Predicting functional UTR variants by integrating region-specific features.

The untranslated region (UTR) of messenger ribonucleic acid (mRNA), including the 5'UTR and 3'UTR, plays a critical role in regulating gene expression and translation. Variants within the UTR can lead to changes associated with human traits and diseases; however, computational prediction of UTR variant effect is challenging. Current noncoding variant prediction mainly focuses on the promoters and enhancers, neglecting the unique sequence of the UTR and thereby limiting their predictive accuracy. In this study, using consolidated datasets of UTR variants from disease databases and large-scale experimental data, we systematically analyzed more than 50 region-specific features of UTR, including functional elements, secondary structure, sequence composition and site conservation. Our analysis reveals that certain features, such as C/G-related sequence composition in 5'UTR and A/T-related sequence composition in 3'UTR, effectively differentiate between nonfunctional and functional variant sets, unveiling potential sequence determinants of functional UTR variants. Leveraging these insights, we developed two classification models to predict functional UTR variants using machine learning, achieving an area under the curve (AUC) value of 0.94 for 5'UTR and 0.85 for 3'UTR, outperforming all existing methods. Our models will be valuable for enhancing clinical interpretation of genetic variants, facilitating the prediction and management of disease risk.

Apoptosis and NETotic cell death affect diabetic nephropathy independently: An study integrative study encompassing bioinformatics, machine learning, and experimental validation.

OBJECTIVE: Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis. METHODS: We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies. RESULTS: We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, p < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification. CONCLUSION: Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for future research.

4.3†µm high-power amplified spontaneous emission fiber source based on CO2-filled nested hollow-core anti-resonant fiber.

We report a 4.3 µm mid-infrared (mid-IR) high-power amplified spontaneous emission (ASE) fiber source based on CO2-filled nested hollow-core anti-resonant fiber (Nested HC-ARF). The pump source is a homemade hundred-watt-level wavelength-tunable 2 µm single-frequency fiber laser. A 5.7 m long 8-tube Nested HC-ARF is used as the gas cell, with a core diameter of 110 µm and cladding diameter of 400 µm, which exhibits transmission loss of 0.1 dB/m at 2 µm and 0.24 dB/m at 4.3 µm respectively. To improve the coupling efficiency of the high-power pump laser and reduce the influence of the thermal effect at the input end of the hollow-core fiber, the fiber is designed for multimode transmission at the pump wavelength. A continuous wave output power of 6.6 W at 4.3 µm is achieved, and the slope efficiency is 17.05%. To the best of our knowledge, it is the highest output power for such gas-filled HC-ARF ASE sources in 4∼5 µm. This work demonstrates the great potential of gas-filled HC-ARF generating high-power mid-IR emission.

Long-term outcomes of left atrial appendage closure with or without concomitant pulmonary vein isolation:a propensity score matching analysis based on CLACBAC study.

BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.

Prevalence of Parkinson's disease among adults aged 45 years and older in China: a cross-sectional study based on the China health and retirement longitudinal study.

BACKGROUND: In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China. Cases were established based on a doctor's previous diagnosis. Crude and age-adjusted prevalence rates were calculated and stratified by age, sex, area of residence, education level, marital status, and geographic region. Logistic regression models were used to identify risk factors associated with PD. RESULTS: We identified 178 patients with PD among 19,034 residents aged 45 years and older. The crude prevalence was 0.94%, and the age-adjusted prevalence was 0.82% for individuals aged 45 years and older. The prevalence of PD increased with age (P < 0.001). No significant differences were found in terms of sex, area of residence, or education level. Stratified by geographic region, the prevalence of PD was greater in North and Northwest China and lower in southern China (p < 0.001). Multiple regression analyses showed that age was a significant risk factor for PD. CONCLUSION: The prevalence of PD increased with age in the Chinese population.

Isolated Coordination Polyhedron Confinement in ABP2O7:Mn2+ (A = Ba/Sr; B = Mg/Zn).

