for comparison between clinical characteristics and laboratory features of 241 patients on admission who conformed to inclusion criteria of tuberculous meningitis (n = 141) or bacterial meningitis (n = 100). Logistic regression was employed to establish a diagnostic formula to distinguish between tuberculous meningitis and bacterial meningitis. The receiver operating characteristic curve analysis was applied to determine the best diagnostic critical point of the diagnostic formula. It was found that five variables (disease course, white blood cell count, serum sodium, total white cell count of cerebrospinal fluid, and neutrophil proportion in cerebrospinal fluid) were independently associated with tuberculous meningitis. The 87% sensitivity and 94% specificity were included in the diagnostic scoring system derived from these variables. Especially in the case of limited microbial resources, doctors can use this diagnostic scoring system to distinguish tuberculous meningitis from bacterial meningitis.

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.