A rhodamine-based fluorescent probe used to determine nitroxyl (HNO) in lysosomes.

The reactive nitrogen species (RNS) in lysosomes play a major role during the regulation of lysosomal microenvironment. Nitroxyl (HNO) belongs to active nitrogen species (RNS) and is becoming a potential diagnostic and therapeutic biomarker. However, the complex synthesis routes of HNO in biosystem always hinder the exact determination of HNO in living cells. Here, a rhodamine-based fluorescent probe used to determine nitroxyl (HNO) in lysosomes was constructed and synthesized. 2-(Diphenylphosphino)benzoate was utilized as the sensing unit for HNO and morpholine was chose as the targeting group for lysosome. Before the addition of HNO, the probe displayed a spirolactone structure and almost no fluorescence was found. After the addition of HNO, the probe existed as a conjugated xanthene form and an intense green fluorescence was observed. The fluorescent probe possessed fast response (3 min) and high selectivity for HNO. Furthermore, fluorescence intensity of the probe linearly related with the HNO concentration in the range of 6.0 × 10-8 to 6.0 × 10-5 mol L-1. The detection limit was found to be 1.87 × 10-8 mol L-1 for HNO. Moreover, the probe could selectively targeted lysosome with excellent biocompatibility and had been effectually utilized to recognize exogenous HNO in A549 cells.

An Organic Coordination Manganese Complex as Cathode for High-Voltage Aqueous Zinc-metal Battery.

Aqueous Zn-Mn battery has been considered as the most promising scalable energy-storage system due to its intrinsic safety and especially ultralow cost. However, the traditional Zn-Mn battery mainly using manganese oxides as cathode shows low voltage and suffers from dissolution/disproportionation of the cathode during cycling. Herein, for the first time, a high-voltage and long-cycle Zn-Mn battery based on a highly reversible organic coordination manganese complex cathode (Manganese polyacrylate, PAL-Mn) was constructed. Benefiting from the insoluble carboxylate ligand of PAL-Mn that can suppress shuttle effect and disproportionationation reaction of Mn3+ in a mild electrolyte, Mn3+ /Mn2+ reaction in coordination state is realized, which not only offers a high discharge voltage of 1.67 V but also exhibits excellent cyclability (100 % capacity retention, after 4000 cycles). High voltage reaction endows the Zn-Mn battery high specific energy (600 Wh kg-1 at 0.2 A g-1 ), indicating a bright application prospect. The strategy of introducing carboxylate ligands in Zn-Mn battery to harness high-voltage reaction of Mn3+ /Mn2+ well broadens the research of high-voltage Zn-Mn batteries under mild electrolyte conditions.

Synergistic Poly(lactic acid) Antibacterial Surface Combining Superhydrophobicity for Antiadhesion and Chlorophyll for Photodynamic Therapy.

The problem of nosocomial infections caused by bacterial growth on material surfaces is an urgent threat to public health. Although numerous materials and methods have been explored to fight against infections, the methods are complicated and the materials are slightly toxic. It is highly desirable to develop an antibacterial strategy that kills bacteria effectively without drug resistance and cytotoxicity. Herein, we present a synergistic antibacterial polylactic acid (PLA) surface with superhydrophobic antibacterial adhesion and photodynamic bactericidal activity. Initially, the surface displayed low-adhesion superhydrophobicity and resisted most bacterial adhesion. Furthermore, completely non-toxic chlorophyll possessed excellent photodynamic bactericidal properties under non-toxic visible light, which was incorporated into micro-/nanoscale PLA surfaces. We achieved efficient antibacterial activity using completely non-toxic materials and a facile non-solvent-induced phase separation process. This non-toxic, simple, good biocompatible, and no drug-resistant strategy has great advantages in combating bacterial infections.

Copper-induced oxidative stress, transcriptome changes, intestinal microbiota, and histopathology of common carp (Cyprinus carpio).

