Potential Clues Research Articles

Association between the neutrophil-to-high-density lipoprotein cholesterol ratio with kidney stone risk: a cross-sectional study

ObjectiveKidney stones are a major issue for public health worldwide. Discovering potential clues in identifying at-risk individuals is essential for early detection and timely treatment. This study explores the relationship of the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) with the risk of kidney stones in U.S. adults.MethodsThe analysis involved 24,532 participants with available NHR and kidney stone data from the 2007–2018 NHANES period. Multivariable logistic regression models were used to quantify the relationship between NHR and kidney stone occurrence. Subgroup analyses were conducted to explore variations in effect.ResultsA total of 2,351 participants (9.93%) were diagnosed with kidney stones, and their mean age was 47.20 ± 0.26 years. After full adjustment in the multivariable regression model, higher NHR levels were linked to a greater risk of kidney stones (OR = 1.05, 95% CI: 1.02–1.08, P = 0.002). Participants in the highest tertile of NHR had a 34% increased chance of kidney stone development compared to those in the lowest tertile. A nonlinear connection between NHR and kidney stone risk was identified using restricted cubic spline (RCS) regression models. The relationship between NHR and kidney stone prevalence showed no significant variation across most subgroups (P for interaction > 0.05).ConclusionThe results indicate that increased NHR is linked to a higher risk of kidney stones, with this relationship remaining consistent across various populations. NHR could be a useful biomarker for kidney stone risk, with key implications for early detection and individualized treatment.

Gastroprotective effect of fucoidan from Sargassum siliquastrum against ethanol-induced gastric mucosal injury.

The ethanol-induced BALB/c mice and human gastric epithelial cell (Ges-1 cell) models were used to investigate the Sargassum siliquastrum fucoidan (SFuc) gastroprotective capability. The injury score and histopathological sections of the stomach were used to evaluate the gastroprotective capability. The western blotting and RT-PCR methods determined the signaling mechanism of mice's gastric injury. SFuc is fucoidan with a molecular weight of 300.7 and 25.1kDa. The injury score and ulcer index of the SFuc-200 group decreased by 3.85 and 2.06 folds in contrast with the Model group, respectively. The findings indicated that SFuc reduced oxidative stress and inflammatory factor expression in the gastric mucosa by downregulating the levels of associated genes within the TLR-4, MyD88, and MAPK/NF-κB signaling pathways. Meanwhile, the SFuc-200 group promoted the expressions of EGF and PGE 2 by 1.53 and 1.52 folds, respectively. Together with the expression inhibition of p38, ERK, JNK, and NF-κB proteins in gastric tissue to help for differentiation of gastric cells. In addition, SFuc significantly reduced apoptosis occurrence in mice and Ges-1 cells. Our study provides potential mechanism clues of the SFuc's resistance to ethanol-induced gastric mucosal damage, suggesting its potential functional food for gastric protection.

Elucidating the Mechanisms of Acquired Palbociclib Resistance via Comprehensive Metabolomics Profiling.

Palbociclib is a cyclin-dependent kinase 4/6 inhibitor and a commonly used antitumor drug. Many cancers are susceptible to palbociclib resistance, however, the underlying metabolism mechanism and extent of resistance to palbociclib are unknown. In this study, LC-MS metabolomics was used to investigate the metabolite changes of colorectal cancer SW620 cells that were resistant to palbociclib. The study indicated that there were 76 metabolite expression differences between SW620 cells with palbociclib resistance and the parental SW620 cells involving amino acids, glutathione, ABC transporters, and so on. MetaboAnalyst 6.0 metabolic pathway analysis showed that arginine synthesis, β-alanine metabolism, and purine metabolism were disrupted. These results may provide potential clues to the metabolism mechanism of drug resistance in cancer cells that are resistant to palbociclib. Our study has the potential to contribute to the study of anti-palbociclib resistance.

