Half-dose ticagrelor versus standard-dose clopidogrel in a dual antiplatelet regimen for stent-assisted coiling or flow diversion of unruptured intracranial aneurysms: a cohort study.

BACKGROUND: Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA). METHODS: A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage. RESULTS: Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889). CONCLUSION: Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA.

Low thermal quenching of metal halide-based metal-organic framework phosphor for light-emitting diodes.

Phosphor-converted white light-emitting diodes (PC-WLEDs) have attracted considerable attention in solid-state lighting and display. However, urgent issues of thermal quenching and high cost remain formidable challenges. Herein, a novel metal-organic framework (MOF) phosphor [CdCl2(AD)] was facilely prepared using a mixture of CdCl2 and acridine (AD) under solvothermal conditions. It shows intensive green emission with a long lifetime of 31.88 ns and quantum yield of 65% while maintaining 95% and 84% of its initial emission intensity after remaining immersed in water for 60 days and being heated to 150 °C, respectively. The low thermal quenching of this MOF material is comparable to or can even exceed that of commercial inorganic phosphors. The combination of experiments and theoretical calculations reveals that the alternating arrangement of delocalized AD π-conjugated systems and CdCl2 inorganic chains through strong coordination bonds and π⋯π stacking interactions imparts the MOF phosphor with high thermal stability and optoelectronic performance. The successful fabrication of green and white LED devices by coating [CdCl2(AD)] and/or N630 red phosphor on a 365/460 nm commercial diode chip suggests a promising and potential alternative to commercial phosphors.

Comprehensive Glycomic and Glycoproteomic Analyses of Human Programmed Cell Death Protein 1 Extracellular Domain.

Human programmed cell death protein 1 (hPD-1) is an essential receptor in the immune checkpoint pathway. It has played an important role in cancer therapy. However, not all patients respond positively to the PD-1 antibody treatment, and the underlying mechanism remains unknown. PD-1 is a transmembrane glycoprotein, and its extracellular domain (ECD) is reported to be responsible for interactions and signal transduction. This domain contains 4 N-glycosylation sites and 25 potential O-glycosylation sites, which implicates the importance of glycosylation. The structure of hPD-1 has been intensively studied, but the glycosylation of this protein, especially the glycan on each glycosylation site, has not been comprehensively illustrated. In this study, hPD-1 ECD expressed by human embryonic kidney 293 (HEK 293) and Chinese hamster ovary (CHO) cells was analyzed; not only N- and O-glycosylation sites but also the glycans on these sites were comprehensively analyzed using mass spectrometry. In addition, hPD-1 ECD binding to different anti-hPD-1 antibodies was tested, and N-glycans were found functioned differently. All of this glycan information will be beneficial for future PD-1 studies.

Seroreactivity against Leptospira spp. differs between community cats and privately-owned cats in Hong Kong.

Leptospirosis is a bacterial zoonotic disease of major One Health significance and public health impact globally, with a wide host range including mammals, cetaceans and herpetofauna. This study aimed to determine Leptospira seroprevalence, risk factors for seroreactivity and prevalence of urinary Leptospira shedding among domestic cats in Hong Kong. Microagglutination testing of 22 Leptospira serovars from 20 serogroups was performed on 738 sera from outdoor free-roaming "community" cats (n = 391) and privately-owned (n = 347) cats. Urine from 268 community cats was tested for pathogenic Leptospira DNA by qPCR targeting lipL32. Potential risk factors associated with exposure were assessed using logistic regression. Overall Leptospira seroprevalence was 9.35%. Of 14 serogroups detected, Javanica (4.3%), Djasiman (2.3%) and Australis (1.5%) were most common. Seroreactivity was significantly higher among community (13.3%) than privately-owned cats (4.9%; OR 2.98 [95% CI 1.68-5.25], P < 0.001), especially to Javanica (7.65% of community cats versus 0.58% of privately-owned cats (P < 0.001). Antibody titres to all serogroups ranged from 1:100 to 1:6400 (median 1:200) and were highest for Javanica (median 1:800). Leptospira DNA was detected in urine from 12/268 community cats (4.48%; median load 6.42 × 102 copies/mL urine; range 1.40 × 101-9.63 × 104). One in three seroreactive community cats with paired urine and blood samples had leptospiruria. After adjusting for source, none of breed, sex, neuter status, age, district rodent infestation rate, serum alanine transaminase or creatinine values were associated with seroreactivity. Cats in Hong Kong are exposed to a diversity of Leptospira serogroups and can shed Leptospira silently in urine. The higher seroprevalence among outdoor free-roaming community cats highlights the importance of environmental drivers in leptospirosis transmission and risks of exposure for sympatric human populations. Gloves should be worn when handling feline urine to minimise the risk of zoonotic transmission from subclinically infected cats.