Copper (Cu) is a common contaminant in aquatic environments, which could cause physiological dysfunction in aquatic organisms. However, few studies have comprehensively examined the impact of copper toxicity in freshwater fish over the past decade. In this research, the oxidative stress, liver transcriptome, intestinal microbiota, and histopathology of common carp (C. carpio) in response to Cu exposure were studied, by exposing juvenile carp to 0.2 mg/ml Cu2+ for 30 days. The results revealed that Cu2+ could induce significant changes in malondialdehyde (MDA) content and antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)) activity. The changes in antioxidant enzyme activities indicate that Cu can induce oxidative stress by generating reactive oxygen species (ROS) content. RNA-seq analysis of the liver identified 1069 differentially expressed genes (DEGs) after treatment with 2.0 mg/L Cu2+. Among the DEGs, 490 genes were upregulated and 579 genes were downregulated. GO functional enrichment analysis revealed that Cu could affect the fatty acid biosynthetic process, carnitine biosynthetic process, and activity of carboxylic acid transmembrane transporter. Meanwhile, the most significantly enriched KEGG pathway also included the lipid metabolism pathway. In addition, Cu2+ exposure increased bacterial richness and changed bacterial composition. At the phylum level, we found that the ratio of Bacteroidetes to Firmicutes was increased in the treatment carps, which can regulate intestinal epithelium function and reduce inflammation and immune responses. At the genus level, the abundances of 11 genera were significantly altered after exposure to Cu2+. The altered composition of the microbial community caused by Cu exposure may play a useful role in compensation of the intestinal lesions by Cu exposure. Furthermore, we found that Cu2+ exposure could cause histological alterations such as structural damage to the liver and intestines. The results of this research contribute to a better understanding of mechanisms related to Cu toxicity in fish.

Influence of bone anatomical morphology of mandibular molars on dental implant based on CBCT.

BACKGROUND: To apply CBCT to investigate the anatomical relationship between the mandibular molar and alveolar bone, aimed to provide clinical guidelines for the design of implant restoration. METHODS: 201 CBCT data were reevaluated to measure height of the alveolar process (EF), width of the alveolar process (GH), width of the basal bone (IJ), the angle between the long axis of the first molar and the alveolar bone (∠a) and the angle between the long axis of the alveolar bone and basal bone (∠b). The angle and width were measured to determine the implant-prosthodontic classification of the morphology in the left lower first molar (36) and right lower first molar (46). All measurements were performed on the improved cross-sectional images. RESULTS: EF, GH and IJ were measured as (10.83 ± 1.31) mm, (13.93 ± 2.00) mm and (12.68 ± 1.96) mm for 36, respectively; and (10.87 ± 1.24) mm, (13.86 ± 1.93) mm and (12.60 ± 1.90) mm for 46, respectively. No statistical significance was observed in EF, GH, IJ, ∠a and ∠b between 36 and 46 (all P > 0.05). The morphology was divided into three categories including the straight (68.7-69.2%), oblique (19.9-20.4%) and concave types (11%). Each type was consisted of two subcategories. CONCLUSIONS: The proposed classification could provide evidence for appropriate selection and direction design of the mandibular molar implant in clinical. The concave type was the most difficult to implant with the highest risk of lingual perforation. The implant length, width, direction required more attention.

Folium Sennae and emodin reverse airway smooth muscle contraction.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Daily cooking duration and its joint effects with genetic polymorphisms on lung cancer incidence: Results from a Chinese prospective cohort study.

