Estimating effects of whole grain consumption on type 2 diabetes, colorectal cancer and cardiovascular disease: a burden of proof study.

BACKGROUND: Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). METHODS: We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. RESULTS: In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5-148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). CONCLUSION: Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.

Different correlation between depressive symptoms and sleep duration on weekdays/weekends among adolescents in Taiyuan, North China.

OBJECTIVE: In Chinese adolescents, the co-occurrence of depressive symptoms and short sleep duration constitute a serious public health issue. This study investigates the association between depressive symptoms and sleep duration of Chinese adolescents on weekdays as well as weekends. METHODS: A multistage random cluster selection was utilized to select 2660 adolescents in Taiyuan, China. The survey contents included demographic characteristics, sleep duration, and depressive symptoms. RESULTS: About 41.95 % of students reported depressive symptoms with an average sleep duration of 7.71 ± 0.90 h. After adjusting for covariates, depressive symptoms were found to be positively correlated with sleep duration <6 h (OR = 1.88, 95 % CI: 1.20, 2.95) and 6 ~ h (OR = 1.61, 95 % CI: 1.18, 2.20) on weekdays, and sleep duration <6 h (OR = 2.10, 95 % CI: 1.17, 3.79) and 6 ~ hours (OR = 1.74, 95 % CI: 1.16, 2.62) on weekends compared with a sleep duration of 8 ~ hours. Only on weekdays, sleep duration of 7 ~ hours was positively correlated with depressive symptoms (OR = 1.39, 95%CI: 1.05, 1.84). On weekends, it was not associated with depressive symptoms (OR = 1.06, 95%CI: 0.82, 1.39). In subgroup analyses, female students (OR = 2.88, 1.97, 1.50) and middle school students (OR = 3.50, 2.07, 1.50) were more likely to experience depressive symptoms on weekdays with a sleep duration of <6 h, 6 ~ hours and 7 ~ hours. LIMITATIONS: Sleep duration and depressive symptoms were self-reported measures. CONCLUSION: The study highlights that short sleep duration (< 7 h) increases the risk of depressive symptoms among adolescents regardless of weekdays or weekends. Just on weekdays, the sleep duration of 7 ~ hours was a risk factor for depressive symptoms. Further, gender, grade, and the only-child played significant modification effects between depressive symptoms and sleep duration. To conclude, this study will assist in the effective promotion of the education of adolescents' sleep health.

Pangenome analyses of Clostridium butyricum provide insights into its genetic characteristics and industrial application.

Clostridium butyricum is a Gram-positive anaerobic bacterium known for its ability to produce butyate. In this study, we conducted whole-genome sequencing and assembly of 14C. butyricum industrial strains collected from various parts of China. We performed a pan-genome comparative analysis of the 14 assembled strains and 139 strains downloaded from NCBI. We found that the genes related to critical industrial production pathways were primarily present in the core and soft-core gene categories. The phylogenetic analysis revealed that strains from the same clade of the phylogenetic tree possessed similar antibiotic resistance and virulence factors, with most of these genes present in the shell and cloud gene categories. Finally, we predicted the genes producing bacteriocins and botulinum toxins as well as CRISPR systems responsible for host defense. In conclusion, our research provides a desirable pan-genome database for the industrial production, food application, and genetic research of C. butyricum.

Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma.

BACKGROUND: Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, and prognosis. There is still no research on the relationship between PCD-related genes and UVM. A novel PCD-associated prognostic model is urgently needed to improve treatment strategies. OBJECTIVE: We aim to screen PCD-related prognostic signature and investigate its proliferation ability and apoptosis in UVM cells. METHODS: The clinical information and RNA-seq data of the UVM patients were collected from the TCGA cohort. All the patients were classified using consensus clustering by the selected PCD-related genes. After univariate Cox regression and PPI network analysis, the prognostic PCD-related genes were then submitted to the LASSO regression analysis to build a prognostic model. The level of immune infiltration of 8-PCD signature in high- and low-risk patients was analyzed using xCell. The prediction on chemotherapy and immunotherapy response in UVM patients was assessed by GDSC and TIDE algorithm. CCK-8, western blot and Annexin V-FITC/PI staining were used to explore the roles of HMOX1 in UVM cells. RESULTS: A total of 8-PCD signature was constructed and the risk score of the PCD signature was negatively correlated with the overall survival, indicating strong predictive ability and independent prognostic value. The risk score was positively correlated with CD8 Tcm, CD8 Tem and Th2 cells. Immune cells in high-risk group had poorer overall survival. The drug sensitivity demonstrated that cisplatin might impact the progression of UVM and better immunotherapy responsiveness in the high-risk group. Finally, Overespression HMOX1 (OE-HMOX1) decreased the cell viability and induced apoptosis in UVM cells. Recuse experiment results showed that ferrostatin-1 (fer-1) protected MP65 cells from apoptosis and necrosis caused by OE-HMOX1. CONCLUSION: The PCD signature may have a significant role in the tumor microenvironment, clinicopathological characteristics, prognosis and drug sensitivity. More importantly, HMOX1 depletion greatly induced tumor cell growth and inhibited cell apoptosis and fer-1 protected UVM cells from apoptosis and necrosis induced by OE-HMOX1. This work provides a foundation for effective therapeutic strategy in tumour treatment.

Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation.

The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.

Development and Immunological Evaluation of a Multiantigen Thermostable Nanovaccine Adjuvanted with T-Cell-Activating Scaffold for African Swine Fever.

African swine fever is an acute and highly contagious infectious disease with a mortality rate of up to 100%. The lack of commercial vaccines and drugs is a serious economic threat to the global pig industry. Cell-mediated immunity plays an essential role in protection against viral infection. We previously reported the rational design of a T-cell-activating thermostable scaffold (RPT) for antigen delivery and improved cellular immunity. We conjugated antigens P30, P54, P72, CD2 V, and CP312R to RPT, using a SpyCatcher/SpyTag covalent attachment strategy to construct nanovaccines (multiantigens-RPT). Multiantigens-RPT exhibited significantly higher thermal, storage, and freeze-thaw stability. The specific antibodies IgG and IgG2a of the multiantigen-RPT-immunized were higher than the antigens cocktail-immunized by approximately 10-100 times. ELISpot demonstrated that more IFN-γ-secreting cells were produced by the multiantigen-RPT-immunized than by the antigens cocktail-immunized. Delivery of the multiantigen nanovaccine by a T-cell-activating scaffold induced strong humoral and cellular immune responses in mice and pigs and is a potentially useful candidate vaccine for the African swine fever virus.

Understanding the educational inequalities in suicide attempts and their mediators: a Mendelian randomisation study.

Background: Educational inequalities in suicide have become increasingly prominent over the past decade. Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities. Aims: To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect. Methods: We conducted a two-sample Mendelian randomisation (MR) analysis to estimate the causal effect of educational attainment on suicide attempts, utilising genome-wide association study summary statistics from the Integrative Psychiatric Research (iPSYCH; 6024 cases and 44 240 controls) and FinnGen (8978 cases and 368 299 controls). We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect. Results: In the combined analysis of iPSYCH and FinnGen, each standard deviation (SD) decrease in genetically predicted educational attainment (equating to 3.4 years of education) was associated with a 105% higher risk of suicide attempts (odds ratio (OR): 2.05; 95% confidence interval (CI): 1.81 to 2.31). Of the 42 risk factors analysed, the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts. The respective proportions of mediation were 47% (95% CI: 29% to 66%) for smoking behaviour, 36% (95% CI: 0% to 84%) for chronic pain, 49% (95% CI: 36% to 61%) for depression, 35% (95% CI: 12% to 59%) for anxiety and 26% (95% CI: 18% to 34%) for insomnia. Multivariable MR implicated these five mediators collectively, accounting for 68% (95% CI: 40% to 96%) of the total effect. Conclusions: This study identified smoking, chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.

Mesophilic Argonaute-Mediated Polydisperse Droplet Biosensor for Amplification-Free, One-Pot, and Multiplexed Nucleic Acid Detection Using Deep Learning.

Detection of nucleic acids from a single multiplexed and amplification-free test is critical for ensuring food safety, clinical diagnostics, and environmental monitoring. In this study, we introduced a mesophilic Argonaute protein from Clostridium butyricum (CbAgo), which exhibits nucleic acid endonuclease activity, to achieve a programmable, amplification-free system (PASS) for rapid nucleic acid quantification at ambient temperatures in one pot. By using CbAgo-mediated binding with specific guide DNA (gDNA) and subsequent targeted cleavage of wild-type target DNAs complementary to gDNA, PASS can detect multiple foodborne pathogen DNA (<102 CFU/mL) simultaneously. The fluorescence signals were then transferred to polydisperse emulsions and analyzed by using deep learning. This simplifies the process and increases the suitability of polydisperse emulsions compared to traditional digital PCR, which requires homogeneous droplets for accurate detection. We believe that PASS has the potential to become a next-generation point-of-care digital nucleic acid detection method.