Multi-omics analysis reveals genetic architecture and local adaptation of coumarins metabolites in Populus

BackgroundAccumulation of coumarins plays key roles in response to immune and abiotic stress in plants, but the genetic adaptation basis of controlling coumarins in perennial woody plants remain unclear.ResultsWe detected 792 SNPs within 334 genes that were significantly associated with the phenotypic variations of 15 single-metabolic traits and multiple comprehensive index, such as principal components (PCs) of coumarins metabolites. Expression quantitative trait locus mapping uncovered that 337 eQTLs associated with the expression levels of 132 associated genes. Selective sweep revealed 55 candidate genes have potential selective signature among three geographical populations, highlighting that the coumarins biosynthesis have been encountered forceful local adaptation. Furthermore, we constructed a genetic network of seven candidate genes that coordinately regulate coumarins biosynthesis, revealing the multiple regulatory patterns affecting coumarins accumulation in Populus tomentosa. Validation of candidate gene variations in a drought-tolerated population and DUF538 heterologous transformation experiments verified the function of candidate genes and their roles in adapting to the different geographical conditions in poplar.ConclusionsOur study uncovered the genetic regulation of the coumarins metabolic biosynthesis of Populus, and offered potential clues for drought-tolerance evaluation and regional improvement in woody plants.

Comprehensive genetic profile of Chinese muscle-invasive bladder cancer cohort

ObjectiveThe aim of our study was to characterize the spectrum of mutations in muscle-invasive bladder cancer (MIBC) in the Chinese population, identifying mutational features and exploring potential therapeutic targets. MethodsWe collected samples from 62 Chinese patients with MIBC. For each patient, tumor tissues or blood samples were collected and sequenced by whole exome sequencing. ResultsOur findings revealed the most frequently mutated genes included TP53 (41%), TTN (41%), HYDIN (34%), FRG1 (33%), ZNF717 (23%), AHNAK2 (21%), MUC4 (21%), KMT2D (20%), CDC27 (18%) and IGSF3 (18%). The most frequently mutated DNA damage repair (DDR) genes were TP53 (49%), SMARCA4 (10%), ERCC2 (8%), BRAC2 (6%), HERC2 (6%), HLTF (6%), PALB2 (6%) and POLG (6%). Additionally, our analysis confirmed an association between DDR mutations and high TMB (P = 0.022). Significant differences in MSI were observed between smokers and nonsmokers (P = 0.022), drinkers and nondrinkers (P = 0.018). By analyzing the data of 323 white MIBC samples from TCGA database, we identified frequently mutated driver genes in both our cohort and TCGA white cohort, including TP53, KMT2D, KMT2C, and FGFR3. Our study also revealed genes with distinct mutation frequencies compared to the TCGA white cohort, including FRG1, CDC27, IGSF3, MUC16, and ARID1A. ConclusionsOur study provided comprehensive insights into genomic alterations in a cohort of Chinese MIBC, which could provide potential clues for clinical applications. MicroAbstractThis study aimed to characterize mutations in muscle-invasive bladder cancer (MIBC) in the Chinese population, identifying mutational features and potential therapeutic targets. Samples from 62 Chinese MIBC patients were sequenced using whole exome sequencing, revealing frequent mutations in genes like TP53, TTN, and HYDIN. The study also found associations between DNA damage repair mutations and high tumor mutational burden, as well as differences in mutational profiles between Chinese and white MIBC cohorts. These findings offer valuable insights for clinical applications in Chinese MIBC patients.

Early detection of cervical tumor cell of origin through Oncogene-induced senescent HPV-positive cells.

