Prediction of delayed graft function by early salivary microbiota following kidney transplantation.

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.

[Clinical and genetic analysis of a child with X-linked intellectual developmental disorder due to a novel variant of NEXMIF gene].

OBJECTIVE: To explore the genetic basis for a child featuring facial dysmorphism and intellectual disabilities. METHODS: A child who was diagnosed at Linyi People's Hospital on January 5 2023 due to "mental retardation" was selected as the study subject. Peripheral blood samples of the child and his parents, in addition with an amniotic fluid sample from the his mother were collected for the extraction of genomic DNA. Whole exome sequencing was carried out for the child, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a hemizygous c.1123dupG (p.E375Gfs*4) variant of the NEXMIF gene, for which both of his parents and the fetus were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+PS2-P+PM2-P). A healthy infant was subsequently born. CONCLUSION: The hemizygous c.1123dupG (p.E375Gfs*4) variant of the NEXMIF gene probably underlay the disease in this child. Based on his clinical phenotype and genotype, the child was ultimately diagnosed with X-linked intellectual developmental disorder-98. Above finding has also enriched the mutational spectrum of the NEXMIF gene.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

Multi-omic validation of the cuproptosis-sphingolipid metabolism network: modulating the immune landscape in osteosarcoma.

Background: The current understanding of the mechanisms by which metal ion metabolism promotes the progression and drug resistance of osteosarcoma remains incomplete. This study aims to elucidate the key roles and mechanisms of genes involved in cuproptosis-related sphingolipid metabolism (cuproptosis-SPGs) in regulating the immune landscape, tumor metastasis, and drug resistance in osteosarcoma cells. Methods: This study employed multi-omics approaches to assess the impact of cuproptosis-SPGs on the prognosis of osteosarcoma patients. Lasso regression analysis was utilized to construct a prognostic model, while multivariate regression analysis was applied to identify key core genes and generate risk coefficients for these genes, thereby calculating a risk score for each osteosarcoma patient. Patients were then stratified into high-risk and low-risk groups based on their risk scores. The ESTIMATE and CIBERSORT algorithms were used to analyze the level of immune cell infiltration within these risk groups to construct the immune landscape. Single-cell analysis was conducted to provide a more precise depiction of the expression patterns of cuproptosis-SPGs among immune cell subtypes. Finally, experiments on osteosarcoma cells were performed to validate the role of the cuproptosis-sphingolipid signaling network in regulating cell migration and apoptosis. Results: In this study, seven cuproptosis-SPGs were identified and used to construct a prognostic model for osteosarcoma patients. In addition to predicting survival, the model also demonstrated reliability in forecasting the response to chemotherapy drugs. The results showed that a high cuproptosis-sphingolipid metabolism score was closely associated with reduced CD8 T cell infiltration and indicated poor prognosis in osteosarcoma patients. Cellular functional assays revealed that cuproptosis-SPGs regulated the LC3B/ERK signaling pathway, thereby triggering cell death and impairing migration capabilities in osteosarcoma cells. Conclusion: The impact of cuproptosis-related sphingolipid metabolism on the survival and migration of osteosarcoma cells, as well as on CD8 T cell infiltration, highlights the potential of targeting copper ion metabolism as a promising strategy for osteosarcoma patients.

Accurately Computing the Interacted Volume of Molecules over Their 3D Mesh Models.

For quickly predicting the rational arrangement of catalysts and substrates, we previously proposed a method to calculate the interacted volumes of molecules over their 3D point cloud models. However, the nonuniform density in molecular point clouds may lead to incomplete contours in some slices, reducing the accuracy of the previous method. In this paper, we propose a two-step method for more accurately computing molecular interacted volumes. First, by employing a prematched mesh slicing method, we layer the 3D triangular mesh models of the electrostatic potential isosurfaces of two molecules globally, transforming the volume calculation into finding the intersecting areas in each layer. Next, by subdividing polygonal edges, we accurately identify intersecting parts within each layer, ensuring precise calculation of interacted volumes. In addition, we present a concise overview for computing intersecting areas in cases of multiple contour intersections and for improving computational efficiency by incorporating bounding boxes at three stages. Experimental results demonstrate that our method maintains high accuracy in different experimental data sets, with an average relative error of 0.16%. On the same experimental setup, our average relative error is 0.07%, which is lower than the previous algorithm's 1.73%, improving the accuracy and stability in calculating interacted volumes.