Neurogenic dry eye associated with intravitreal injection of anti-VEGF agents.

PURPOSE: To report a case of neurogenic dry eye (NDE) that developed after intravitreal ranibizumab injection (IVR). CASE REPORT: A 71-year-old woman had a history of cataract phacoemulsification and intraocular lens (IOL) implantation, Nd:YAG laser posterior capsulotomy and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Aneurysmal dilatation of the inferior temporal retina was found in the left fundus, which was diagnosed as retinal aneurysm, and intravitreal ranibizumab injection was administered. Dry eye was found in the left eye after the first injection. After the second injection, the patient developed severe dry eye with left eye dryness, photophobia, irritation, and blurred vision. The tear film breakup time (TBUT) value was 3 s, the Schirmer test value was 2 mm/5 min, corneal fluorescein staining (CFS) showed diffuse patellar staining of the corneal epithelium with a staining area of >50% and irregular staining at the edge of the corneal flap, and the corneal touch threshold value in the filament length was 1.5 cm in the left eye. CONCLUSIONS: Patients with a history of intraocular lens implantation, Nd:YAG laser posterior capsulotomy, and femtosecond laser-assisted laser in situ keratomileusis surgery may have increased drug permeability due to an increased concentration of anti-VEGF drugs in the aqueous layer and thinning of the stromal layer of the cornea. The corneal subepithelial nerve repair mechanism was destroyed, causing neurogenic dry eye.

Appraising the causal role of smoking in idiopathic pulmonary fibrosis: a Mendelian randomization study.

Smoking has been considered a risk factor for idiopathic pulmonary fibrosis (IPF) in observational studies. To assess whether smoking plays a causal role in IPF, we performed a Mendelian randomization study using genetic association data of 10 382 cases with IPF and 968 080 controls. We found that genetic predisposition to smoking initiation (based on 378 variants) and lifetime smoking (based on 126 variants) were associated with a higher risk of IPF. Our study suggests a potential causal effect of smoking on increasing IPF risk from a genetic perspective.

Mesophilic Argonaute-Based Single Polystyrene Sphere Aptamer Fluorescence Platform for the Multiplexed and Ultrasensitive Detection of Non-Nucleic Acid Targets.

The rapid, simultaneous, and accurate identification of multiple non-nucleic acid targets in clinical or food samples at room temperature is essential for public health. Argonautes (Agos) are guided, programmable, target-activated, next-generation nucleic acid endonucleases that could realize one-pot and multiplexed detection using a single enzyme, which cannot be achieved with CRISPR/Cas. However, currently reported thermophilic Ago-based multi-detection sensors are mainly employed in the detection of nucleic acids. Herein, this work proposes a Mesophilic Argonaute Report-based single millimeter Polystyrene Sphere (MARPS) multiplex detection platform for the simultaneous analysis of non-nucleic acid targets. The aptamer is utilized as the recognition element, and a single millimeter-sized polystyrene sphere (PSmm ) with a large concentration of guide DNA on the surface served as the microreactor. These are combined with precise Clostridium butyricum Ago (CbAgo) cleavage and exonuclease I (Exo I) signal amplification to achieve the efficient and sensitive recognition of non-nucleic acid targets, such as mycotoxins (<60 pg mL-1 ) and pathogenic bacteria (<102 cfu mL-1 ). The novel MARPS platform is the first to use mesophilic Agos for the multiplex detection of non-nucleic acid targets, overcoming the limitations of CRISPR/Cas in this regard and representing a major advancement in non-nucleic acid target detection using a gene-editing-based system.

Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study.

The association between osteoarthritis (OA) and gastrointestinal disorders was found in observational studies. However, the causality is still elusive. A bidirectional Mendelian randomization (MR) analysis using genome wide association studies data was conducted to assess the causal association between OA and gastrointestinal diseases [including peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), and inflammatory bowel disease (IBD)]. A two-step MR (TSMR) was conducted between OA, gastrointestinal diseases and drugs to explore the mediating effects of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids use. We used multivariable MR (MVMR) analysis to further validate the impact of prescription history on diseases. Results had statistical significance at a Bonferroni corrected P-value below 0.008. We observed that genetically predicted OA had a significant positive association with GORD [odds ratio (OR) = 1.26, P = 5e-05], but not with PUD or IBD. Regarding the other direction, gastrointestinal disorders as exposure had a null association with OA. Using TSMR, OA patients tended to increase the use of NSAIDs (OR = 1.45, P = 0.001) and opioids (OR = 1.77, P = 2e-05), but only the use of opioids increased the risk of GORD (OR = 1.43, P = 5e-09). Further MVMR analysis showed that the adverse effect of OA on GORD was significantly reduced after adjusting for opioids use (OR = 1.20, P = 0.038). This study provides evidence for the causal association between OA and increased risk of GORD, which is partly attributed to opioids use in OA patients but not NSAIDs.