Human Papilloma Virus (HPV) is an oncogenic virus and is the most common cause of cervical cancer. HPV has been shown to induce senescence. Cellular senescence is involved in cancer progression and tumorigenesis. Identification and isolation of cells of tumor origin before tumorigeneses is an important step in cancer prevention and treatment. This study aimed to investigate the early cervical atypical senescent cytological preneoplastic change in non-menopausal women. Cervical smears of 121 patients were randomly selected and included in the study which cytopathologically diagnosed as atypical squamous cells of undetermined significance (AS-CUS) in correlation to HPV status, parakeratosis (PK), p16 immunostaining, enlarged Squamous cells nuclei (ES) and inflammatory cells infiltration (ICI). Results revealed that out of the total 121 patients, 32 cases (26%) were positive for high-risk HPV (HR-HPV), 26 cases (22%) were positive for low-risk HPV (LR-HPV) and 63 (52%) were negative for HPV. HPV infections were significantly associated with age groups (p<0.026), PK (p = 0.043), p16 (p = 0.001), ES (p = 0.002) and ICI (p = 0.049). The positive immunostaining expression of p16 was only noticed in two HR-HPV patients. ES cells were found in 9.5% of HPV-negative cases, 27% of LR-HPV cases and 40.5% of HR-HPV cases. High PK cell positivity was seen only in HR-HPV. High ICI scores were seen in 40.6% of HR-HPV patients, 26.9 % of LR-HPV and 17.4 % of negative HPV patients. It was concluded that high PK positivity, high ICI score, positive p16 immunostaining and ES were correlated with HR-HPV in non-menopausal women. These findings could provide potential diagnostic clues for HPV-harboring senescent cells as a strategy for reducing HPV risk of cervical cancer development and identifying the cell of tumor origin, which could be beneficial for improving the utility of senolytic agents and immunotherapy in clinical practice.

Clinical insights into tuberculosis otitis media: diagnosis, treatment, and management outcomes.

The diagnosis of tuberculosis otitis media (TBOM) remains a great challenge. This study aims to suggest potential diagnostic clues and proper management of TBOM. The study is a retrospective review of TBOM cases that were treated at our department, between January 2015 and June 2023. Summarizing their clinical characteristics, diagnosis, and treatment. Additionally, a literature review is conducted. Eight cases of TBOM, 6 female and 2 male patients, median age was 32years old, were included in the study. TBOM mainly presents with symptoms of otorrhea, hearing loss, and occasional early-onset facial palsy. One case had a positive Purified Protein Derivative (PPD) before the operation. Middle ear tissue was pathologically biopsied in 7 cases, with 3 cases testing positive for Acid Fast Bacillus and 6 cases testing positive for Mycobacterium tuberculosis PCR. Middle ear surgery and Anti-tubercular treatment (ATT) were completed in all cases. The median follow-up was 11months. No cases of TB relapse were observed. Proper suspicion and confirmation of TBOM is the primary clinical orientation. Middle ear surgery combination with ATT results in satisfactory outcomes. Hearing reconstruction should be performed after ATT is completed.

Heterotrophic nitrification by Alcaligenes faecalis links organic and inorganic nitrogen metabolism.

Heterotrophic nitrification remains a mystery for decades. It has been commonly hypothesized that heterotrophic nitrifiers oxidize ammonia to hydroxylamine and then to nitrite in a way similar to autotrophic AOA and AOB. Recently, heterotrophic nitrifiers from Alcaligenes were found to oxidize ammonia to hydroxylamine and then to N2 ("dirammox", direct ammonia oxidation) by the gene cluster dnfABC with a yet-to-be-reported mechanism. The role of a potential glutamine amidotransferase DnfC clues the heterotrophic ammonia oxidation might involving in glutamine. Here, we found Alcaligenes faecalis JQ135 could oxidize amino acids besides ammonia. We discovered that glutamine is an intermediate of the dirammox pathway and the glutamine synthetase gene glnA is essential for both A. faecalis JQ135 and the Escherichia coli cells harboring dnfABC gene cluster to oxidize amino acids and ammonia. Our study expands understanding of heterotrophic nitrifiers and challenges the classical paradigm of heterotrophic nitrification.

Untargeted Metabolomic Analyses of Body Fluids to Differentiate TBI DOC and NTBI DOC.

To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.

Fetal weight growth trajectories and childhood development: A population-based cohort study

This study aimed to investigate whether fetal growth trajectories (FGTs) could predict early childhood development, indicate intrauterine metabolic changes, and explore potential optimal and suboptimal FGTs. FGTs were developed by using an unsupervised machine-learning approach. Children’s neurodevelopment, anthropometry, and respiratory outcomes in the first 6 years of life were assessed at different ages. In a subgroup of participants, we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs. We identified 6 FGTs: early decelerating, early decelerating with late catch-up growth, early accelerating, early accelerating with late medium growth, late decelerating, and late accelerating. The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development, mental development, intelligence quotient, and lung function and a lower risk of behaviour and respiratory problems. Compared with the optimal FGT, early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function, while early accelerating FGT was associated with more severe autistic symptoms, poor lung function, and increased risks of overweight/obesity. Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs, whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT. These findings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism. The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease, but further research on related mechanisms is still needed.

