Metabolic health and genetic predisposition in inflammatory bowel disease: Insights from a prospective cohort study.

BACKGROUND: Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. METHOD: This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. RESULTS: During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27-6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. CONCLUSION: Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.

Safety of propofol-assisted deep extubation in the dental treatment of children-a retrospective, observational study.

PURPOSE: Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed. MATERIALS AND METHODS: Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator. RESULTS: The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001). CONCLUSIONS: Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies.

Combined toxicity of polyvinyl chloride microplastics and copper to marine jacopever (Sebastes schlegelii).

Marine organisms commonly encounter co-stress resulting from the coexistence of microplastics (MPs) and heavy metals pollution in marine environments. Nevertheless, the combined effects and toxicity mechanisms of MPs and heavy metals on marine organisms remain unclear. This study integrated growth, physiological, morphological, and biochemical markers to assess the individual and combined toxicity of polyvinyl chloride MPs (PVC MPs, 1 × 104 particles/L) and copper (Cu, 200 µg/L) on marine jacopever (Sebastes schlegelii). The results revealed that co-exposure to MPs and Cu had a more detrimental impact on jacopever compared to the single-exposure groups, as evidenced by the enhanced growth inhibition, respiratory stress, and hepatotoxicity. This phenomenon may be attributed to PVC MPs accelerating the accumulation of Cu in jacopever liver. Therefore, peroxidation damage occurred in the co-exposed liver and may result in liver dysfunction. These findings contribute valuable insights into the risks associated with the coexistence of MPs and heavy metal pollution in marine ecosystems.

Predictive factors influencing outcome of early cranioplasty after decompressive craniectomy: a outcome prediction model study.

Objective: The timing of cranioplasty (CP) has become a widely debated topic in research, there is currently no unified standard. To this end, we established a outcome prediction model to explore the factors influencing the outcome of early CP. Our aim is to provide theoretical and practical basis for whether patients with skull defects after decompressive craniectomy (DC) are suitable for early CP. Methods: A total of 90 patients with early CP after DC from January 2020 to December 2021 were retrospectively collected as the training group, and another 52 patients with early CP after DC from January 2022 to March 2023 were collected as the validation group. The Nomogram was established to explore the predictive factors that affect the outcome of early CP by Least absolute shrinkage analysis and selection operator (LASSO) regression and Logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the prediction model. Calibration curve was used to evaluate the accuracy of data fitting, and decision curve analysis (DCA) diagram was used to evaluate the benefit of using the model. Results: Age, preoperative GCS, preoperative NIHSS, defect area, and interval time from DC to CP were the predictors of the risk prediction model of early CP in patients with skull defects. The area under ROC curve (AUC) of the training group was 0.924 (95%CI: 0.867-0.980), and the AUC of the validation group was 0.918 (95%CI, 0.842-0.993). Hosmer-Lemeshow fit test showed that the mean absolute error was small, and the fit degree was good. The probability threshold of decision risk curve was wide and had practical value. Conclusion: The prediction model that considers the age, preoperative GCS, preoperative NIHSS, defect area, and interval time from DC has good predictive ability.

Evidence of size-dependent toxicity of polystyrene nano- and microplastics in sea cucumber Apostichopus japonicus (Selenka, 1867) during the intestinal regeneration.