Many research efforts have focused on designing new inorganic phosphors to meet different application requirements. The structure-photoluminescence relationship between activator ions and the matrix lattice plays an irreparable role in designing target phosphors. Herein, a series of ABP2O7:Mn2+ (A = Ba/Sr; B = Mg/Zn) phosphors are prepared for a detailed study on the relationship between the luminescence performance and spatial structure and symmetry of the doping site of Mn2+. Due to the weak interaction between nearest B-B pairs, [BO5] is defined as an isolated coordination polyhedron whose structure and symmetry directly influence the photoluminescence of Mn2+. The emission wavelength of Mn2+ is ∼620 nm when it occupies the triangular bipyramid [MgO5] in BaMgP2O7. When Mn2+ occupies the quadrangular pyramid-typed [MgO5] or [ZnO5] in SrMgP2O7, SrZnP2O7, and BaZnP2O7, the emission wavelengths peak at ∼670 nm. We propose a conception of isolated coordination polyhedral confinement to clarify the luminescence performance of Mn2+ in the fivefold coordination configuration with different geometries, which has great theoretical research significance for designing inorganic phosphors.

Effectiveness of inspector mechanism for the emergency infection prevention and control in the SARS-CoV-2 epidemic period: a self-control real-word study.

BACKGROUND: To ensure emergency infection prevention and control (IPC) can be fully supervised and monitored in coronavirus disease (COVID-19) epidemic period, a three-level inspector mechanism called "Internal self-check, Departmental cross-check, and Verification of outstanding key and difficult issues" was established in southwest China. The present study aimed to explore the effectiveness of inspector mechanism for the emergency IPC. METHODS: A self-control real-world study was conducted during COVID-19 epidemic period from 2020 to 2022. An innovative designed mobile phone application was used to realize paperless information transmission and data management. Data were compared between inspection levels using SPSS 19.0 software. RESULTS: A total of 2,800,132 supervision records were collected, including 149,137 comprehensive epidemic IPC projects, 1,410,093 personal protective equipment (PPE) use, 1,223,595 wearing and removing process of PPE and 17,307 ultraviolet light-detectable fluorescent (UV/F) surface marker. During the study period, the inspectors and subjects explored many optimized IPC measures. The compliance rate of check items has exceeded 98%, and internal self-check has a statistically significant higher rate than departmental cross-check (99.95% versus 98.74%, χ2 = 26111.479, P < 0.001). Compare with the failure rate in internal self check, the failure rate of PPE usage and wearing/removing process was statistically higher in departmental cross-check (χ2 = 1957.987, P < 0.001, χ2 = 465.610, P < 0.001, respectively). The overall clearance rate of UV/F surface markers is 87.88%, but there is no statistically significant difference over the three years of the present study (F = 2.902, P = 0.071). CONCLUSIONS: Inspector mechanism for the emergency IPC completed an incredible inspection workload and offered creative assistance to combat the COVID-19 outbreak. These methods and accumulated experiences should be helpful for us to strengthen IPC for future epidemic.

Chitosan based smart polymer composites: Fabrication and pH-Responsive behavior for bio-medical applications.

This research aimed to synthesize Chitosan/PVA-blank and a series of Cs/PVA/Sepolite based pH-sensitive membranes using a solution casting process. The synthesized Cs/PVA-blank and Cs/PVA/Sep based membranes were investigated via SEM, FTIR, XRD, and TGA techniques. The SEM results of Cs/PVA/Sep based membrane reveal that the hydrolytic stability and strength were improved in acidic and basic media owing to the incorporation of sepiolite content into chitosan. The characteristic band at 3741 cm-1 in the FTIR spectra of the Cs/PVA/Sep membrane confirmed the successful synthesis. The obtained XRD results showed higher d-spacing for Cs/PVA/Sep membranes as compared to the Cs/PVA-blank membranes owing to the intercalation of chitosan in the interlayer spacing of the sepiolite. The obtained TGA results show higher thermally stability for Cs/PVA/Sep membrane as compared to the Cs/PVA-blank sample due to the interaction of sepiolite content with the chitosan matrix. The obtained hydrolytic and swelling studies revealed that the Cs/PVA/Sep membrane displayed enhanced stability in basic and neutral media while showing minimum swelling in an acidic medium. The water uptake ability was checked for Cs/PVA/-blank and Cs/PVA/Sep-60% membrane and the results exhibited that the Cs/PVA/-blank membrane had maximum water uptake value as compared to the Cs/PVA/Sep-60% membrane. While those with a considerable amount of filler had the lowest water uptake values. As Sepolite content increased, the water uptake % values decreases because of weakness in H-bonding (of hydrophilic groups) and due to intercalation in Sepolite layers during polymer formation.