Genetic assessment of the causal effect of plasma metabolites and metabolic pathways on delirium

PurposeDelirium has a significant impact on millions of people globally and is closely linked to an unfavorable prognosis for complications. Observational studies suggest that plasma metabolites may play significant roles as markers and effectors of delirium, but causal relationships have not yet been elucidated. Based on the most recent genome-wide association study (GWAS) data, our study aims to present novel insights into the genetic relationship between delirium and plasma metabolites. This investigation offers potential clues for utilizing plasma metabolites as predictors of delirium development.MethodsWe performed a thorough Mendelian randomization (MR) analysis to investigate the causal relationship between 1,091 individual metabolites and 309 metabolite ratios in plasma with respect to delirium. Inverse-variance weighting (IVW) was employed as the primary estimation method, while MR-Egger and weighed median methods were utilized to assess the robustness of the results. Sensitivity analyses encompassing the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, Cochran Q test, leave-one-out analysis and MR Egger intercept analysis were also undertaken. Additionally, the MR Steiger test was performed to explore any potential reverse causal effect of metabolites on delirium.ResultsA total of 63 types of plasma metabolites associated with delirium were detected using the IVW method (p < 0.05). Among the known metabolites, our analysis revealed that two specific metabolites (1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and homovanillate) and a metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) demonstrated a consistent and significant causal relationship with delirium across all analysis methods. Finally, no evidence of pleiotropy was detected in our analysis.ConclusionsOur study has revealed a causal association between blood metabolites and the risk of delirium. homovanillate is known to be associated with immunity and redox, 1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) may play a role in lipid regulation. These findings may provide fresh insights into the identification of suitable diagnostic markers and potential treatment strategies focused on specific plasma metabolites in patients with delirium. However, further experiments are required to gain a comprehensive understanding of the underlying biological mechanisms involved.

A multiplexed high throughput screening assay using flow cytometry identifies glycolytic molecular probes in bloodstream form Trypanosoma brucei

Kinetoplastid organisms, including Trypanosoma brucei, are a significant health burden in many tropical and semitropical countries. Much of their metabolism is poorly understood. To better study kinetoplastid metabolism, chemical probes that inhibit kinetoplastid enzymes are needed. To discover chemical probes, we have developed a high-throughput flow cytometry screening assay that simultaneously measures multiple glycolysis-relevant metabolites in live T. brucei bloodstream form parasites. We transfected parasites with biosensors that measure glucose, ATP, or glycosomal pH. The glucose and ATP sensors were FRET biosensors, while the pH sensor was a GFP-based biosensor. The pH sensor exhibited a different fluorescent profile from the FRET sensors, allowing us to simultaneously measure pH and either glucose or ATP. Cell viability was measured in tandem with the biosensors using thiazole red. We pooled sensor cell lines, loaded them onto plates containing a compound library, and then analyzed them by flow cytometry. The library was analyzed twice, once with the pooled pH and glucose sensor cell lines and once with the pH and ATP sensor cell lines. Multiplexing sensors provided some internal validation of active compounds and gave potential clues for each compound's target(s). We demonstrated this using the glycolytic inhibitor 2-deoxyglucose and the alternative oxidase inhibitor salicylhydroxamic acid. Individual biosensor-based assays exhibited a Z′-factor value acceptable for high-throughput screening, including when multiplexed. We tested assay performance in a pilot screen of 14,976 compounds from the Life Chemicals Compound Library. We obtained hit rates from 0.2 to 0.4% depending on the biosensor, with many compounds impacting multiple sensors. We rescreened 44 hits, and 28 (64%) showed repeatable activity for one or more sensors. One compound exhibited EC50 values in the low micromolar range against two sensors. We expect this method will enable the discovery of glycolytic chemical probes to improve metabolic studies in kinetoplastid parasites.