Microplastics are ubiquitous pollutants in the global marine environment. However, few studies have adequately explored the different toxic mechanisms of microplastics (MPs) and nanoplastics (NPs) in aquatic organisms. The sea cucumber, Apostichopus japonicus, is a key organism in the marine benthic ecosystem due to its crucial roles in biogeochemical cycles and food web. This study investigated the bioaccumulation and adverse effects of polystyrene micro- and nanoplastics (PS-M/NPs) of different sizes (20 µm, 1 µm and 80 nm) in the regenerated intestine of A. japonicus using multi-omics analysis. The results showed that after 30-day exposure at the concentration of 0.1 mg L-1, PS-MPs and PS-NPs accumulated to 155.41-175.04 µg g-1 and 337.95 µg g-1, respectively. This excessive accumulation led to increased levels of antioxidases (SOD, CAT, GPx and T-AOC) and reduced activities of immune enzymes (AKP, ACP and T-NOS), indicating oxidative damage and compromised immunity in the regenerated intestine. PS-NPs had more profound negative impacts on cell proliferation and differentiation compared to PS-MPs. Transcriptomic analysis revealed that PS-NPs primarily affected pathways related to cellular components, e.g., ribosome, and oxidative phosphorylation. In comparison, PS-MPs had greater influences on actin-related organization and organic compound metabolism. In the PS-M/NPs-treated groups, differentially expressed metabolites were mainly amino acids, fatty acids, glycerol phospholipid, and purine nucleosides. Additionally, microbial community reconstruction in the regenerated intestine was severely disrupted by the presence of PS-M/NPs. In the PS-NPs group, Burkholderiaceae abundance significantly increased while Rhodobacteraceae abundance decreased. Correlation analyses demonstrated that intestinal regeneration of A. japonicus was closely linked to its enteric microorganisms. These microbiota-host interactions were notably affected by different PS-M/NPs, with PS-NPs exposure causing the most remarkable disruption of mutual symbiosis. The multi-omic approaches used here provide novel insights into the size-dependent toxicity of PS-M/NPs and highlight their detrimental effects on invertebrates in M/NPs-polluted marine benthic ecosystems.

Adherence to a Mediterranean diet is associated with a lower risk of diabetic kidney disease among individuals with hyperglycemia: a prospective cohort study.

BACKGROUND: Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). METHODS: We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual's diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. RESULTS: Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. CONCLUSIONS: In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.

Diagnostic values of different musculoskeletal ultrasound signs, serum uric acid, and their combined detection for gouty arthritis.

Objectives: The study aimed to investigate the diagnostic values of different musculoskeletal ultrasound (MSUS) signs, serum uric acid (SUA), and their combined detection for gouty arthritis (GA). Patients and methods: In this retrospective study, 70 patients (62 males, 8 females; mean age: 46.1±14.1 years; range, 25 to 86 years) diagnosed with GA (the GA group) between August 2022 and March 2023 and 70 patients (54 females, 16 males; mean age: 49.0±14.1 years; range, 21 to 75 years) diagnosed with rheumatoid arthritis and osteoarthritis during the same period (the non-GA group) were included. The positive rate of MSUS signs and SUA in both groups was recorded to compare the differences. The correlations of MSUS signs and SUA with GA were analyzed using Spearman's rank correlation analysis. The diagnostic values of different MSUS signs, SUA, and their combined detection for GA were analyzed using a receiver operating characteristic, the area under the curve (AUC), sensitivity, specificity, and the Youden index. Results: The positive rate of the double contour (DC) sign (chi-squared [χ2 ]=102.935, p<0.001), hyperechoic spots (χ2=56.395, p<0.001), bone erosions (χ2 =10.080, p<0.001), and SUA (χ2 =41.117, p <0.001) were higher in the GA group than in the non-GA group. The positive rate of the DC sign (rs=0.829, p=0.001), hyperechoic spots (rs=0.631, p<0.001), bone erosion (rs=0.268, p=0.001), and SUA (rs=0.542, p<0.001) were positively correlated with GA. Among the single-indicator measures, the DC sign exhibited the highest diagnostic value (AUC=0.907, sensitivity=81.4%, specificity=100%, p<0.001). Among the combined-indicator measures, the DC sign combined with SUA exhibited the highest diagnostic value (AUC=0.929, sensitivity=91.4%, specificity=94.3%, p<0.001), higher than DC sign detection alone. Conclusion: The DC sign combined with SUA yielded a high diagnostic value and can thus provide a reliable basis for effectively and efficiently diagnosing GA.

An Approach to Constructing Multispecies Biofilm Communities from Rhizosphere Soil.