Glucagon-Like Peptide-2 Ameliorates Age-Associated Bone Loss and Gut Barrier Dysfunction in Senescence-Accelerated Mouse Prone 6 Mice.

INTRODUCTION: Senile osteoporosis is one of the most common age-related diseases worldwide. Glucagon like peptide-2 (GLP-2), a naturally occurring gastrointestinal peptide, possesses therapeutic effects on bone loss in postmenopausal women and ovariectomized rats. However, the role of GLP-2 in senile osteoporosis and underlying mechanisms has not been explored. METHODS: GLP-2 was subcutaneously injected into the 6-month-old male senile osteoporosis model of senescence-accelerated mouse prone 6 (SAMP6) mice for 6 weeks. SAMP6 subjected to normal saline and senescence-accelerated mouse resistant 1 served as control groups. Micro-computed tomography was performed to evaluate the bone mass and microarchitecture of the mice. Osteoblastic and osteoclastic activities were determined by biochemical, quantitative real-time PCR, histological, and histomorphometric analyses combined with hematoxylin-eosin, toluidine blue, and tartrate-resistant acid phosphatase staining. We also examined the proteins and structure of intestinal tight junction using immunohistochemical assay as well as a transmission electron microscope. Serum inflammation marker levels were measured using ELISA. Additionally, anti-oxidative enzymes GPX-4 and SOD-2 and receptors of GLP-2 and vitamin D expression in the ileum and colon were detected under immunofluorescence staining. RESULTS: Six-week GLP-2 treatment attenuated bone loss in SAMP6 mice, as evidenced by increased bone mineral density, improved microarchitecture in femora, and enhanced osteogenic activities. In contrast, the activity of osteoclastic activity was not obviously inhibited. Moreover, GLP-2 ameliorated tight junction structure and protein expression in the intestinal barrier, which was accompanied by the reduction of TNF-α level. The expression of receptors of intestinal GLP-2 and vitamin D in the ileum was elevated. Furthermore, the oxidative stress in the intestines was improved by increasing the GPX-4 and SOD-2 signaling. CONCLUSION: Our findings suggest that GLP-2 could ameliorate age-associated bone loss, tight junction structure, and improved antioxidant enzyme activity in the gut in SAMP6 mice. Amelioration of gut barrier dysfunction may potentially contribute to improving bone formation and provide evidence for targeting the entero-bone axis in the treatment of senile osteoporosis.

Identification of six novel mutations in EDA from 20 hypohidrotic ectodermal dysplasia families.

OBJECTIVE: To investigate the genetic causes of 22 patients with clinically high suspicion of X-linked hypohidrotic ectodermal dysplasia from 20 unrelated Chinese families, expand the spectrum of ectodysplasin-A mutations, and provide more evidence for variants of uncertain significance. SUBJECTS AND METHODS: Whole-exome sequencing was performed and potentially pathogenic variants were verified by Sanger sequencing. Western blotting, real-time PCR and immunofluorescence analyses were performed to investigate the preliminary functions of the candidate variants. RESULTS: Nineteen ectodysplasin-A variants were identified, six of which were not previously reported. Among these variants, we identified a patient who carried two mutations in ectodysplasin-A and exhibited more severe phenotypes. Additionally, mutant protein expression levels decreased, whereas mRNA transcription levels increased. Cellular sublocalisation of the variants located in the tumour necrosis factor homologous domain showed that the proteins accumulated in the nucleus, whereas wild-type proteins remained in the cell membrane. A rare indel variant and two classical splicing variants that lead to exon 7 skipping were detected. CONCLUSIONS: This study provides definitive diagnoses for 20 families with suspected X-linked hypohidrotic ectodermal dysplasia and additional information on clinical heterogeneity and genotype-phenotype relationships.

The Relationship between Skeletal Muscle Mass and Bone Mass at Different Sites in Older Adults.