What are the frequent complaints voiced by inpatients and physicians amidst the emerging infectious diseases? — An illustrative instance of the COVID-19

IntroductionEmerging infectious diseases (EIDs) can disrupt the healthcare system, causing regulatory changes that affect the healthcare-seeking process and potentially increase patient-physician dissatisfaction. This study aimed to collect and analyze patients’ and physicians’ complaints during an EID outbreak to inform potential clues regarding medical quality and patient safety enhancement in future dealing with EIDs, employing text mining methodologies.MethodsIn this descriptive study, complaint records from January 2020 to February 2023 at West China Hospital, a national medical facility in China, were analyzed. Patient and physician complaints have been retrospectively retrieved from the record from the medical department, and then categorized into distinct groups based on reporting reasons, encompassing COVID-19-related policies, healthcare access, availability of medical resources, and financial concerns.ResultsDuring the COVID-19 pandemic, 541 COVID-19-related complaints were identified: 330 (61.00%) from patients and 211 (39.00%) from physicians. The monthly volume of complaints fluctuated, starting at 10 in 2020, peaking at 21 in 2022, and dropping to 14 in 2023. Most complaints from inpatients were expressed by older males aged 40 to 65 (38.82%, 210/541). The primary source of complaints was related to mandatory COVID-19 policies (79.30%, 429/541), followed by concerns regarding timely healthcare services (31.61%, 171/541). Few complaints were expressed regarding the insufficiency of medical resources (2.77%, 15/541) and the high costs (4.25%, 23/541). The frequency of complaints expressed by doctors and patients in the emergency department was higher compared with other departments (24.58%, 133/541).ConclusionsIncreased complaints may serve as a primitive and timely resource for investigating the potential hazards and drawbacks associated with policies pertaining to EIDs. Prompt collection and systematical analysis of patient and physician feedback could help us accurately evaluate the efficacy and repercussions of these policies. Implementing complaints-based assessment might improve care standards in forthcoming healthcare environments grappling with EIDs.

AI-ASSISTED MISSING PERSON FINDER AND FACE RECOGNITION USING FACENET ALGORITHM

Thephenomenon of missing persons poses a significant societal challenge, requiring efficient and effective search and rescue operations. Recently, the blending of artificial intelligence and machine learning methods has demonstrated potential to considerably improve the process of finding missing persons. This paper presents an AI-assisted missing person finder system that harnesses the power of ML algorithms to augment traditional search methodologies. By drawing from an array of information pools such as surveillance video, social networking activity, and geographic specifics, the suggested framework aims to assemble complete individual profiles and potential clues for locating disappeared individuals. By leveraging cutting-edge machine learning techniques including deep neural networks, pattern identification, and natural language decoding, the platform has the capability to intensively examine huge volumes of diverse information and uncover meaningful patterns within the data that could provide clues concerning a missing individual's location or activities. Furthermore, through incorporating algorithmic techniques that optimize search strategies, prioritize promising leads, and coordinate search efforts in real time, the system is able to dynamically adjust its approach. Here is the rewritten sentence using a more complex structure while maintaining the same concepts: By outlining its design, implementation, and evaluation process, this paper aims to highlight how the AI-assisted missing person finder has the potential to dramatically boost both the efficiency and effectiveness of search and rescue operations through leveraging the latest advances in artificial intelligence. Furthermore, it addresses ethical considerations, privacy concerns, and future research directions in the development and deployment of AI-powered solutions for locating missing individuals.

Genomic analysis of an outbreak of Shiga toxin-producing Escherichia coli O183:H18 in the United Kingdom, 2023.

In June 2023, UKHSA surveillance systems detected an outbreak of severe gastrointestinal symptoms caused by a rare serotype of Shiga toxin-producing Escherichia coli, STEC O183:H18. There were 26 cases aged 6 months to 74 years (42 % cases were aged 0-9 years), distributed across the UK with onset dates range between 22 May 2023 and 4 July 2023. The epidemiological and food chain investigations were inconclusive, although meat products made from beef mince were implicated as a potential vehicle. The outbreak strain belonged to sequence type (ST) 657 and harboured a Shiga toxin (stx) subtype stx2a located on a prophage that was unique in the UKHSA stx-encoding bacteriophage database. Plasmid encoded, putative virulence genes subA, ehxA, saa, iha, lpfA and iss were detected, however, the established STEC virulence genes involved in attachment to the gut mucosa (eae and aggR) were absent. The acquisition of stx across the global population structure of ST657 appeared to correspond with the presence of subA, ehxA, saa, iha, lpfA and iss. During the outbreak investigation, we used long read sequencing to characterise the plasmid and prophage content of this atypical STEC, to look for evidence to explain its recent emergence. Although we were unable to determine source and transmission route of the outbreak strain, the genomic analysis revealed potential clues as to how novel strains for STEC evolve. With the implementation of PCR capable of detecting all STEC, and genome sequencing for typing and virulence profiling, we have the tools to enable us to monitor the changing landscape of STEC. Improvements in the standardised collection of epidemiological data and trace-back strategies within the food industry, will ensure we have a surveillance system capable of alerting us to emerging threats to public health.