The multispecies biofilm is a naturally occurring and dominant lifestyle of bacteria in nature, including in rhizosphere soil, although the current understanding of it is limited. Here, we provide an approach to rapidly establish synergistic multispecies biofilm communities. The first step is to extract cells from rhizosphere soil using the differential centrifugation method. Afterward, these soil cells are inoculated into the culture medium to form pellicle biofilm. After 36 h of incubation, the bacterial composition of the biofilm and the solution underneath are determined using the 16S rRNA gene amplicon sequencing method. Meanwhile, high-throughput bacterial isolation from pellicle biofilm is conducted using the limiting dilution method. Then, the top 5 bacterial taxa are selected with the highest abundance in the 16S rRNA gene amplicon sequencing data (pellicle biofilm samples) for further use in constructing multispecies biofilm communities. All combinations of the 5 bacterial taxa were quickly established using a 24-well plate, selected for the strongest biofilm formation ability by the crystal violet staining assay, and quantified by qPCR. Finally, the most robust synthetic bacterial multispecies biofilm communities were obtained through the methods above. This methodology provides informative guidance for conducting research on rhizosphere multispecies biofilm and identifying representative communities for studying the principles governing interactions among these species.

Regulatory effects of stress release from decellularized periosteum on proliferation, migration, and osteogenic differentiation of periosteum-derived cells.

Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the biological effects of periosteal prestress release on periosteum-derived cells (PDCs) and the potential mechanisms of endogenous stem cell recruitment. Decellularized periosteum with natural extracellular matrix (ECM) components was obtained by a combination of physical, chemical, and enzymatic decellularization. The decellularized periosteum removed immunogenicity while retaining the natural network structure and composition of the ECM. The Young's modulus has no significant difference between the periosteum before and after decellularization. The extracted PDCs were further composited with the decellularized periosteum and subjected to 20% stress release. It was found that the proliferative capacity of PDCs seeded on decellularized periosteum was significantly enhanced 6 h after stress release of the periosteum. The cell culture supernatant obtained after periosteal prestress release was able to significantly promote the migration ability of PDCs within 24 h. Enzyme-linked immunosorbnent assay (ELISA) experiments showed that the expression of stroma-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in the supernatant increased significantly after 3 h and 12 h of stress release, respectively. Furthermore, periosteal stress release promoted the high expression of osteogenic markers osteocalcin (OCN), osteopontin (OPN), and collagen type I of PDCs. The change in stress environment caused by the release of periosteal prestress was sensed by integrin ß1, a mechanoreceptor on the membrane of PDCs, which further stimulated the expression of YAP in the nucleus. These investigations provided a novel method to evaluate the importance of mechanical stimulation in periosteum, which is also of great significance for the design and fabrication of artificial periosteum with mechanical regulation function.

Association of coffee and tea consumption with osteoporosis risk: A prospective study from the UK biobank.

OBJECTIVE: The association of coffee and tea consumption with osteoporosis is highly controversial, and few studies have focused on the combined effects of the two beverages. This study aimed to investigate the independent and combined associations of coffee and tea consumption with osteoporosis risk. METHODS: A prospective cohort study involving 487,594 participants aged 38-73 years from the UK Biobank was conducted. Participants with reported coffee and tea consumption and without osteoporosis at baseline were included. Coffee and tea consumption were assessed via a touch-screen questionnaire at baseline. Newly diagnosed osteoporosis during the follow-up period, defined based on ICD-10 codes (M80-M82), was the primary outcome. Cox regression analyses were utilized to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). Dose-effect associations were assessed using restricted cubic spline analysis. RESULTS: During a median follow-up of 12.8 years, 15,211 cases of osteoporosis were identified. Compared to individuals without coffee or tea consumption, drinking coffee was associated with an HR of 0.93 (95 % CI: 0.89-0.96), and tea consumption with an HR of 0.86 (95 % CI: 0.83-0.90). Continuous trends were significant for both coffee and tea consumption, showing non-linear associations with osteoporosis incidence. Moderate consumption, such as 1-2 cups of coffee or 3-4 cups of tea per day, was associated with a lower incidence of osteoporosis, with HRs of 0.9 (95 % CI: 0.86-0.94) and 0.85 (95 % CI: 0.81-0.90), respectively. Additionally, combined coffee and tea consumption displayed a U-shaped association with osteoporosis risk, with the lowest risk observed in individuals who consumed 1-2 cups of both beverages daily, with an HR of 0.68 (95 % CI: 0.61-0.75). CONCLUSION: Our findings highlight the potential benefits of moderate coffee and tea consumption in reducing the risk of osteoporosis.

Bioaccumulation of polycyclic aromatic hydrocarbons and their human health risks depend on the characteristics of microplastics in marine organisms of Sanggou Bay, China.