INTRODUCTION: It has been well recognized that sarcopenia is closely related with osteoporosis, while the relationship between bone mass at different sites and muscle mass remains largely unexplored. This study aims to explore the relationship between bone mass at different sites and skeletal muscle mass in older adults. METHODS: A total of 228 patients over 65 years old were enrolled in this study, and then 180 valid participants with accessible dual-energy X-ray absorptiometry (DXA) scanning data and absence of malignant tumors, mobility disorders, serious liver and kidney disease, and cardiac insufficiency were selected (138 male and 42 female). These individuals were further divided into control group and low skeletal muscle mass index (SMI) group. DXA scanning was used to access skeletal muscle mass and bone mass. SMI or body mass index was defined as appendicular muscle mass or weight divided by squared height, respectively. Low SMI <7.0 kg/m2 in male or <5.4 kg/m2 in female was defined as low SMI; while the bone density score at or below 2.5 standard deviations (T-score) below normal peak bone values, was regarded as osteoporosis. RESULTS: The average age of enrolled patients was 82.72 years; the ratios of osteoporosis, low SMI, and low SMI with osteoporosis were 48.8%, 23.3%, and 15.0%, respectively. Compared with the control group, the prevalence of osteoporosis was higher, and the total bone mass and bone mass at various sites including limbs, spine, and pelvis, were all lower in low SMI group. Correlation analysis showed that SMI was positively related with total bone mass and bone mass at various sites. Covariance analysis showed that only total bone mass and appendicular bone mass decreased with decreasing SMI. After multiple adjustment, osteoporosis was positively related with the prevalence of low SMI, as evidenced by logistic regression analysis (odds ratio = 1.33, 95% confidential interval: 1.04-3.24, p = 0.045). Furthermore, compared with the highest quartile of appendicular bone mass, the lowest quartile was related with the increasing prevalence of low SMI (odds ratio = 7.29, 95% confidential interval: 1.21-67.45, p = 0.042). CONCLUSION: Compared with the other sites, the bone mass reduction at limbs of older adults was positively associated with skeletal muscle loss. It may be more beneficial to increase bone mass at the limbs for improved sarcopenia prevention and therapy. Further investigations are needed to explore the effects of other confounders (e.g., energy, calcium and vitamin D intake, and physical activity) on the osteoporosis and sarcopenia in older adults.

Potential of technological innovation to reduce the carbon footprint of urban facility agriculture: A food-energy-water-waste nexus perspective.

As an emerging form of agriculture, urban facility agriculture is an important supplement to traditional agriculture and one of the ways to alleviate the urban food crisis, but it may generate a high carbon footprint. A comprehensive assessment of urban facility agriculture is a necessity for promoting its low-carbon development. In this study, the carbon footprint of urban facility agriculture under four different technological innovation models was simulated by life cycle assessment and a system dynamics model for a carbon footprint accounting without considering economic risk. Case 1, as the basic case, is Household farm facility agriculture. Case 2 is the introduction of vertical hydroponic technology based on Case 1, Case 3 is the introduction of distributed hybrid renewable energy micro-grid technology based on Case 2, and Case 4 is the introduction of automatic composting technology based on Case 3. These four cases demonstrate the gradual optimization of the food-energy-water-waste nexus in urban facility agriculture. This study further uses the system dynamics model for carbon reduction potential considering economic risk to simulate the diffusion (promotion) scale and carbon reduction potential of different technological innovations. Research results show that with the superposition of technologies, the carbon footprint per unit land area is gradually reduced, and the carbon footprint of Case 4 is the lowest at 4.78e+06 kg CO2eq. However, the gradual superposition of technologies will further limit the diffusion scale of technological innovation, thereby reducing the carbon reduction potential of technological innovation. In Chongming District, Shanghai, under theoretical circumstances, the carbon reduction potential of Case 4 is the highest at 1.6e+09 kg CO2eq, but the actual carbon reduction potential is only 1.8e+07 kg CO2eq due to excessive economic risks. By contrast, the actual carbon reduction potential of Case 2 is the highest with 9.6e+08 kg CO2eq. To fully achieve the carbon reduction potential of technology innovation, it is necessary to promote the scale diffusion of Urban facility agricultural technology innovation by raising the sales price of agricultural products and the grid connection price of renewable electricity.

The effect of root canal treatment and post-crown restorations on stress distribution in teeth with periapical periodontitis: a finite element analysis.