A practical, step-by-step, guide to taxonomic comparisons using Procrustes geometric morphometrics and user-friendly software (part B): group comparisons

In this second part of the study, using a ‘clean’ dataset without very low precision landmarks and outliers, I describe how to compare mandibular size and shape using Procrustes methods in adult North American marmots. After demonstrating that sex differences are negligible, females and males are pooled together with specimens of unknown sex and species are compared using a battery of tests, that estimate both statistical significance and effect size. The importance of allometric variation and its potential effect on shape differences is also explored. Finally, to provide potential clues on founder effects, I compare the magnitude of variance in mandibular size and shape between the Vancouver Island marmot (VAN) and the hoary marmot, its sister species on the mainland. In almost all main analyses, I explore the sensitivity of results to heterogeneous sample size and small samples using subsamples and randomized selection experiments. For both size and shape, I find a degree of overlap among species variation but, with very few exceptions, mean interspecific differences are well supported in all analyses. Shape, in particular, is an accurate predictor of taxonomic affiliation. Allometry in adults, however, explains a modest amount of within-species shape change. Yet, there is a degree of divergence in allometric trajectories that seems consistent with subgeneric separation. VAN is the most distinctive species for mandibular shape and mandibular morphology suggests a long history of reduced variation in this insular population. Geometric morphometrics (GMM) is a powerful tool to aid taxonomic research. Regardless of the effectiveness of this family of methods and the apparent robustness of results obtained with GMM, however, large samples and careful measurements remain essential for accuracy. Even with excellent data, morphometrics is important, but its findings must be corroborated with an integrative approach that combines multiple lines of evidence to taxonomic assessment. The analytical protocol I suggest is described in detail, with a summary checklist, in the Appendix, not to miss important steps. All the analyses can be replicated using the entire dataset, which is freely available online. Beginners may follow all the steps, whereas more experienced researchers can focus on one specific aspect and read only the relevant chapter. There are limitations, but the protocol is flexible and easy to improve or implement using a programming language such as R.

Differential fluorescence features and recovery speeds of different scorpion exoskeleton parts during the molting process

Scorpion fluorescence under ultraviolet light is a well-known phenomenon, but its features under excitation in the UVA, UVB and UVC bands have not been characterized. Systematic fluorescence characterization revealed indistinguishable fluorescence spectra with a peak wavelength of 475 nm for whole exuviae from second-, third- and fifth-instar scorpions under different ultraviolet light ranges. In-depth investigations of the chelae, mesosoma, metasoma and telson of adult scorpions further indicated heterogeneity in the typical fluorescence spectrum within the visible light range and in the newly reported fluorescence spectrum with a peak wavelength of 320 nm within the ultraviolet light range, which both showed excitation wavelength-independent features. Dynamic fluorescence changes during the molting process of third-instar scorpions revealed the fluorescence heterogeneity-dependent recovery speed of scorpion exoskeletons. The typical fluorescence spectra of the molted chelae and telson rapidly recovered approximately 6 h after ecdysis under UVA light and approximately 36 h after ecdysis under UVB and UVC light. However, it took approximately 12 h and 24 h to obtain the typical fluorescence spectra of the molted metasoma and mesosoma, respectively, under UVA irradiation and 72 h to obtain the typical fluorescence spectra under UVB and UVC irradiation. The fluorescence heterogeneity-dependent fluorescence recovery of the scorpion exoskeleton was further confirmed by tissue section analysis of different segments from molting third-instar scorpions. These findings reveal novel scorpion fluorescence features and provide potential clues on the biological function of scorpion fluorescence.