Microplastics pose a threat to marine environments through their physical presence and as vectors of chemical pollutants. However, the impact of microplastics on the accumulation and human health risk of chemical pollutants in marine organisms remains largely unknown. In this study, we investigated the microplastics and polycyclic aromatic hydrocarbons (PAHs) pollution in marine organisms from Sanggou Bay and analyzed their correlations. Results showed that microplastic and PAHs concentration ranged from 1.23 ± 0.23 to 5.77 ± 1.10 items/g, from 6.98 ± 0.45 to 15.07 ± 1.25 µg/kg, respectively. The microplastic abundance, particularly of fibers, transparent and color plastic debris, correlates strongly with PAH contents, indicating that microplastics increase the bioaccumulation of PAHs and microplastics with these characteristics have a significant vector effect on PAHs. Although consuming seafood from Sanggou Bay induce no carcinogenic risk from PAHs, the presence of microplastics in organisms can significantly increases incremental lifetime cancer risk of PAHs. Thus, microplastics can serve as transport vectors for PAHs with implications for the potential health risks to human through consumption. This study provides new insight into the risks of microplastics in marine environments.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

The Dominant Role of Recrystallization and Grain Growth Behaviors in the Simulated Welding Heat-Affected Zone of High-Mn Steel.

Single-pass-welding thermal cycles with different peak temperatures (Tp) were reproduced by a Gleeble 3800 to simulate the heat-affected zone (HAZ) of a Fe-24Mn-4Cr-0.4C-0.3Cu (wt.%) high manganese austenitic steel. Then, the effect of Tp on the microstructure and mechanical properties of the HAZ were investigated. The results indicate that recrystallization and grain growth play dominant roles. Based on this, the HAZ is proposed to categorize into three zones: the recrystallization heat-affected zone (RHAZ) with a Tp of 700~900 °C, the transition heat-affected zone (THAZ) with a Tp of 900~1000 °C, and the coarse grain heat-affected zone (CGHAZ) with a Tp of 1000~1300 °C. The recrystallization fraction was 29~44% in the RHAZ, rapidly increased to 87% in the THAZ, and exceeded 95% in the CGHAZ. The average grain size was 17~19 µm in the RHAZ, slightly increased to 22 µm in the THAZ, and ultimately increased to 37 µm in the CGHAZ. The yield strength in the RHAZ and THAZ was consistent with the change in recrystallization fraction, while in the CGHAZ, it satisfied the Hall-Petch relationship with grain size. In addition, compared with the base material, the Charpy impact absorbed energy at -196 °C decreased by 22% in the RHAZ, but slightly increased in the CGHAZ. This indicates that the theory of fine grain strengthening and toughening is not entirely applicable to the HAZ of the investigated high-Mn steel.

Deep learning-based detection of irreversible pulpitis in primary molars.

BACKGROUND: Changes in healthy and inflamed pulp on periapical radiographs are traditionally so subtle that they may be imperceptible to human experts, limiting its potential use as an adjunct clinical diagnostic feature. AIM: This study aimed to investigate the feasibility of an image-analysis technique based on the convolutional neural network (CNN) to detect irreversible pulpitis in primary molars on periapical radiographs (PRs). DESIGN: This retrospective study was performed in two health centres. Patients who received indirect pulp therapy at Peking University Hospital for Stomatology were retrospectively identified and randomly divided into training and validation sets (8:2). Using PRs as input to an EfficientNet CNN, the model was trained to categorise cases into either the success or failure group and externally tested on patients who presented to our affiliate institution. Model performance was evaluated using sensitivity, specificity, accuracy and F1 score. RESULTS: A total of 348 PRs with deep caries were enrolled from the two centres. The deep learning model achieved the highest accuracy of 0.90 (95% confidence interval: 0.79-0.96) in the internal validation set, with an overall accuracy of 0.85 in the external test set. The mean greyscale value was higher in the failure group than in the success group (p = .013). CONCLUSION: The deep learning-based model could detect irreversible pulpitis in primary molars with deep caries on PRs. Moreover, this study provides a convenient and complementary method for assessing pulp status.

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration.

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury.

Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.

Highly stable mixed-phase Cs-Cu-I films with tunable optoelectronic properties for UVB photodetector applications.