AIM: To evaluate the effects of root canal treatment (RCT) and post-crown restoration on stress distribution in teeth with periapical bone defects using finite element analysis. METHODOLOGY: Finite element models of mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using digital model design software. The corresponding RCT and post-crown restoration models were constructed based on the different sizes of periapical bone defect models. The von Mises stress and tooth displacement distributions were comprehensively analyzed in each model. RESULTS: Overall analysis of the models: RCT significantly increased the maximum von Mises stresses in teeth with periapical bone defects, while post-crown restoration greatly reduced the maximum von Mises stresses. RCT and post-crown restoration slightly reduced tooth displacement in the affected tooth. Internal analysis of tooth: RCT dramatically increased the maximum von Mises stress in all regions of the tooth, with the most pronounced increase in the coronal surface region. The post-crown restoration balances the internal stresses of the tooth and is most effective in periapical bone defect - 20-mm model. RCT and post-crown restoration slightly reduced the tooth displacement in all regions of the affected tooth. CONCLUSIONS: Root canal treatment seemed not to improve the biomechanical state of teeth with periapical bone defects. In contrast, post-crown restoration might effectively balance the stress concentrations caused by periapical bone defects, particularly extensive ones.

Magnetic Resonance Imaging-Based Structural Covariance Changes of the Striatum in Lifelong Premature Ejaculation Patients.

BACKGROUND: The striatum has been reported to be implicated in various neurological diseases, including lifelong premature ejaculation (LPE). Altered striatum-related functional connectivity was investigated in LPE patients in previous studies; however, structural abnormalities in the striatum have been less studied in LPE. PURPOSE: To identify the gray matter volume (GMV) and structural covariance patterns of the striatum between LPE patients and healthy controls (HCs). STUDY TYPE: Prospective. SUBJECTS: Forty-three LPE patients and 31 male HCs. FIELD STRENGTH/SEQUENCE: 3.0 T magnetic resonance imaging (MRI) scanner; T1-weighted imaging using a spoiled gradient recalled echo sequence. ASSESSMENT: Preprocessing of structural MRI data and the striatum-seeded GMV computation were conducted using SPM12. STATISTICAL TESTS: Two sample t-test was used to compare differences in GMV of the striatum between patients and HCs. Regions showing altered between-group GMV were considered as seeds for structural covariance analysis in two groups. Additionally, correlations between GMV findings and clinical features were assessed with age and total intracranial volume (TIV) as covariates and with age, TIV, anxiety, and depression scores as covariates in the patient group, P < 0.05 was considered statistically significant. RESULTS: Compared to HCs, LPE patients had significantly decreased GMV in four regions located in the bilateral caudate and putamen. Distinct striatum-based structural covariance patterns in the two groups were mainly related to the thalamus, amygdala, insula, anterior cingulate cortex, middle cingulate cortex, medial prefrontal cortex, primary motor cortex, and precuneus/cuneus. LPE patients showed that GMV in the bilateral caudate negatively correlated with the premature ejaculation diagnostic tool (PEDT) scores (r = -0.369, r = -0.377, respectively). DATA CONCLUSION: Our findings indicated that LPE patients had altered GMV and structural covariance patterns in the striatum compared to HCs. The correlations between abnormal GMV and PEDT were also shown in the present findings. These findings may contribute to enhancing the understanding of the pathophysiology of LPE. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Gray matter microstructural alterations in manganese-exposed welders: a preliminary neuroimaging study.

OBJECTIVES: Chronic occupational manganese (Mn) exposure is characterized by motor and cognitive dysfunction. This study aimed to investigate structural abnormalities in Mn-exposed welders compared to healthy controls (HCs). METHODS: Thirty-five HCs and forty Mn-exposed welders underwent magnetic resonance imaging (MRI) scans in this study. Based on T1-weighted MRI, the voxel-based morphometry (VBM), structural covariance, and receiver operating characteristic (ROC) curve were applied to examine whole-brain structural changes in Mn-exposed welders. RESULTS: Compared to HCs, Mn-exposed welders had altered gray matter volume (GMV) mainly in the medial prefrontal cortex, lentiform nucleus, hippocampus, and parahippocampus. ROC analysis indicated the potential highest classification power of the hippocampus/parahippocampus. Moreover, distinct structural covariance patterns in the two groups were associated with regions, mainly including the thalamus, insula, amygdala, sensorimotor area, and middle temporal gyrus. No significant relationships were found between the findings and clinical characteristics. CONCLUSIONS: Our findings showed Mn-exposed welders had changed GMV and structural covariance patterns in some regions, which implicated in motivative response, cognitive control, and emotional regulation. These results might provide preliminary evidence for understanding the pathophysiology of Mn overexposure. KEY POINTS: • Chronic Mn exposure might be related to abnormal brain structural neural mechanisms. • Mn-exposed welders had morphological changes in brain regions implicated in emotional modulation, cognitive control, and motor-related response. • Altered gray matter volume in the hippocampus/parahippocampus and putamen might serve as potential biomarkers for Mn overexposure.

