Multi-omic analysis reveals the effects of interspecific hybridization on the synthesis of seed reserve polymers in a Triticum turgidum ssp. durum × Aegilops sharonensis amphidiploid.

BACKGROUND: Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing quality of wheat flour. Polyploidization results in duplicated chromosomes, and the genomes are often unstable and may result in a large number of gene losses and gene rearrangements. However, the instability of the genome itself, as well as the large number of duplicated genes generated during polyploidy, is an important driving force for genetic innovation. In this study, we compared the differences in starch and SSP, and analyzed the transcriptome and metabolome among Aegilops sharonensis (R7), durum wheat (Z636) and amphidiploid (Z636×R7) to reveal the effects of polyploidization on the synthesis of seed reserve polymers. RESULTS: The total starch and amylose content of Z636×R7 was significantly higher than R7 and lower than Z636. The gliadin and glutenin contents of Z636×R7 were higher than those in Z636 and R7. Through transcriptome analysis, there were 21,037, 2197, 15,090 differentially expressed genes (DEGs) in the three comparison groups of R7 vs Z636, Z636 vs Z636×R7, and Z636×R7 vs R7, respectively, which were mainly enriched in carbon metabolism and amino acid biosynthesis pathways. Transcriptome data and qRT-PCR were combined to analyze the expression levels of genes related to storage polymers. It was found that the expression levels of some starch synthase genes, namely AGP-L, AGP-S and GBSSI in Z636×R7 were higher than in R7 and among the 17 DEGs related to storage proteins, the expression levels of 14 genes in R7 were lower than those in Z636 and Z636×R7. According to the classification analysis of all differential metabolites, most belonged to carboxylic acids and derivatives, and fatty acyls were enriched in the biosynthesis of unsaturated fatty acids, niacin and nicotinamide metabolism, one-carbon pool by folate, etc. CONCLUSION: After allopolyploidization, the expression of genes related to starch synthesis was down-regulated in Z636×R7, and the process of starch synthesis was inhibited, resulting in delayed starch accumulation and prolongation of the seed development process. Therefore, at the same development time point, the starch accumulation of Z636×R7 lagged behind that of Z636. In this study, the expression of the GSe2 gene in Z636×R7 was higher than that of the two parents, which was beneficial to protein synthesis, and increased the protein content. These results eventually led to changes in the synthesis of seed reserve polymers. The current study provided a basis for a greater in-depth understanding of the mechanism of wheat allopolyploid formation and its stable preservation, and also promoted the effective exploitation of high-value alleles.

Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Nintedanib ameliorates osteoarthritis in mice by inhibiting synovial inflammation and fibrosis caused by M1 polarization of synovial macrophages via the MAPK/PI3K-AKT pathway.

Synovial inflammation and fibrosis are important pathological changes associated with osteoarthritis (OA). Herein, we investigated if nintedanib, a drug specific for pulmonary fibrosis, plays a positive role in osteoarthritic synovial inflammation and fibrosis. We assessed the effect of nintedanib on osteoarthritic synovial inflammation and fibrosis in a mouse model of OA created by destabilization of the medial meniscus and a macrophage M1 polarization model created by stimulating RAW264.7 cells with lipopolysaccharide. Histological staining showed that daily gavage administration of nintedanib significantly alleviated articular cartilage degeneration, reduced the OARSI score, upregulated matrix metalloproteinase-13 and downregulated collagen II expression, and significantly reduced the synovial score and synovial fibrosis in a mouse OA model. In addition, immunofluorescence staining showed that nintedanib significantly decreased the number of M1 macrophages in the synovium of a mouse model of OA. In vitro results showed that nintedanib downregulated the phosphorylation levels of ERK, JNK, p38, PI3K, and AKT while inhibiting the expression of macrophage M1 polarization marker proteins (CD86, CD80, and iNOS). In conclusion, this study suggests that nintedanib is a potential candidate for OA treatment. The mechanisms of action of nintedanib include the inhibition of M1 polarization in OA synovial macrophages via the MAPK/PI3K-AKT pathway, inhibition of synovial inflammation and fibrosis, and reduction of articular cartilage degeneration.

Predictive value of Global Leadership Initiative on Malnutrition criteria combined with handgrip strength for postoperative outcomes in overweight colorectal cancer patients.