Ultraviolet (UV) photodetector plays an important role in military, civilian and people's daily life, and is an indispensable part of spectral detection. However, photodetectors target at the UVB region (280-320 nm) are rarely reported, and the devices detected by medium-wave UV light generally have problems such as low detection rate, low sensitivity, and poor stability, which are difficult to meet the market application needs. Herein, Cs-Cu-I films with mixed-phase have been prepared by vacuum thermal evaporation. By adjusting the proportion of evaporation sources (CsI and CuI), the optical bandgaps of mixed-phase Cs-Cu-I films can be tuned between 3.7 eV and 4.1 eV. This absorption cut-off edge is exactly at both ends of the UVB band, which indicating its potential application in the field of UVB detection. Finally, the photodetectors based on Cs-Cu-I/n-Si heterojunction are fabricated. The photodetector shows good spectral selectivity for UVB band, and has a photoresponsivity of 22 mA/W, a specific detectivity of 1.83*1011 Jones, an EQE over 8.7% and an on/off ratio above 20.

Individualized prevention of proton pump inhibitor related adverse events by risk stratification.

Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.

Chromosome-level genome of Thymus mandschuricus reveals molecular mechanism of aroma compounds biosynthesis.

Background: Thymus mandschuricus is an aromatic and medicinal plant with notable antibacterial and antioxidant properties. However, traditional breeding methods rely on phenotypic selection due to a lack of molecular resources. A high-quality reference genome is crucial for marker-assisted breeding, genome editing, and molecular genetics. Results: We utilized PacBio and Hi-C technologies to generate a high-quality chromosome-level reference genome for T. mandschuricus, with a size of 587.05 Mb and an N50 contig size of 8.41 Mb. The assembled genome contained 29,343 predicted protein-coding genes, and evidence of two distinct whole-genome duplications in T. mandschuricus was discovered. Comparative genomic analysis revealed rapid evolution of genes involved in phenylpropanoid biosynthesis and the CYP450 gene family in T. mandschuricus. Additionally, we reconstructed the gene families of terpenoid biosynthesis structural genes, such as TPS, BAHD, and CYP, and identified regulatory networks controlling the expression of aroma-synthesis genes by integrating transcriptome data from various organs and developmental stages. We discovered that hormones and transcription factors may collaborate in controlling aroma-synthesis gene expression. Conclusion: This study provides the first high-quality genome sequence and gene annotation for T. mandschuricus, an indigenous thyme species unique to China. The genome assembly and the comprehension of the genetic basis of fragrance synthesis acquired from this research could potentially serve as targets for future breeding programs and functional studies.

Alterations in gut microbiota and bile acids by proton-pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance.

Several observational studies have suggested that proton-pump inhibitor (PPI) use might increase diabetes risk, but the mechanism remains unclear. This study aimed to investigate the effects of PPI use on gut microbiota and bile acids (BAs) profiles, and to explore whether these changes could mediate the association of PPIs use with fasting blood glucose (FBG) levels and insulin resistance (IR) in Chinese population. A cross-sectional study was conducted in Shenzhen, China, from April to August 2021, enrolled 200 eligible patients from the local hospital. Participants completed a questionnaire and provided blood and stool samples. Gut microbiome was measured by16S rRNA gene sequencing, and bile acids were quantified by UPLC-MS/MS. Insulin resistance (IR) was assessed using the Homeostasis Model Assessment 2 (HOMA2-IR). PPI use was positively associated with higher levels of FBG and HOMA2-IR after controlling for possible confounders. PPI users exhibited a decreased Firmicutes and an increase in Bacteroidetes phylum, alongside higher levels of glycoursodeoxycholic acid (GUDCA) and taurochenodeoxycholic acid (TCDCA). Higher abundances of Bacteroidetes and Fusobacterium as well as higher levels of TCDCA in PPI users were positively associated with elevated FBG or HOMA2-IR. Mediation analyses indicated that the elevated levels of FBG and HOMA2-IR with PPI use were partially mediated by the alterations in gut microbiota and specific BAs (i.e., Fusobacterium genera and TCDCA). Long-term PPI use may increase FBG and HOMA2-IR levels, and alterations in gut microbiota and BAs profiles may partially explain this association.