Long-Term Outcomes of Restorelle® Direct Fix Anterior Mesh in the Treatment of Pelvic Organ Prolapse.

Objective The objective of this study was to evaluate the efficacy and long-term outcomes of the use of Restorelle® Direct Fix (Coloplast, Humlebæk, Denmark) anterior mesh for transvaginal surgical management of anterior compartment prolapse. Methods A retrospective case series review was conducted for 123 patients who underwent surgery for Baden-Walker Grade three and four anterior compartment prolapse with the Restorelle Direct Fix anterior mesh between July 1, 2017 and September 30, 2018 in a single center. Follow-up was conducted at one, six, 12, 24, and 36 months after treatment. A standardized questionnaire and pelvic examination were conducted at each visit to assess operative complications and subjective and objective cure rates. Results Sixty patients were included in the analysis with a three-year follow-up rate of 70.0%. At three years post-operatively, subjective and objective cure rates were 97.7% and 95.3% respectively. Seven (11.7%) patients complained of de novo stress urinary incontinence, four (6.7%) complained of de novo urge urinary incontinence and one (1.7%) complained of symptomatic recurrence. Significantly, six (10.0%) patients had transvaginal mesh exposure over the three-year follow-up, mostly presenting within the first year. One (2.4%) patient developed new asymptomatic mesh erosion at the 36-month visit and one patient required mesh loosening one month post-surgery. Conclusions Management of anterior compartment prolapse with transvaginal surgery using the Restorelle® Direct Fix anterior mesh was associated with good subjective and objective cure rates. However, significant rates of post-operative mesh exposure were noted within three years post-surgery, which hinders the recommendation of this device for augmentation of repair for anterior compartment prolapse.

The predictors to self-reported and performance-based physical function in knee osteoarthritis patients: a cross-sectional study.

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

Iridium(III) carbene complexes as potent girdin inhibitors against metastatic cancers.

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 µM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.

Identification of metabolic components of carotid plaque in high-risk patients utilizing liquid chromatography-tandem mass spectrometry.

OBJECTIVE: Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. METHOD: Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. RESULTS: A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. CONCLUSIONS: Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.

[Two cases of cytopenia associated with multiple malformations]. / 血细胞减少伴多发畸形2例.

The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.

Matrix mechanics regulates muscle regeneration by modulating kinesin-1 activity.

Sarcopenia, a prevalent muscle disease characterized by muscle mass and strength reduction, is associated with impaired skeletal muscle regeneration. However, the influence of the biomechanical properties of sarcopenic skeletal muscle on the efficiency of the myogenic program remains unclear. Herein, we established a mouse model of sarcopenia and observed a reduction in stiffness within the sarcopenic skeletal muscle in vivo. To investigate whether the biomechanical properties of skeletal muscle directly impact the myogenic program, we established an in vitro system to explore the intrinsic mechanism involving matrix stiffness control of myogenic differentiation. Our findings identify the microtubule motor protein, kinesin-1, as a mechano-transduction hub that senses and responds to matrix stiffness, crucial for myogenic differentiation and muscle regeneration. Specifically, kinesin-1 activity is positively regulated by stiff matrices, facilitating its role in transporting mitochondria and enhancing translocation of the glucose transporter GLUT4 to the cell surface for glucose uptake. Conversely, the softer matrices significantly suppress kinesin-1 activity, leading to the accumulation of mitochondria around nuclei and hindering glucose uptake by inhibiting GLUT4 membrane translocation, consequently impairing myogenic differentiation. The insights gained from the in-vitro system highlight the mechano-transduction significance of kinesin-1 motor proteins in myogenic differentiation. Furthermore, our study confirms that enhancing kinesin-1 activity in the sarcopenic mouse model restores satellite cell expansion, myogenic differentiation, and muscle regeneration. Taken together, our findings provide a potential target for improving muscle regeneration in sarcopenia.

Asymmetrical Interactions between Ni Single Atomic Sites and Ni Clusters in a 3D Porous Organic Framework for Enhanced CO2 Photoreduction.