BACKGROUND AND AIM: The Global Leadership Initiative on Malnutrition (GLIM) criteria are increasingly used to assess the nutritional status of hospitalized patients and predict the prognosis of patients with malignant tumors; however, malnutrition is often overlooked in overweight individuals, such as colorectal cancer patients. This study aimed to investigate the predictive value of the GLIM criteria combined with handgrip strength (HGS) in overweight colorectal cancer patients. METHODS: This retrospective study enrolled overweight patients who underwent radical resection for colorectal cancer at two centers between 2015 and 2021. Malnutrition was diagnosed based on the GLIM criteria. Skeletal muscle mass was assessed using the skeletal muscle index, and skeletal muscle function was assessed using the HGS test. The risk factors for complications and survival were also evaluated. RESULTS: A total of 850 patients were enrolled in the study. The incidence of malnutrition in the GLIM and HGS-GLIM groups was 12.4% and 6.4%, respectively. The incidence of total complications in both the malnutrition groups was significantly higher than that in the control group. Patients in the HGS-GLIM-malnutrition group had worse overall survival and disease-free survival. HGS-GLIM was independently associated with postoperative complications (P = 0.046), overall survival (P = 0.037), and disease-free survival (P = 0.047). CONCLUSION: The GLIM criteria combined with the HGS test is an effective tool for diagnosing malnutrition. Particularly, these modalities are applicable in overweight colorectal cancer patients. Compared with the standard GLIM criteria, this tool has a better predictive value for postoperative complications and long-term survival.

Association between social capital and utilization of essential public health services among elderly migrants: a multilevel logistic study based on the 2017 China migrant dynamic survey (CMDS).

BACKGROUND: As the number of elderly migrants in China continues to grow, it is necessary to pay closer attention to their health and health services. Some studies have confirmed that social capital plays a significant role in the utilization of health services. Therefore, an in-depth exploration of the relationship between social capital and the utilization of essential public health services (EPHS) by elderly migrants will not only contribute to improving their overall health but also facilitate a more balanced development of public health service system in China. METHODS: Based on the cross-sectional data from the 2017 China Migrants Dynamic Survey (CMDS), this study examined the impact of social capital on the utilization of EPHS among elderly migrants. We evaluated social capital at two distinct levels: the individual and the community, and considered two dimensions of social capital: structural social capital (SSC) and cognitive social capital (CSC). The study aimed to delve into the impact of these forms of social capital on the utilization of EPHS among elderly migrants, and whether the migration range moderates this impact by multilevel logistic regression analysis. RESULTS: A total of 5,728 migrant elderly individuals were selected. The health records establishment rate and health education acceptance rate were approximately 33.0% and 58.6%, respectively. Social capital influenceed the utilization of EPHS among elderly migrants. Specifically, individual-level SSC and CSC have impacts on both the establishment of health records (OR = 1.598, 95%CI 1.366-1.869; OR = 1.705, 95%CI 1.433-2.028) and the acceptance of health education (OR = 1.345, 95%CI 1.154-1.567; OR = 2.297, 95%CI 1.906-2.768) among elderly migrants, while community-level SSC only affected the acceptance of health education (OR = 3.838, 95%CI 1.328-11.097). There were significant differences in individual-level SSC, health records, and health education among different migration range subgroups among elderly migrants. Migration range moderated the effect of social capital on the utilization of EPHS, crossing provinces could weaken the relationship between SSC and health education. CONCLUSIONS: Social capital is associated with a higher utilization rate of EPHS among elderly migrants. It is necessary to encourage them to actively participate in social activities, strengthen public services and infrastructure construction in the area, and improve their sense of belonging and identity.

A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

The Feasibility and Accuracy of Holographic Navigation with Laser Crosshair Simulator Registration on a Mixed-Reality Display.

Addressing conventional neurosurgical navigation systems' high costs and complexity, this study explores the feasibility and accuracy of a simplified, cost-effective mixed reality navigation (MRN) system based on a laser crosshair simulator (LCS). A new automatic registration method was developed, featuring coplanar laser emitters and a recognizable target pattern. The workflow was integrated into Microsoft's HoloLens-2 for practical application. The study assessed the system's precision by utilizing life-sized 3D-printed head phantoms based on computed tomography (CT) or magnetic resonance imaging (MRI) data from 19 patients (female/male: 7/12, average age: 54.4 ± 18.5 years) with intracranial lesions. Six to seven CT/MRI-visible scalp markers were used as reference points per case. The LCS-MRN's accuracy was evaluated through landmark-based and lesion-based analyses, using metrics such as target registration error (TRE) and Dice similarity coefficient (DSC). The system demonstrated immersive capabilities for observing intracranial structures across all cases. Analysis of 124 landmarks showed a TRE of 3.0 ± 0.5 mm, consistent across various surgical positions. The DSC of 0.83 ± 0.12 correlated significantly with lesion volume (Spearman rho = 0.813, p < 0.001). Therefore, the LCS-MRN system is a viable tool for neurosurgical planning, highlighting its low user dependency, cost-efficiency, and accuracy, with prospects for future clinical application enhancements.