Recurrent (or episodic) fever of unknown origin (FUO) as a variant subgroup of classical FUO: A French multicentre retrospective study of 170 patients

BackgroundRecurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking. MethodsWe performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality. ResultsOf 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death. ConclusionThis study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent.

Metabolite profiling of potential bioactive fractions from ethanol extract of Boehmeria nivea flowers by GC–MS/MS analysis

BackgroundRamie (Boehmeria nivea) has been reported to have a wide variety of secondary metabolite compounds in its vegetative organ that have distinct organic activities. Regarding the chemical composition of flowers, there have been no study considering their pharmacological effects. PurposeThis research aims to determine profile metabolites contained in B. nivea flowers employing a metabolomics approach. Study DesignThis research was designed to obtain a metabolite database from five dissolved fractions of ramie flower using a Gas Chromatography-Mass Spectrometry (GC–MS/MS) instrument. This study includes metabolite profiles from each fraction of the spectrum obtained, which are then investigated for potential bioactivity based on previously reported studies. Metabolite profiles were developed using Principal Component Analysis (PCA) to obtain information on clustering of the compounds and determination of marker compounds from each fraction analyzed. MethodsThe active compounds of the flowers were separated utilizing the maceration method with ethanol solvent and multilevel fractionation using n-hexane, dichloromethane, ethyl acetic acid derivation, butanol, and water employing a GC–MS/MS approach. Principal Component Analysis (PCA) was optimized with a total represented data diversity range of 60 % - 65 %. This allowed for the identification of characteristic compounds and similarities in compound substances accross the fractions. ResultGC–MS/MS interpretation showed the dominant compounds contained in each fraction of n-hexane, dichloromethane, n-butanol, ethyl acetate, and water are 9,12-Octadecadienoic acid, ethanol, 2-phenoxy-, butyl ester, and hexanedioic acid, bis(2-ethylhexyl) ester. PCA clustering showed combined similarity of the compound for ethyl acetate fraction with butanol, and also butanol with n-hexane. Meanwhile, the dichloromethane and water fractions have very small content similarities. The score plot indicated marker compounds of each fraction are: ethanol, 2-butoxy; hexane, 2,2,3-trimethyl-; phthalic acid, in (2-propylpentyl) ester; n-hexadecanoic acid, and Hexanedioic acid, bis(2- ethylhexyl) ester. ConclusionsThe abundance of compounds in the fractions shows potential for application as a source of new drug candidates. In addition, there are still many compounds that are unknown in structures or biological activities which could lead to further research to provide potential clues towards the bioprospecting of the plant. AbbreviationsCH2Cl2, dichloromethane; Dm1, Dimension 1; Dm2, Dimension 2; EtOAc, ethyl acetate; GC–MS/MS, Gas Chromatography–Mass Spectrometry; n-BuOH, n-butanol; PCA, Principal Component Analysis.

Hydrogen Sulfide in the Oxidative Stress Response of Plants: Crosstalk with Reactive Oxygen Species.

Growing evidence suggests that exposure of plants to unfavorable environments leads to the accumulation of hydrogen sulfide (H2S) and reactive oxygen species (ROS). H2S interacts with the ROS-mediated oxidative stress response network at multiple levels. Therefore, it is essential to elucidate the mechanisms by which H2S and ROS interact. The molecular mechanism of action by H2S relies on the post-translational modification of the cysteine sulfur group (-SH), known as persulfidation. H2S cannot react directly with -SH, but it can react with oxidized cysteine residues, and this oxidation process is induced by H2O2. Evidently, ROS is involved in the signaling pathway of H2S and plays a significant role. In this review, we summarize the role of H2S-mediated post-translational modification mechanisms in oxidative stress responses. Moreover, the mechanism of interaction between H2S and ROS in the regulation of redox reactions is focused upon, and the positive cooperative role of H2S and ROS is elucidated. Subsequently, based on the existing evidence and clues, we propose some potential problems and new clues to be explored, which are crucial for the development of the crosstalk mechanism of H2S and ROS in plants.