3D porous organic frameworks, which possess the advantages of high surface area and abundant exposed active sites, are considered ideal platforms to accommodate single atoms (SAs) and metal nanoclusters (NCs) in high-performance catalysts; however, very little research has been conducted in this field. In the present work, a 3D porous organic framework containing Ni1 SAs and Nin NCs is prepared through the metal-assisted one-pot polycondensation of tetraaldehyde and hexaaminotriptycene. The single metal sites and metal clusters confined in the 3D space created a favorable micro-environment that facilitated the activation of chemically inert CO2 molecules, thus promoting the overall photoconversion efficiency and selectivity of CO2 reduction. The 3D-NiSAs/NiNCs-POPs, as a CO2 photoreduction catalyst, demonstrated an exceptional CO production rate of 6.24 mmol g-1 h-1, high selectivity of 98%, and excellent stability. The theoretical calculations uncovered that asymmetrical interaction between Ni1 SAs and Nin NCs not only favored the bending of CO2 molecules and reducing the CO2 reduction energy, but also regulated the electronic structure of the catalyst leading to the optimal binding strength of intermediates.

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

A new freshwater species of Pinnularia (Bacillariophyta) from Hunan Province, China.

This study describes a new species of Pinnularia, P.hupingensissp. nov., on the basis of light and scanning electron microscope images. Pinnulariahupingensissp. nov. is characterised by its linear valve outline, extremely divergent striae, and very large hexagonal central area occupying ca. 1/5-1/8 of the valve length. The primary and secondary sides of the valve and the internal proximal raphe fissures are discussed. The new species is compared to similar taxa of the genus Pinnularia.

Single-atom tailored atomically-precise nanoclusters for enhanced electrochemical reduction of CO2-to-CO activity.

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

Relationship Between Change in Participation and Later Mental Health Problems in Children.

BACKGROUND: Participation in everyday activities is beneficial for mental health. However, little is known about the extent to which changes in children's participation are associated with later mental health. OBJECTIVES: To investigate the association between changes in the frequency and involvement in home, school, and community activities and subsequent mental health problems in children. Methodology: We recruited 242 school-aged children. Their parents completed the Participation and Environment Measure for Children and Youth twice, and after 2 years, they completed the Strengths and Difficulties Questionnaire. RESULTS: After controlling for demographic factors, hierarchical regression analysis revealed that reductions in children's involvement in home and community activities were significantly associated with elevated levels of externalizing and internalizing problems. Furthermore, an increase in children's involvement in school activities showed significant relationships with better mental health outcomes. CONCLUSION: These findings inform participation-based interventions for occupational therapists aimed at mitigating children's future mental health problems.

Participation in everyday activities is beneficial for mental health. However, little is known about the extent to which changes in children's participation are associated with later mental health. This study aimed to investigate the association between changes in the frequency and involvement in home, school, and community activities and subsequent mental health problems in children. We recruited 242 school-aged children. Their parents completed the Participation and Environment Measure for Children and Youth twice, and after 2 years, they completed the Strengths and Difficulties Questionnaire. After controlling for demographic characteristics, the analysis revealed that reductions in children's involvement in home and community activities were significantly associated with elevated levels of externalizing and internalizing problems. Furthermore, an increase in children's involvement in school activities showed significant relationships with better mental health outcomes. These findings inform participation-based interventions for occupational therapists aimed at mitigating children's future mental health problems.

Expert consensus on the workflow of digital aesthetic design in prosthodontics / 实用口腔医学杂志

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Slug-Flow Microextraction Mass Spectrometry for Enhanced Detection of Analytes in Human Tear Fluids using Noninvasive Microsampling and Nanoelectrospray Ionization via a Capillary.

In vivo noninvasive sampling and sensitive analysis of human tear fluids at the microliter level is an important but challenging task in investigating eye health. In this work, capillary microsampling coupled with slug-flow microextraction mass spectrometry (SFME-MS) was developed for enhanced detection of analytes in human tear fluids. As low as 1.0 µL of human tear fluid could be directly sampled using a capillary, and extraction/spray solvent was then loaded into the capillary to perform slug-flow microextraction and direct nanoelectrospray ionization (nESI) of analytes. All analytical procedures, including tear microsampling, microextraction, and ionization of analytes, were performed using a capillary. Enhanced detection of therapeutic drugs and disease biomarkers in human tear fluids was successfully demonstrated. Acceptable analytical performances including sensitivity, reproducibility, and quantitation were obtained. It is found that the use of SFME could improve the nESI-MS detection of trace analytes over 100-fold that depends on the chemical properties of analytes. Overall, this study showed that SFME-nESI-MS is a highly effective method for enhanced detection of trace analytes in tear fluids and is expected to be a potentially powerful tool in significant biological and clinical applications.