Environmental concentrations of cadmium and zinc and associating metabolomics profile alternations in urine of pregnant women in the first trimester: A prospective cohort study in Taiyuan, North China.

especially to pregnant women. In recent years, zinc (Zn) supplementation has attracted increasing attention among pregnant women. Thus, understanding the effects and interactions of Cd and Zn in pregnant women is critical. This study aimed to assess the urinary levels of Cd and Zn in pregnant women during early pregnancy, examine associated alterations in urine metabolomics, and identify potential metabolic biomarkers among distinct Cd and Zn groups. Urine samples from 185 pregnant women were collected, and inductively coupled plasma mass spectrometry (ICP-MS) was used to detect Cd and Zn contents. The women were then divided into four groups according to median contents of Cd and Zn. Alterations in the metabolite profile were assessed using a liquid chromatograph mass spectrometer (LC-MS). The results showed that the gravidity of pregnant women was closely related to urinary Cd levels and that the urinary Zn contents of pregnant women with morning sickness in the first trimester were lower than that of non-morning-sick pregnant women. A total of 51 metabolites exhibited significant differential expression in the high level of Cd and Zn (HCdHZn) compared with low level of Cd and Zn (LCdLZn), the diagnostic performance of these 51 metabolites were assessed using receiver operating characteristic curve analysis and revealed that octadecylamine was a promising diagnostic indicator for evaluating the combined effects of Zn and Cd. Metabolomics analysis showed that the arginine and proline pathways were upregulated in HCdHZn compared with that in LCdLZn, suggesting a potential risk of obesity. Although higer levels of bovinic acid in HCdHZn vs. HCdLZn (high level of Cd and low level of Zn) indicated that Zn has antioxidant and anti-inflammatory properties, excessive Zn may still cause harmful effect to the human health and should be supplemented with caution. The study findings may be valuable for potential risk ahissessment of the combined effects of Cd-Zn and their interactions in pregnant women.

Systemic evaluation of the relationship between asthma and osteoarthritis: Evidence from a meta-analysis and Mendelian randomization study.

Objective: Osteoarthritis (OA) and asthma are two common chronic diseases with increasing incidence and prevalence, whereas there has been rare evidence to suggest the relationship between OA and asthma. This study aimed to analyze the causal relationship between OA and asthma. Methods: Existing studies of the relationship between asthma and OA published till July 18, 2023, were identified from PubMed and Web of Science databases for meta-analysis. Subsequently, the causal relationship of all and site-specific OA with asthma was explored through a bidirectional two-sample Mendelian randomization (MR) analysis. Results: A total of four eligible studies were included in the meta-analysis. In these studies, 80,550 participants were recruited, of whom 13,781 patients had OA. The asthma group had a significantly higher prevalence of OA than the control group (odds ratio (OR) = 2.08; 95% confidence intervals (CI): 1.42-3.03). However, MR analysis did not support a causal relationship between asthma and all OA and site-specific OA: knee and hip OA (OR = 1.03; 95% CI: 0.98-1.09), knee OA (OR = 1.02; 95% CI:0.96-1.08), and hip OA (OR = 1.04; 95% CI: 0.97-1.12). No causal relationship between OA and asthma was found through reverse MR analysis. Conclusions: This meta-analysis suggests that patients with asthma are likely to have a greater prevalence of OA. However, the result of MR analysis reveals that asthma does not have a causal relationship to all OA or site-specific OA.

Digital Pupillometry and Centroid Shift Changes in Dominant and Nondominant Eyes.