OBJECTIVES: In this study, we conducted a prospective cohort study to investigate the joint effects of daily cooking duration with single nucleotide polymorphisms (SNPs) on lung cancer incidence. MATERIALS AND METHODS: A total of 33,868 individuals recruited in 2013 from Dongfeng-Tongji cohort study were included in our research, in which 5178 participants were genotyped. Daily cooking duration was accessed by questionnaire, and the incident lung cancer cases were confirmed. Fifteen lung cancer related SNPs were selected according to the previous reports. We used the multiple Cox regression models to evaluate the separate and joint effects of daily cooking duration and SNPs on lung cancer incidence. RESULTS: Each 1-h increase in daily cooking duration was associated with a 17% elevated risk of lung cancer incidence [hazard ratio (HR) (95%CI) = 1.17(1.03, 1.33)]. Specifically, subjects with daily cooking duration >2 h/day had a 2.05-fold increased incident risk of lung cancer than those without cooking [HR(95%CI) = 2.05(1.20, 3.53)] (Ptrend = 0.011). The rs2395185 and rs3817963, both located at 6p21.32, were significantly associated with lung cancer incidence. Compared with no cooking subjects with rs2395185GG or rs3817963TT genotype, subjects with daily cooking >2 h/day and carrying rs2395185GT + TT genotypes had a 2.48-fold increased risk of lung cancer [HR(95%CI) = 2.48(1.03, 5.97)], and there were significant joint effects of rs3817963TC + CC with daily cooking 1-2 and >2 h/day [HR(95%CI) = 2.23(1.07, 4.64) and 2.22(1.05, 4.68), respectively]. CONCLUSIONS: Longer daily cooking duration, especially daily cooking >2 h/day, was associated with increased risk of lung cancer. There were significant joint effects of rs2395185 and rs3817963 with daily cooking duration on lung cancer incidence. This study offered a new indicator of cooking related pollution exposure and added new evidence for the joint effects of environment and genetic factors on lung cancer incidence.

Nell-1 Enhances Osteogenic Differentiation of Pre-Osteoblasts on Titanium Surfaces via the MAPK-ERK Signaling Pathway.

BACKGROUND/AIMS: This study aimed to investigate the effect of Nell-1 on the osteogenic behaviors of pre-osteoblasts on titanium (Ti) surfaces and to identify the underlying signaling pathway. METHODS: Nell-1 at different concentrations was added to culture medium to stimulate MC3T3-E1 subclone 14 on Ti surfaces. A CCK-8 colorimetric assay was used to detect cell proliferation. Alkaline phosphatase activity (ALP) assay and enzyme-linked immunosorbent assay (ELISA) were used to evaluate ALP activity and the osteocalcin (OCN) secretion, respectively. Indicators of osteoblastic differentiation were assessed using real-time polymerase chain reaction analysis (RT-PCR). Western blot (WB) assay was used to analyze the expression changes of the osteogenic proteins and the mitogen-activated protein kinase (MAPK) pathway. RESULTS: Nell-1 significantly increased the osteogenic gene and protein expression levels of ALP, OCN, Runx2, osteoprotegerin (OPG), collagen type I (Col-I), and Osterix (Osx) in pre-osteoblasts on Ti surfaces. The optimal concentration of Nell-1 was 100 ng/ ml. In addition, Nell-1 activated ERK and JNK, but not P38, in MC3T3-E1 cells on the Ti surface. Except for ALP and Col-I, the promotive effects of Nell-1 on the expression of osteogenic markers were suppressed by ERK inhibitor U0126. CONCLUSION: Certain concentrations of Nell-1 can promote the osteogenic differentiation of pre-osteoblasts on Ti surfaces by activating the MAPK/ERK signaling pathway.

Dynamic plasmid copy number control for synthetic biology.

Plasmids that replicate independently from chromosomes are valuable genetic tools for biological research. Dynamic control of plasmid copy number facilitates flexible regulation of the gene of interest or the genetic circuit installed in the plasmid. This useful strategy is being integrated into synthetic biology for metabolic reprogramming and biosensing applications.

A Sensitive Ultra-performance Liquid Chromatography-Tandem Mass Spectrometric Method for Determination of Secalonic Acid F in Rat Plasma and Its Application to Pharmacokinetic Study.