Variations in mitochondrial DNA coding and D-loop region are associated with early embryonic development defects in infertile women.

Mitochondrial DNA (mtDNA) plays a critical role in oocyte maturation, fertilization, and early embryonic development. Defects in mtDNA may determine the alteration of the mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply, leading to impaired oocyte maturation, abnormal fertilization, and low embryonic developmental potential, ultimately leading to female infertility. This case-control study was established to investigate the correlation between mtDNA variations and early embryonic development defects. Peripheral blood was collected for next-generation sequencing from women who suffered the repeated failures of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) cycles due to early embryonic development defects as well as in-house healthy controls, and the sequencing results were statistically analyzed for all subjects. This study found that infertile women with early embryonic development defects carried more mtDNA variants, especially in the D-loop region, ATP6 gene, and CYTB gene. By univariate logistic regression analysis, 16 mtDNA variants were associated with an increased risk of early embryonic development defects (OR > 1, p < 0.05). Furthermore, we identified 16 potentially pathogenic mtDNA variants only in infertile cases. The data proved that mtDNA variations were associated with early embryonic development defects in infertile Chinese women.

Deep regression using 99mTc-DTPA dynamic renal imaging for automatic calculation of the glomerular filtration rate.

OBJECTIVES: To develop and evaluate an artificial intelligence (AI) system that can automatically calculate the glomerular filtration rate (GFR) from dynamic renal imaging without manually delineating the regions of interest (ROIs) of kidneys and the corresponding background. METHODS: This study was a single-center retrospective analysis of the data of 14,634 patients who underwent 99mTc-DTPA dynamic renal imaging. Two systems based on convolutional neural networks (CNN) were developed and evaluated: sGFRa predicts the radioactive counts of ROIs and calculates GFR using the Gates equation and sGFRb directly predicts GFR from dynamic renal imaging without using other information. The root-mean-square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and R2 were used to evaluate the performance of our approach. RESULTS: sGFRa achieved an RMSE of 5.05, MAE of 4.03, MAPE of 6.07%, and R2 of 0.93 for total GFR while sGFRb achieved an RMSE of 7.61, MAE of 5.92, MAPE of 8.92%, and R2 of 0.85 for total GFR. The accuracy of sGFRa and sGFRb in determining the stage of chronic kidney disease was 87.41% and 82.44%, respectively. CONCLUSIONS: The findings of sGFRa show that automatic GFR calculation based on CNN and using dynamic renal imaging is feasible and efficient and, additionally, can aid clinical diagnosis. Furthermore, the promising results of sGFRb demonstrate that CNN can predict GFR from dynamic renal imaging without additional information. KEY POINTS: • Our CNN-based AI systems can automatically calculate GFR from dynamic renal imaging without manually delineating the ROIs of kidneys and the corresponding background. • sGFRa accurately predicted the radioactive counts of ROIs and calculated GFR using the Gates method. • sGFRb-predicted GFR directly without any parameters related to the Gates equation.

Confinement Effects in Carbonized ZIF-Confined Hollow PtCo Nanospheres Enable the Methanol Oxidation Reaction.

Confinement effects in highly porous nanostructures can effectively adjust the selectivity and kinetics of electrochemical reactions, which can boost the methanol oxidation reaction (MOR). In this work, carbonized ZIF-8-confined hollow PtCo nanospheres (PtCo@carbonized ZIF-8) were fabricated using a facile strategy. A monodisperse confined region was successfully prepared, and the dispersion of the PtCo nanoparticles (NPs) could be precisely regulated, allowing for the effective tuning of the confined region. Thus, the precise regulation of the catalytic reaction was achieved. Importantly, hollow PtCo NPs were prepared using a method based on the Kirkendall effect, and their forming mechanism was systematically investigated. Because of the confinement effects of carbonized zeolitic imidazolate framework-8 (ZIF-8), the crystal and electronic structures of the PtCo NPs were able to be effectively tuned. Our electrochemical results show that PtCo@carbonized ZIF-8 composites manifest a higher mass activity (1.4 A mgPt-1) and better stability compared to commercial Pt/C.