PURPOSE: To investigate the differences between dominant and nondominant eyes in a predominantly young patient population by analyzing the angle kappa, pupil size, and center position in dominant and nondominant eyes. METHODS: A total of 126 young college students (252 eyes) with myopia who underwent femtosecond laser-combined LASIK were randomly selected. Ocular dominance was determined using the hole-in-card test. The WaveLight Allegro Topolyzer (WaveLight Laser Technologies AG, Erlangen, Germany) was used to measure the pupil size and center position. The offset between the pupil center and the coaxially sighted corneal light reflex (P-Dist) of the patients was recorded by the x- and y-axis eyeball tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system (Wavelight GmbH). The patient's vision (uncorrected distance visual acuity [UDVA], best-corrected visual acuity (BCVA), and refractive power (spherical equivalent, SE) were observed preoperatively, 1 week, 4 weeks, and 12 weeks postoperatively, and a quality of vision (QoV) questionnaire was completed. RESULTS: Ocular dominance occurred predominantly in the right eye [right vs. left: (178) 70.63% vs. (74) 29.37%; p < 0.001]. The P-Dist was 0.202 ± 0.095 mm in the dominant eye and 0.215 ± 0.103 mm in the nondominant eye (p = 0.021). The horizontal pupil shift was - 0.07 ± 0.14 mm in dominant eyes and 0.01 ± 0.13 mm in nondominant eyes (p = 0.001) (the temporal displacement of the dominant eye under mesopic conditions). The SE was negatively correlated with the P-Dist (r = - 0.223, p = 0.012 for the dominant eye and r = - 0.199, p = 0.025 for the nondominant eye). At 12 weeks postoperatively, the safety index (postoperative BDVA/preoperative BDVA) of the dominant and nondominant eyes was 1.20 (1.00, 1.22) and 1.20 (1.00, 1.20), respectively, and the efficacy index (postoperative UDVA/preoperative BDVA) was 1.00 (1.00, 1.20) and 1.00 (1.00, 1.20), respectively; the proportion of residual SE within ± 0.50 D was 98 and 100%, respectively. CONCLUSIONS: This study found that ocular dominance occurred predominantly in the right eye. The pupil size change was larger in the dominant eye. The angle kappa of the dominant eye was smaller than that of the nondominant eye and the pupil center of the dominant eye was slightly shifted to the temporal side under mesopic conditions. The correction of myopia in the dominant and nondominant eyes exhibits good safety, efficacy, and predictability in the short term after surgery, and has good subjective visual quality performance after correction. We suggest adjusting the angle kappa percentage in the dominant eye to be lower than that of the nondominant eye in individualized corneal refractive surgery in order to find the ablation center closest to the visual axis.

Assessment of the bidirectional causal association between frailty and depression: A Mendelian randomization study.

BACKGROUND: Observational studies have demonstrated a strong bidirectional association between frailty and depression, but it remains unclear whether this association reflects causality. This study aimed to examine the bidirectional causal relationship between frailty and depression. METHODS: Using genome-wide association study summary data, two-sample Mendelian randomization was performed to test for the potential bidirectional causality between frailty, as defined by both the frailty index and the frailty phenotype, and depression. Several frailty-related traits were additionally investigated, including weaker hand grip strength, slower walking pace and physical inactivity. Findings were replicated using an independent depression data source and verified using multiple sensitivity analyses. RESULTS: Genetically predicted higher frailty index (odds ratio [OR], 1.86; P < 0.001), higher frailty phenotype score (OR, 2.79; P < 0.001), lower grip strength (OR, 1.23; P = 0.003), slower walking pace (OR, 1.55; P = 0.027) and physical inactivity (OR, 1.44; P = 0.003) all were associated with a higher risk of depression. As for the reverse direction, genetic liability to depression showed consistent associations with a higher frailty index (beta, 0.167; P < 0.001) and a higher frailty phenotype score (beta, 0.067; P = 0.001), but not with other frailty-related traits that were investigated. The results were stable across sensitivity analyses and across depression datasets. CONCLUSIONS: Our findings add novel evidence supporting the bidirectional causal association between frailty and depression. Improving balance and muscle strength and increasing physical activity may be beneficial in both depression and frailty.

Loop-mediated isothermal amplification (LAMP)/Cas12a assay for detection of Ralstonia solanacearum in tomato.

Introduction: Bacterial wilt (BW) caused by the aerobic, Gram-negative pathogenic species Ralstonia solanacearum (RS) is a major disease impacting commercial agriculture worldwide. Asian phylotype I of RS is the cause of tomato bacterial wilt, which has caused severe economic losses in southern China for many years. An urgent priority in control of bacterial wilt is development of rapid, sensitive, effective methods for detection of RS. Methods: We describe here a novel RS detection assay based on combination of loop-mediated isothermal amplification (LAMP) and CRISPR/Cas12a. crRNA1, with high trans-cleavage activity targeting hrpB gene, was selected out of four candidate crRNAs. Two visual detection techniques, involving naked-eye observation of fluorescence and lateral flow strips, were tested and displayed high sensitivity and strong specificity. Results and Discussion: The LAMP/Cas12a assay accurately detected RS phylotype Ⅰ in 14 test strains, and showed low detection limit (2.0 × 100 copies). RS in tomato stem tissue and soil samples from two field sites with suspected BW infection was identified accurately, suggesting potential application of LAMP/Cas12a assay as point-of-care test (POCT). The overall detection process took less than 2 h and did not require professional lab equipment. Our findings, taken together, indicate that LAMP/Cas12a assay can be developed as an effective, inexpensive technique for field detection and monitoring of RS.

Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study.

BACKGROUND: Considerable evidence has been reported that tobacco use could cause alterations in gut microbiota composition. The microbiota-gut-brain axis also in turn hinted at a possible contribution of the gut microbiota to smoking. However, population-level studies with a higher evidence level for causality are lacking. METHODS: This study utilized the summary-level data of respective genome-wide association study (GWAS) for 211 gut microbial taxa and five smoking phenotypes to reveal the causal association between the gut microbiota and tobacco smoking. Two-sample bidirectional Mendelian randomization (MR) design was deployed and comprehensively sensitive analyses were followed to validate the robustness of results. We further performed multivariable MR to evaluate the effect of neurotransmitter-associated metabolites on observed associations. RESULTS: Our univariable MR results confirmed the effects of smoking on three taxa (Intestinimonas, Catenibacterium, and Ruminococcaceae, observed from previous studies) with boosted evidence level and identified another 13 taxa which may be causally affected by tobacco smoking. As for the other direction, we revealed that smoking behaviors could be potential consequence of specific taxa abundance. Combining with existing observational evidence, we provided novel insights regarding a positive feedback loop of smoking through Actinobacteria and indicated a potential mechanism for the link between parental smoking and early smoking initiation of their children driven by Bifidobacterium. The multivariable MR results suggested that neurotransmitter-associated metabolites (tryptophan and tyrosine, also supported by previous studies) probably played a role in the action pathway from the gut microbiota to smoking, especially for Actinobacteria and Peptococcus. CONCLUSIONS: In summary, the current study suggested the role of the specific gut microbes on the risk for cigarette smoking (likely involving alterations in metabolites) and in turn smoking on specific gut microbes. Our findings highlighted the hazards of tobacco use for gut flora dysbiosis and shed light on the potential role of specific gut microbiota for smoking behaviors.

High-sensitivity biosensor based on SERS integrated with dendrimer-assisted boronic acid-functionalized magnetic nanoparticles for IL-6 detection in human serum.

High-sensitivity quantitative analysis of sepsis disease markers in circulating blood is essential for sepsis early diagnosis, rapid stratification, and interventional treatment. Herein, a high-sensitivity biosensor combining surface-enhanced Raman spectroscopy (SERS) and functionalized magnetic materials was developed to quantitatively detect interleukin-6 (IL-6), a glycoprotein disease marker closely related to sepsis. First, boronic acid-functionalized magnetic nanomaterials with high adsorption performance were synthesized by utilizing the branched polyethyleneimine to provide many binding sites for boronic acid. Under antibody-free conditions, dendrimer-assisted boronic acid-functionalized magnetic nanomaterials selectively capture glycoproteins in complex biological samples as bio-capture element. Then, a core-shell bimetallic material with plenty of 'hot spots' was designed and synthesized as the enhancement substrate. The 4-Mercaptobenzonitrile (4-MP) with a characteristic peak at 2224 cm-1(Raman-silent region) was embedded as the Raman reporter to form a SERS immune probe with highly efficient electromagnetic enhancement effect, achieving specific recognition and high-sensitivity detection of IL-6 on bio-capture elements. Using this strategy for quantitative analysis of IL-6, a wide detection range (0.5-5000 pg ml-1) and a low detection limit (0.453 pg ml-1) were obtained. Moreover, this method exhibited excellent detection performance for IL-6 in human serum samples, demonstrating its potential promise in screening clinically relevant diseases. The biosensor presented here not only provides a novel and universally applicable sensing strategy for the enrichment and detection of trace glycoprotein disease markers, but also the application of a portable Raman spectrometer provides a more reliable experimental basis for the diagnosis and treatment of major diseases in the clinic or remote and deprived areas.

Corrigendum: Involvement of the GABAergic system in PTSD and its therapeutic significance.

[This corrects the article DOI: 10.3389/fnmol.2023.1052288.].