Secalonic acid F (SAF) is a fungal secondary metabolite exhibited interesting pharmacological effect. In this study, a simple and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed and validated for the determination of SAF in rat plasma. Emodin was selected as the internal standard (IS), and plasma samples were prepared by liquid-liquid extraction with ethyl acetate. Chromatographic separation was operated on an Agilent SB-C18 column, and the mobile phase was a mixture of 0.5% formic acid in water and methanol (V:V = 20:80) at a flow rate of 0.3 mL/min. Detection was carried out with a 6460 triple-quadrupole mass spectrometer using electrospray ionization in the multiple-reaction monitoring mode. The MS/MS ion transitions monitored were m/z 639.3 â†’ 415.4 and 269.0 â†’ 225.1 for SAF and IS, respectively. Results showed the calibration curve of SAF was linear in the range of 2-500 ng·mL-1 with the correlation coefficient > 0.99. The matrix effect, extraction recovery, dilution effect, intraday and inter-day precision and accuracy were all in acceptable limits. The analytes were also stable under different conditions. The validated method was successfully applied to a pharmacokinetic study after oral administration in Sprague-Dawley rats at a dose of 10 mg/kg.

A coumarin-naphthalimide-based ratiometric fluorescent probe for nitroxyl (HNO) based on an ICT-FRET mechanism.

Nitroxyl (HNO) is an important reactive nitrogen that is associated with various states in physiology and pathology and plays a unique function in living systems. So, it is important to exploit fluorescent probes with high sensitivity and selectivity for sensing HNO. In this paper, a novel ratiometric fluorescent probe for HNO was developed utilizing intramolecular charge transfer (ICT) and fluorescence resonance energy transfer (FRET) mechanisms. The probe selected coumarin as energy donor, naphthalimide as energy receptor and 2-(diphenylphosphino)benzoate as the sensing site for detecting HNO. When HNO was not present, the 2-(diphenylphosphino)benzoate unit of the probe restricted electron transfer and the ICT process could not occur, leading to the inhibition of FRET process as well. Thus, in the absence of HNO the probe displayed the intrinsic blue fluorescence of coumarin. When HNO was added, the HNO reacted with the 2-(diphenylphosphino)benzoate unit of the probe to yield a hydroxyl group which resulting in the opening of ICT process and the occurring of FRET process. Thus, after providing HNO the probe displayed yellow fluorescence. In addition, the probe showed good linearity in the ratio of fluorescence intensity at 545 nm and 472 nm (I545 nm/I472 nm) with a concentration of HNO (0.1-20 µM). The probe processed a detection limit of 0.014 µM and a response time of 4 min. The probe also specifically identified HNO over a wide pH scope (pH = 4.00-10.00), including physiological conditions. Cellular experiments had shown that this fluorescent probe was virtually non-cytotoxic and could be applied for ratiometric sensing of HNO in A549 cells.

A lysosome-located and rhodamine-based fluorescence probe for recognizing hydrogen polysulfide.

Hydrogen polysulfide (H2Sn, n≥2), as a kind of active sulfur species (RSS), has become a hot topic in RSS. It can regulate the biological activity of many proteins through S-sulfhydrylation of cysteine residues (protein Cys-SSH), and has a protective effect on cells. Although there have been some studies on hydrogen polysulfide, its production, degradation pathway and regulation mechanism still need further be researched. In presented study, an original lysosome-localized fluorescent probe for determining H2Sn was developed utilizing rhodamine as the fluorogen. The probe used morpholine as the locating unit of lysosomes and chose 2-fluoro-5-nitrobenzoate as the recognizing group. Before adding H2Sn, the proposed probe displayed a spironolactone structure and emitted very weak fluorescence. After adding H2Sn, a conjugated xanthene was formed and the probe demonstrated green fluorescence. When the H2Sn concentration was varied from 6.0×10-7 mol·L-1 to 10.0×10-5 mol·L-1, the fluorescence intensity of the probe was linearly dependent on the H2Sn concentration. And the detection limit was 1.5×10-7 mol·L-1. The presented probe owned a fast response speed, good selectivity, excellent sensitivity and broad pH work scope. In addition, the probe had been well utilized to sense endogenic and exogenic H2Sn in lysosomes.

Age structure and body size of two Tibetan toad (Bufo tibetanus) populations from different elevations in China.