Altered neutrophil-to-lymphocyte ratio in patients with non-affective first episode psychosis and its relationship with symptom severity and cognitive impairment.

Signatures of immune dysregulation as clinical biomarker for psychosis have remained unclear. We aimed to compare the Neutrophil-to-lymphocyte ratio (NLR) of patients with acute non-affective first-episode psychosis (FEP) with healthy controls after accounting for emotional states. We also explored the associations of NLR with symptom severity, onset profile and cognitive functions. The NLR was enumerated from complete blood count taken within a week of assessment. All FEP patients were rated on the Positive and Negative Syndrome Scale (PANSS) and the Clinician Global Impression-Severity (CGI-S) with verbal memory and executive functions assessed with the Cambridge Neuropsychological Test Automated Battery. Prevailing emotional state was measured with Beck Depression Inventory-II and Beck Anxiety Inventory. Out of seventy-nine consecutive FEP patients presenting to the study site, twenty-seven subjects were eligible and recruited. Twenty-seven age-/sex-matched controls were recruited. FEP patients had an NLR of 1.886 over the controls after accounting for scores on emotional states. The NLR of FEP patients was positively associated with CGI-S scores, PANSS positive symptom, disorganization and excitation scores. There was no significant correlation between NLR with the duration of untreated psychosis and cognitive performances. These findings support using NLR as a clinical biomarker in FEP, purporting further prospective study to measure NLR changes in the course of treatment.

Portable Mass Spectrometry Approach Combined with Machine Learning for Onsite Field Detection of Huanglongbing Disease.

Huanglongbing (HLB) is one of the most serious citrus diseases in the world. Rapid, onsite, and accurate field detection of HLB is a challenging task in analytical science for a long time. Herein, we have developed a novel HLB detection method that combines headspace solid phase microextraction with portable gas chromatography-mass spectrometry (PGC-MS) approach for onsite field detection of volatile metabolites of citrus leaves. Detectability and characteristics of HLB-affected metabolites from leaves were validated, and the important biomarkers were verified by authentic compounds. A machine learning approach based on random forest algorithm is established to model the volatile metabolites from healthy, symptomatic, and asymptomatic citrus leaves. In this work, a total of 147 citrus leaf samples were analyzed. Analytical performances of this newly developed method were investigated by in-field detection of various volatile metabolites. Results demonstrated limits of detection and quantification of 0.04-0.12 and 0.17-0.44 ng/mL for different metabolites, respectively. Linear calibration curves of various metabolites were established over a concentration dynamic range of at least three orders (R2 > 0.96). Good reproducibility was obtained for intraday (3.0-17.5%, n = 6) and interday precision (8.7-18.2%, n = 7). This new HLB field detection method provides a rapid detection with 6 min for each sample via a simple optimized procedure, including onsite sampling, PGC-MS analysis, and data process and provides a high accuracy (93.3%) for simultaneous identification of healthy, symptomatic, and asymptomatic trees. These data support the use of this new method for reliable field detection of HLB. Furthermore, metabolic pathways of HLB-affected metabolites were also proposed. Overall, our results not only provide a rapid and onsite field HLB detection method but also provide valuable information for understanding metabolic change of HLB infection.

[Research Progress and New Immunotherapy Strategies of Tumor Microenvironment Metabolism].

The tumor microenvironment (TME), the environment of tumorigenesis and tumor progression, incorporates multiple types of cells and non-cellular components. TME plays an important role in tumorigenesis and tumor progression. Due to the abnormal proliferation of tumors, the TME has a unique chemophysiology environment and complex metabolic patterns, which subsequently affects the role of immune cells. Understanding the metabolic patterns of TME can help us develop immunotherapy regimens that target TME. Microbial metabolism and lipid metabolism, the key metabolic processes of TME, have emerged as important foci of research. The metabolites released by the microbiome and the reprogramming of cellular lipid metabolism affect the subsistence of tumor and immune cells. In this review, we summarized the composition and metabolic characteristics of TME and discussed the latest research progress in microbial metabolism and lipid metabolism in TME. We also provided an update on relevant metabolic regulatory targets and immunotherapy strategies, stressing that identifying highly effective therapeutic targets, in spite of the apparent difficulty, is what future research should be focused on.