Recognition of antitussive components in Farfarae Flos based on grey relational analysis and partial least squares regression. / åŸºäºŽç°è‰²å ³è”åº¦åˆ†æžå’Œåæœ€å°äºŒä¹˜å›žå½’è¾¨è¯†æ¬¾å†¬èŠ±æ­¢å’³æ´»æ€§æˆåˆ†.

OBJECTIVES: Farfarae Flos has the effect of cough suppression and phlegm elimination, with cough suppression as the main function. Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect, and some components have been confirmed to have cough suppressant activity. However, the antitussive material basis of Farfarae Flos has not been systematically elucidated. This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography (HPLC) fingerprint of Farfarae Flos extract with its cough suppressant activity. METHODS: HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data. Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract. SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups, a positive control group, and a blank control group (12 groups in total), with 10 guinea pigs in each group. The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10 (4 g/kg), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days. The guinea pigs were placed in 5 L closed wide-mouth bottles, and 17.5% citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes. The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig. Grey relational analysis (GRA) and partial least squares regression (PLSR) were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data, and predict the group of active ingredients in Farfarae Flos with antitussive activity. The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity: SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group, an active ingredient group, a positive control group, and a blank control group (4 groups in total), with 10 guinea pigs in each group. The S9 group was administered Farfarae Flos extract S9 (4 g/kg), the active ingredient group was administered the predicted combination of antitussive active ingredients (dose equivalent to 4 g/kg of Farfarae Flos extract S9), the positive control group was administered pentoverine citrate (10 mg/kg), and the blank control group was administered purified water. Each group received continuous oral administration for 5 days, and animal modeling and observation of efficacy indicators were the same as above. RESULTS: The HPLC fingerprint of 10 batches of Farfarae Flos extract was established, and the peak area data of 14 main common peaks were obtained. The antitussive effect data of 10 batches of Farfarae Flos extract were obtained. Compared with the blank control group, the cough latence in the positive control group and S1, S2, S3, S4, S6, S7, S8, S9, S10 groups was prolonged (all P<0.01), while the cough frequency in 5 minutes in the positive control group and S1, S2, S4, S6, S8, S9, S10 groups was decreased (all P<0.05). The analysis of spectrum-effect relationship revealed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercitrin, and rutin had high contribution to the antitussive effect of Farfarae Flos, and the 6 components were predicted to be the antitussive component group of Farfarae Flos. The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05), which confirmed that isochlorogenic acid C, isochlorogenic acid A, chlorogenic acid, isochlorogenic acid B, isoquercetin, and rutin were the antitussive component group of Farfarae Flos. CONCLUSIONS: The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos. The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Additional yield of random biopsy in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: There is limited clinical data regarding the additional yields of random biopsies during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for IBD patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis, and 16.20% in per-lesion analysis. The detection rate were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full HD equipment should consider incorporating RB in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.

Perioperative impact of liver cirrhosis on robotic liver resection for hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: The safety and efficacy of robotic liver resection (RLR) for patients with hepatocellular carcinoma (HCC) have been reported worldwide. However, the exact role of RLR in HCC patients with liver cirrhosis is not sufficiently determined. METHODS: We conducted a retrospective study on consecutive patients with cirrhosis or non-cirrhosis who received RLR for HCC from 2018 to 2023. Data on patients' demographics and perioperative outcomes were collected and analyzed. Propensity score matching (PSM) analysis was performed. Multivariate logistic regression analysis was performed to determine the risk factors of prolonged postoperative length of stay (LOS) and morbidity. RESULTS: Of the 571 patients included, 364 (64%) had cirrhosis. Among the cirrhotic patients, 48 (13%) were classified as Child-Pugh B. After PSM, the cirrhosis and non-cirrhosis group (n = 183) had similar operative time, estimated blood loss, postoperative blood transfusion, LOS, overall morbidity (p > 0.05). In addition, the intraoperative and postoperative outcomes were similar between the two groups in the subgroup analyses of patients with tumor size ≥ 5 cm, major hepatectomy, and high/expert IWATE difficulty grade. However, patients with Child-Pugh B cirrhosis had longer LOS and more overall morbidity than that of Child-Pugh A. Child-Pugh B cirrhosis, ASA score > 2, longer operative time, and multiple tumors were risk factors of prolonged LOS or morbidity in patients with cirrhosis. CONCLUSION: The presence of Child-Pugh A cirrhosis didn't significantly influence the difficulty and perioperative outcomes of RLR for selected patients with HCC. However, even in high-volume center, Child-Pugh B cirrhosis was a risk factor for poor postoperative outcomes.