Understanding how age and body size vary across elevations can provide insights into the evolution of life-history traits in animals. In the present study, we compared the demographic (using skeletochronology) and morphological traits of the Tibetan toad (Bufo tibetanus) between two populations from different elevational habitats (2650 vs. 3930 m). We found that (1) the mean age and body size of females were significantly greater than those of males in both populations; (2) both sexes of toads from the higher elevation tended to be significantly older in age and larger in body size; (3) there was a significant positive relationship between age and body size within each sex of the toad at both elevations; and (4) growth rates varied between the two populations, with the higher rate observed in the lower-elevation population. Our results suggested that factors other than age, such as elevation-associated temperature, influence the observed differences in body size between the two populations. Future research at a broader range of elevations should focus on these factors and evaluate their influence on animal growth patterns.

Engineering Chimeric Chemoreceptors and Two-Component Systems for Orthogonal and Leakless Biosensing of Extracellular γ-Aminobutyric Acid.

Two-component systems (TCSs) sensing and responding to various stimuli outside and inside cells are valuable resources for developing biosensors with synthetic biology applications. However, the use of TCS-based biosensors suffers from a limited effector spectrum, hypersensitivity, low dynamic range, and unwanted signal crosstalk. Here, we developed a tailor-made Escherichia coli whole-cell γ-aminobutyric acid (GABA) biosensor by engineering a chimeric GABA chemoreceptor PctC and TCS. By testing different TCSs, the chimeric PctC/PhoQ showed the response to GABA. Chimera-directed evolution and introduction of the insulated chimeric pair PctC/PhoQ*PhoP* produced biosensors with up to 3.50-fold dynamic range and good orthogonality. To further enhance the dynamic range and lower the basal leakage, three strategies, engineering of PhoP DNA binding sites, fine-tuning reporter expression by optimizing transcription/translation components, and a tobacco etch virus protease-controlled protein degradation, were integrated. This chimeric biosensor displayed a low basal leakage, a large dynamic range (15.8-fold), and a high threshold level (22.7 g L-1). Finally, the optimized biosensor was successfully applied in the high-throughput microdroplet screening of GABA-overproducing Corynebacterium glutamicum, demonstrating its desired properties for extracellular signal biosensing.

Liquid chromatography with tandem mass spectrometric method for determination of 52 antibiotics in human whole blood and urine and application to forensic cases.

PURPOSE: A rapid and reliable method was developed and validated for the simultaneous analysis of 52 antibiotics (cephalosporins, penicillins, carbapenems, lincosamides, quinolones, nitroimidazoles, macrolides, sulfonamides, tetracyclines, glycopeptide) in urine and whole blood by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). METHOD: Analytes were extracted by dilution or protein precipitation and analyzed on an Agilent 1260 HPLC system coupled to an Agilent 6470 Triple Quadrupole Mass Spectrometer. RESULTS: The method attended method validation criteria. The limits of detection were equal or lower than 2.0 ng/mL, whereas the limits of quantification ranged from 0.1 to 10.0 ng/mL, from 0.1 to 5.0 ng/mL, in urine and whole blood, respectively. For all analytes, the bias and intra- and inter-day precision values were less than 14.7%. The ranges of recovery values of all antibiotics were 76.5-124.5% in whole blood and 76.3-121.8% in urine, values of the effects were lower than 25% in two matrices. No evidence of carryover was observed. The study of sample stability showed that almost all analytes were stable at 24 °C for 24 h, all analytes were stable at -20 °C for 14 days and at -80 °C for 30 days. Freeze-thaw cycles stability showed that antibiotics were stable except for imipenem. Autosampler stability study showed that all analytes were stable for 24 h, except for imipenem and amoxicillin. Applicability was proven by analyzing authentic whole blood (n = 86) and urine (n = 79) samples from patients under antibiotics treatment. Therefore, this method was applied to the analysis 3 forensic allergy cases, which were positive for at least one analyte. CONCLUSIONS: A simple, sensitive and high-throughput method for the simultaneous determination of different classes of antibiotics in urine and whole blood samples was developed and applied. This sensitive method was successfully applied to forensic cases.

Calpeptin improves the cognitive function in Alzheimer's disease-like complications of diabetes mellitus rats by regulating TXNIP/NLRP3 inflammasome.