Site Preference-Driven Mn4+ Stabilization in Double Perovskite Phosphor Regulating Quantum Efficiency from Zero to Champion.

The tetravalent-state stability of manganese is of primary importance for Mn4+ luminescence. Double perovskite-structured A2B'B″O6:Mn4+ has been recently prevalent, and the manganese ions are assumed to substitute for the B″(IV-VI)O6 site to stabilize at the tetravalent charge state to generate far-red emissions. However, some Mn-doped A2B'B″O6-type materials show no or weak luminescence such as typical Ca2MgWO6:Mn. In this work, a cation-pair co-substitution strategy is proposed to replace 2Ca2+ by Na+-La3+ to form Ca2-2xNaxLaxMgWO6:Mn. The significant structural distortion appears in the solid solution lattices with the contraction of [MgO6] but enlargement of [WO6] octahedron. We hypothesize that the site occupancy preference of Mn migrates from Mg2+ to W6+ sites. As a result, the effective Mn4+/Mn2+ concentration enhances remarkably to regulate nonluminescence to highly efficient Mn4+-related far-red emission. The optimal CaNa0.5La0.5MgWO6:0.9%Mn4+ shows an internal quantum efficiency of 94% and external quantum efficiency of 82%, reaching up to the top values in Mn4+-doped oxide phosphors. This work may provide a new perspective for the rational design of Mn4+-activated red phosphors, primarily considering the site occupancy modification and tetravalent-state stability of Mn.

Peripherally inserted central catheters have a protective role and the effect of fluctuation curve feature in the risk of bloodstream infection compared with central venous catheters: a propensity-adjusted analysis.

BACKGROUND: The prevention of peripherally inserted central catheters (PICC)-associated BSI and central venous catheters (CVC)-associated BSI have been a topic of national importance in China. Therefore, we aimed to explore the epidemiological characteristics of central line-associated bloodstream infection (CLABSI), and to evaluate whether PICCs were associated with a protective effect for CLABSI. METHODS: A retrospective cohort study was conducted in teaching hospital in Western China. All adult patients received a CVC or PICC during their hospital stay were included from January 2017 to December 2020. Primary endpoint was CLABSI up to 30 days after CVC or PICC placement. Propensity scores with a 2:1 match was used to account for potential confounders, and restricted cubic spline was used to visualize the risk of CLABSI at different time points during the catheterization. RESULTS: A total of 224687 devices (180522 PICCs and 45965 CVCs) in 24879 patients were included. The overall incidence was 1.8 CLABSIs per 1000 catheter-days. The odds ratio (OR) value increased day by day after PICC insertion, reached a relatively high point on the 4th day, and decreased from days 5 through 8. From the 9th day of intubation the OR value began to gradually increase day by day again. After covariate adjustment using propensity scores, CVCs were associated with higher risk of CLABSI (adjHR = 3.27, 95% CI 2.38-4.49) compared with PICCs. CONCLUSIONS: PICCs have a protective role and the effect of fluctuation curve feature in CLABSI when compared to CVCs, and the first 8 calendar days after CVC insertion are the acute stage of CVC-associated BSI.

Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism.

BACKGROUND: FGF8-FGFR1 signalling is involved in multiple biological processes, while impairment of this signalling is one of the main reasons for isolated hypogonadotropic hypogonadism (IHH). Recently, several negative modulators of FGF8-FGFR1 signalling were also found to be involved in IHH, including DUSP6, IL17RD, SPRY2 and SPRY4. The aim of this study was to investigate the genotypic and phenotypic spectra of these genes in a large cohort of Chinese patients with IHH. METHODS: A total of 196 patients with IHH were enrolled in this study. Whole-exome sequencing was performed to identify variants, which was verified by PCR and Sanger sequencing. RESULTS: Four heterozygous DUSP6 variants (p.S157I, p.R83Q, p.P188L and p.N355I) were found in six patients. Cryptorchidism, dental agenesis, syndactyly and blue colour blindness were commonly observed in patients with DUSP6 mutations. Six heterozygous IL17RD variants (p.P191L, p.G35V, p.S671L, p.A221T, p.I329M and p.I329V) were found in seven patients. Segregation analysis indicated that 100% (5/5) of probands inherited the IL17RD variants from their unaffected parents, and oligogenicity was found in 4/7 patients. One rare SPRY4 variant (p.T68S) was found in a female patient with Kallmann syndrome who also carried a PLXNA1 mutation. CONCLUSION: Our study greatly enriched the genotypic and phenotypic spectra of DUSP6, IL17RD and SPRY4 in IHH. Mutations in DUSP6 alone seem sufficient to cause IHH in an autosomal dominant manner, whereas IL17RD or SPRY4 mutations may cause IHH phenotypes in synergy with variants in other IHH-associated genes.