A MELET- and IFE-based UV-visible luminescent ratiometric probe for quantization of mercury(II) and nitrofurantoin in environmental sewage.

A novel fluorimetric ratiometric probe of green and eco-friendily nitrogen-enriched, oxygen-doped carbon nanodots (Cnanodots) was prepared for the quantitative analysis of mercury(II) (HgII) and nitrofurantoin (Nit) in the environmental sewage. The Cnanodots exhibits dual-emission peaks respectively at 345 and 445 nm under 285 nm excitation, with excitation-independent properties. Unexpectedly, this Cnanodots displays two obvious ratiometric responses to HgII and Nit through decreasing the signal at 345 nm and remaining invariable at 445 nm. Experimental results confirm that the highly sensitive analysis of HgII and Nit are achieved respectively based on matching energy-level electron transfer and inner filter effect mechanisms. The fluorescence (FL) ratiometric intensity of [FL345nm/FL445nm] expresses a good linear relationship with the concentration of HgII in the scope of 0.01-20 µM, while the logarithm of [Log(FL0345nm-FL345nm)] on the quenching degree of the probe by Nit also shows a good linear correlation within the range of 0.01-100 µM. The detection limits were calculated to be 4.14 nM for HgII, and 7.84 nM for Nit. Moreover, recovery experiments of Cnanodots for HgII and Nit sensing in real sewage samples obtained satisfactory results, comfirming the feasibility of practical application.

An unenhanced 3D-FLAIR sequence using long repetition time and constant flip angle to image endolymphatic hydrops.

OBJECTIVES: To evaluate a three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence using a long repetition time (TR) and constant flip angle (CFA) in differentiating between perilymph and endolymph in a phantom study, and unenhanced endolymphatic hydrops (EH) imaging in a patient study. METHODS: Three solutions in similar ion and protein concentrations with endolymph, perilymph, and cerebrospinal fluid were prepared for variable flip angle (VFA) 3D-FLAIR (TR 10,000 ms) and CFA (120°) 3D-FLAIR using different TR (10,000, 16,000, and 20,000 ms). Fifty-two patients with probable or definite Meniere's disease received unenhanced CFA (120°) 3D-FLAIR using a long TR (20,000 ms) and 4-h-delay enhanced CFA (120°) 3D-FLAIR (TR 16,000 ms). Image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of them were compared. Agreement in the evaluation of the EH degree between them was analyzed. RESULTS: In the phantom study, CNRs between perilymphatic and endolymphatic samples of VFA 3D-FLAIR (TR 10,000 ms) and CFA 3D-FLAIR (TR 10,000, 16,000, and 20,000 ms) were 6.66 ± 1.30, 17.90 ± 2.76, 23.87 ± 3.09, and 28.22 ± 3.15 (p < 0.001). In patient study, average score (3.65 ± 0.48 vs. 4.19 ± 0.40), SNR (34.56 ± 9.80 vs. 51.40 ± 11.27), and CNR (30.66 ± 10.55 vs. 45.08 ± 12.27) of unenhanced 3D-FLAIR were lower than enhanced 3D-FLAIR (p < 0.001). Evaluations of the two sequences showed excellent agreement in the cochlear and vestibule (Kappa value: 0.898 and 0.909). CONCLUSIONS: The CFA 3D-FLAIR sequence using a long TR could be used in unenhanced EH imaging with high accuracy. CLINICAL RELEVANCE STATEMENT: Unenhanced imaging of endolymphatic hydrops is valuable in the diagnosis and follow-up of patients, especially those who cannot receive contrast-enhanced MRI. KEY POINTS: Ion and protein concentration differences can be utilized in differentiating endolymph and perilymph on MRI. Endolymphatic and perilymphatic samples could be differentiated in vitro on this 3D-FLAIR sequence. This unenhanced 3D-FLAIR sequence is in excellent agreement with the enhanced constant flip angle 3D-FLAIR sequence.

Passive hyperthermia alters the resting-state functional connectivity of mouse brain.