AIMS: Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD-like complications of diabetes mellitus. This work further investigated its underlying mechanism. MATERIALS AND METHODS: Diabetes mellitus rat model was constructed by a high-fat and high-sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro-injected with LV-TXNIP-OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRß, tight junction proteins occludin and ZO-1, calpain-1, calpain-2, APP, Aß, Aß-related, and TXNIP/NLRP3 inflammasome-related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood-brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory-related factors were assessed by enzyme-linked immunosorbent assay. RESULTS: Calpeptin effectively reduced the expression of Calpain-2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR-ß) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aß accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression. CONCLUSIONS: These data demonstrated that calpeptin treatment alleviated AD-like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD-like complications of diabetes mellitus.

Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani.

In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC50 value of 0.039 µg/mL, which was about 20-fold better than that of boscalid (EC50 = 0.799 µg/mL) and 4-fold more potent than fluxapyroxad (EC50 = 0.131 µg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 µg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC50 = 2.04 µM), which was obviously more potent than those of boscalid (IC50 = 7.92 µM) and fluxapyroxad (IC50 = 6.15 µM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.

Burden of oral disorders, 1990-2019: estimates from the Global Burden of Disease Study 2019.

Introduction: The aim of this study was to understand the global incidence and disability-adjusted life years (DALY) of oral disorders by age, gender, region, and Sociodemographic Index (SDI) from 1990 to 2019. Material and methods: The estimated annual percentage change (EAPC) and 95% confidence intervals (CIs) were used to assess the trends in age-standardized incidence and DALY rates from 1990 to 2019. Results: The global age-standardized incidence rate (EAPC = 0.01) of oral disorders increased slightly from 1990 to 2019. From 1990 to 2019, the age-standardized DALY rate decreased in high-SDI (EAPC = -0.43) and high-middle-SDI (EAPC = -0.14) regions, but it showed increasing trends in low-SDI (EAPC = 0.22), low-middle-SDI (EAPC = 0.36), and middle-SDI (EAPC = 0.17) regions. The EAPC in the age-standardized DALY rate was negatively correlated with the regional SDI value (ρ = -0.402, p = 0.001). From 1990 to 2019, the region with the largest increase in age-standardized DALY rate was South Asia (EAPC = 0.67), while the country with the greatest increase in age-standardized DALY rate was India (EAPC = 0.82). Conclusions: From 1990 to 2019, the global age-standardized incidence rate of oral disorders showed a slight increasing trend. It is necessary to control the increase in DALY and the disease burden associated with oral disorders in low-, low-middle-, and middle-SDI regions, such as South Asia, particularly in India.

Association between bilirubin levels and risk of stroke: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between bilirubin levels and stroke risk. DESIGN: Systematic review and meta-analysis, reported in accordance with Meta-analysis Of Observational Studies in Epidemiology guidelines. DATA SOURCES: The PubMed, Embase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure Databases were searched from inception up to 27 February 2022. ELIGIBILITY CRITERIA: Cohort studies assessing the dose-response relationship between bilirubin levels and risk of stroke were eligible for inclusion. There were no language restrictions. DATA EXTRACTION AND SYNTHESIS: All data from eligible studies were collected and assessed by two independent investigators. We generated pooled relative risks (RRs) with 95% CIs. We used a restricted cubic spline model for the dose-response analyses. Subsequent subgroup analyses were conducted according to stroke outcomes, follow-up duration, geographical area and size of the cohort. RESULTS: Nine articles including results from 11 cohort studies with 7835 cases of stroke and 263 596 participants met the inclusion criteria. The summarised RR of stroke comparing the highest and lowest bilirubin level was 0.85 (95% CI 0.72 to 0.99). The dose-response analysis indicated that a 15 µmol/L increment of bilirubin level was associated with an 18% lower risk of stroke (RR=0.82, 95% CI 0.67 to 0.99). For ischaemic stroke, the RR was 0.76 (95% CI 0.58 to 0.99). Significant publication bias was not detected. CONCLUSIONS: Elevated bilirubin levels were associated with a decreased risk of stroke among adults. PROSPERO REGISTRATION NUMBER: CRD42017071497.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes.

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.