Age-Related Changes in the Composition of Intestinal Microbiota in Elderly Chinese Individuals.

INTRODUCTION: Intestinal microbiota affects human health and aging. The composition of intestinal microbiota and inflammation indices in elderly Chinese, especially centenarians, is unclear. OBJECTIVE: This study aimed to explore the relationships between intestinal microbiota and inflammation in healthy housebound elders in Shanghai, China. METHODS: We enrolled 156 differently aged adults and assigned them into 4 groups: those aged 35-64 years were assigned into Group AD; 65-79 years into Group YO; 80-94 years into Group MO; and 95-102 years into Group VO. RESULTS: The diversity of intestinal microbiota in Group VO was significantly reduced compared with that of the other 3 groups. Bacteroidetes abundance in Group VO was significantly lower than that in Groups AD, YO, or MO; Proteobacteria abundance showed the opposite trend. Akkermansia, Bifidobacterium, and Lactobacillus abundance in Group VO was significantly higher than that in the other 3 groups; Anaerostipes, Butyricicoccus, and Faecalibacterium abundance showed the opposite trend. Solobacterium abundance in Group VO was significantly lower than that in the other 3 groups; Campylobacter, Porphyromonas, Escherichia, and Pseudomonas abundance showed the opposite trend. Plasma levels of tumor necrosis factor-α (TNF-α), IL-6, and IL-8 in Group VO were significantly higher than those in Groups AD, YO, and MO, while those in Group MO were significantly higher than those in Groups AD and YO. IL-1ß and IL-10 plasma levels were not significantly different among the 4 groups. Proteobacteria abundance was positively correlated with TNF-α and IL-8 levels, while Campylobacter abundance was positively correlated with those of TNF-α and IL-6. Anaerostipes and Faecalibacterium abundance was negatively correlated with TNF-α and IL-6 levels. CONCLUSIONS: The diversity of intestinal microbiota in the oldest participants (centenarians) decreased significantly, with several beneficial bacterial strains showing increased or decreased abundance; harmful bacterial species showed a similar trend. Our oldest participants (centenarians) demonstrated significantly increased levels of pro-inflammatory cytokines, which may be related to inflammaging.

Chronic exposure to deltamethrin disrupts intestinal health and intestinal microbiota in juvenile crucian carp.

The indiscriminate use of deltamethrin in agriculture and aquaculture can lead to residues increased in many regions, which poses negative impacts on intestinal health of aquatic organisms. Although the potential toxicity of deltamethrin have recently attracted attention, the comprehensive studies on intestinal injuries after chronic deltamethrin exposure remain poorly understood. Herein, in a 28-day chronic toxicity test, crucian carp expose to different concentrations of deltamethrin (0, 0.3, and 0.6 µg/L) were used as the research object. We found that the morphology changes and increased goblet cells in intestinal tissue, and the extent of tissue injury increased along with the increasing exposure dose of deltamethrin. Additionally, the genes expression of antioxidant activity (Cu/Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase 1 (GPX1), and catalase (CAT)), inflammatory response (tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin 1 beta (IL-1ß)), and tight junctions (Claudin 12 (CLDN12), and tight junction protein 1 (ZO-1)) dramatically increased. Meanwhile, the apoptosis and autophagy process were triggered through caspase-9 cascade and autophagy related 5 (ATG5)- autophagy related 12 (ATG12) conjugate. Besides, chronic deltamethrin exposure increased the amount of Proteobacteria and Verrucomicrobiota, while decreased Fusobacteriota abundance, resulting in intestinal microbiota function disorders. In summary, our results highlight that chronic exposure to deltamethrin cause serious intestinal toxicity and results in physiological changes and intestinal flora disturbances.