PURPOSE: To investigate how passive hyperthermia affect the resting-state functional brain activity based on an acute mouse model after heat stress exposure. MATERIALS AND METHODS: Twenty-eight rs-fMRI data of C57BL/6J male mice which weighing about 24 ∼ 29 g and aged 12 ∼ 16 weeks were collected. The mice in the hyperthermia group (HT, 40 °C ± 0.5 °C, 40 min) were subjected to passive hyperthermia before the anesthesia preparation for scanning. While the normal control group (NC) was subjected to normothermia condition (NC, 20 °C ± 2 °C, 40 min). After data preprocessing, we performed independent component analysis (ICA) and region of interested (ROI)-ROI functional connectivity (FC) analyses on the data of both HT (n = 13) and NC (n = 15). RESULTS: The group ICA analysis showed that the HT and the NC both included 11 intrinsic connectivity networks (ICNs), and can be divided into four types of networks: the cortical network (CN), the subcortical network (SN), the default mode network (DMN), and cerebellar networks. CN and SN belongs to sensorimotor network. Compared with NC, the functional network organization of ICNs in the HT was altered and the overall functional intensity was decreased. Furthermore, 13 ROIs were selected in CN, SN, and DMN for further ROI-ROI FC analysis. The ROI-ROI FC analysis showed that passive hyperthermia exposure significantly reduced the FC strength in the overall brain represented by CN, SN, DMN of mice. CONCLUSION: Prolonged exposure to high temperature has a greater impact on the overall perception and cognitive level of mice, which might help understand the relationship between neuronal activities and physiological thermal sensation and regulation as well as behavioral changes.

Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

High-Performance 2D Ambipolar MoTe2 Lateral Memristors by Mild Oxidation.

2D transition metal dichalcogenides (TMDCs) have been intensively explored in memristors for brain-inspired computing. Oxidation, which is usually unavoidable and harmful in 2D TMDCs, could also be used to enhance their memristive performances. However, it is still unclear how oxidation affects the resistive switching behaviors of 2D ambipolar TMDCs. In this work, a mild oxidation strategy is developed to greatly enhance the resistive switching ratio of ambipolar 2H-MoTe2 lateral memristors by more than 10 times. Such an enhancement results from the amplified doping due to O2 and H2O adsorption and the optimization of effective gate voltage distribution by mild oxidation. Moreover, the ambipolarity of 2H-MoTe2 also enables a change of resistive switching direction, which is uncommon in 2D memristors. Consequently, as an artificial synapse, the MoTe2 device exhibits a large dynamic range (≈200) and a good linearity (1.01) in long-term potentiation and depression, as well as a high-accuracy handwritten digit recognition (>96%). This work not only provides a feasible and effective way to enhance the memristive performance of 2D ambipolar materials, but also deepens the understanding of hidden mechanisms for RS behaviors in oxidized 2D materials.

Identifying the genetic mechanism of medium-low temperature fluoride-enriched geothermal groundwater by the self-organizing map and evaluating health risk in the Wugongshan area, southeast China.

Fluoride-enriched groundwater is a serious threat for groundwater supply around the world. The medium-low temperature fluoride-enriched geothermal groundwater resource is widely distributed in the circum-Wugongshan area. And the fluoride concentration of all geothermal samples exceeds the WHO permissible limit of 1.5 mg/L. The Self-Organizing Map method, hydrochemical and isotopic analysis are used to decipher the driving factors and genetic mechanism of fluoride-enriched geothermal groundwater. A total of 19 samples collected from the circum-Wugongshan geothermal belt are divided into four clusters by the self-organizing map. Cluster I, Cluster II, Cluster III, and Cluster IV represent the geothermal groundwater with the different degree of fluoride concentration pollution, the different hydrochemical type, and the physicochemical characteristic. The high F- concentration geothermal groundwater is characterized by HCO3-Na with alkalinity environment. The δD and δ18O values indicate that the geothermal groundwater origins from the atmospheric precipitation with the recharge elevation of 1000-2100 m. The dissolution of fluoride-bearing minerals is the main source of fluoride ions in geothermal water. Moreover, groundwater fluoride enrichment is also facilitated by water-rock interaction, cation exchange and alkaline environment. Additionally, the health risk assessment result reveals that the fluorine-enriched geothermal groundwater in the western part of Wugongshan area poses a more serious threat to human health than that of eastern part. The fluoride health risks of geothermal groundwater for different group show differentiation, 100% for children, 94.74% for adult females, and 68.42% for adult males, respectively. Compared with adult females and adult males, children faced the greatest health risks. The results of this study provide scientific evaluation for the utilization of geothermal groundwater and the protection of human health around the Wugongshan area.

Autologous Tissue Repair and Total Face Restoration.

Importance: Total face restoration remains a challenge in modern reconstructive surgery. After 17 years of experiments and preliminary clinical studies, a new concept of face prefabrication was developed for face restoration with autologous tissue. Objective: To evaluate the long-term results of face restoration with autologous tissue and report a finalized and standardized approach of face prefabrication. Design, Setting, and Participants: In this single-center long-term retrospective study, 32 patients who underwent total face restoration between 2005 and 2022 were reviewed. These patients underwent total facial reconstruction, which included flap prefabrication, 3-dimensional printing, tissue expansion, and flap transfer with aid of indocyanine green angiography (IGA). The flap first undergoes prefabrication by transferring vascularized fascia under the skin of the selected chest. A tissue expander is then placed under the fascia to create a large, thin, reliable skin flap after expansion. Once completed, the flap is transferred to the face during the second stage of the reconstruction. Intraoperative IGA is performed to guide the design of subsequent openings for facial fissures. Data were analyzed from July to September 2023. Main Outcomes and Measures: Flap healing, reconstructive outcome, and patient recovery were assessed during follow-up. Three questionnaires, including the 36-Item Short Form Health Survey (SF-36), Aesthetic and Functional Status Score of Facial Soft-Tissue Deformities/Defects, and the EuroQoL Health-Related Quality of Life (EQ-5D-5L), were used to evaluate the quality of life and satisfaction with facial aesthetic and functional status. Results: Of 24 included patients, 14 (58%) were male, and the mean (range) age was 32.9 (8-62) years. The mean (range) follow-up was 5.6 (2-12) years. All patients reported a significant improvement in quality of life (SF-36), especially in mean (SD) social functioning (preoperative score, 53.65 [34.51]; postoperative score, 80.73 [19.10]) and emotional stability (preoperative score, 56.67 [25.55]; postoperative score, 71.17 [18.51]). A total of 22 patients (92%) went back to work. Mean (SD) facial aesthetic status (preoperative score, 4.96 [3.26]; postoperative score, 11.52 [3.49]; P < .001) and functional status (preoperative score, 11.09 [3.51]; postoperative score, 15.78 [3.26]; P < .001) also improved. In addition, there was a significant increase in overall satisfaction and self-reported health status (preoperative score, 8.13 [1.52]; postoperative score, 3.58 [2.31]). Conclusions and Relevance: In this study, 5-year follow-up results suggested that this innovative approach to total face restoration offered a safe and valid option for indicated patients, with acceptable reconstructive and cosmetic outcomes.

Aflatoxin B1 as a complicit in intestinal damage caused by Eimeria ovinoidalis in lambs: Novel insights to reveal parasite-gut battle.

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia.

Controlled Fabrication of Metallic MoO2 Nanosheets towards High-Performance p-Type 2D Transistors.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDCs) are extensively employed as channel materials in advanced electronic devices. The electrical contacts between electrodes and 2D semiconductors play a crucial role in the development of high-performance transistors. While numerous strategies for electrode interface engineering have been proposed to enhance the performance of n-type 2D transistors, upgrading p-type ones in a similar manner remains a challenge. In this work, significant improvements in a p-type WSe2 transistor are demonstrated by utilizing metallic MoO2 nanosheets as the electrode contact, which are controllably fabricated through physical vapor deposition and subsequent annealing. The MoO2 nanosheets exhibit an exceptional electrical conductivity of 8.4 × 104 S m‒1 and a breakdown current density of 3.3 × 106 A cm‒2. The work function of MoO2 nanosheets is determined to be ≈5.1 eV, making them suitable for contacting p-type 2D semiconductors. Employing MoO2 nanosheets as the electrode contact in WSe2 transistors results in a notable increase in the field-effect mobility to 92.0 cm2 V‒1 s‒1, which is one order of magnitude higher than the counterpart devices with conventional electrodes. This study not only introduces an intriguing 2D metal oxide to improve the electrical contact in p-type 2D transistors, but also offers an effective approach to fabricating all-2D devices.