Land-Water Transport and Sources of Nitrogen Pollution Affecting the Structure and Function of Riverine Microbial Communities.

The characterization of variations in riverine microbiota that stem from contaminant sources and transport modes is important for understanding biogeochemical processes. However, the association between complex anthropogenic nitrogen pollution and bacteria has not been extensively investigated owing to the difficulties faced while determining the distribution of nitrogen contaminants in watersheds. Here, we employed the Soil and Water Assessment Tool alongside microbiological analysis to explore microbial characteristics and their responses to complex nitrogen pollution patterns. Significant variations in microbial communities were observed in sub-basins with distinct land-water pollution transport modes. Point source-dominated areas (PSDAs) exhibited reduced microbial diversity, high number of denitrification groups, and increased nitrogen cycling compared with others. The negative relative deviations (-3.38) between the measured and simulated nitrate concentrations in PSDAs indicated that nitrate removal was more effective in PSDAs. Pollution sources were also closely associated with microbiota. Effluents from concentrated animal feeding operations were the primary factors relating to the microbiota compositions in PSDAs and balanced areas. In nonpoint source-dominated areas, contaminants from septic tanks become the most relevant sources to microbial community structures. Overall, this study expands our knowledge regarding microbial biogeochemistry in catchments and beyond by linking specific nitrogen pollution scenarios to microorganisms.

ZIC2 promotes colorectal cancer growth and metastasis through the TGF-ß signaling pathway.

ZIC2 is involved in the tumor progression of many types of cancers. The role of ZIC2 in the metastasis of colorectal cancer and its mechanism are not yet clear. In this study, we found that high ZIC2 expression was not only associated with poor prognosis, relapse-free survival and advanced metastasis but was also an independent prognostic factor in colorectal cancer patients. Moreover, ZIC2 knockdown inhibited cell proliferation, migration and invasion, while the upregulation of ZIC2 had the opposite effect in vitro. ZIC2 overexpression induced TGF-ß1 expression and increased Smad3 phosphorylation. The carcinogenic effects of elevated ZIC2 expression can be eliminated by interfering with the TGF-ß1 receptor with inhibitors. This further verified the promoting effect of ZIC2 on the TGF-ß signaling pathway. In vivo experiments have also confirmed that ZIC2 can promote liver metastases of colorectal cancer. The results suggest that ZIC2 is associated with poor prognosis and relapse-free survival in colorectal cancer patients. Moreover, ZIC2 promoted colorectal cancer progression and metastasis by activating the TGF-ß signaling pathway. Hence, ZIC2 is expected to be a new therapeutic and prognostic target for colorectal cancer in the future.

Dual-wavelength off-axis digital holography in ImageJ: toward real-time phase retrieval using CUDA streams.

An ImageJ plug-in is developed to realize automatic real-time phase reconstruction for dual-wavelength digital holography (DH). This plug-in assembles the algorithms, including automatic phase reconstruction based on the division algorithm and post-processing. These algorithms are implemented and analyzed using a CPU and GPU, respectively. To hide the CPU-to-GPU data transfer latency, an optimization scheme using Compute Unified Device Architecture (CUDA) streams is proposed in ImageJ. Experimental results show that the proposed plug-in can perform faster reconstruction for dual-wavelength DH, resulting in frame rates up to 48 fps even for one-megapixel digital holograms on a normal PC. In other words, the proposed plug-in can realize real-time phase reconstruction for dual-wavelength digital holographic videos.

The Association between Serum Chemerin and Peritoneal Membrane Transport Function in Patients Undergoing Incident Peritoneal Dialysis: A Prospective Cohort Study.

INTRODUCTION: Some biomarkers in drained dialyzate or peritoneal membrane have been found related to the dialyzate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays important roles in inflammation, adipogenesis, and metabolism. We intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients. METHODS: This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test after PD for 4-6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay. The patients' CVDs were recorded during the follow-up period. RESULTS: 151 eligible patients with a mean age of 46.59 ± 13.52 years were enrolled, and the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 ng/mL vs. 27.37 ng/mL, p = 0.000), and there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42 vs. 21%, p = 0.009). CONCLUSIONS: Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of the peritoneal membrane, and serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.

LncRNA HIF1A-AS2 mediates imatinib resistance by regulating autophagy in gastrointestinal stromal tumor cells.

The aim of this study was to explore the role and mechanism of long non-coding RNA (lncRNA) HIF1A antisense RNA 2 (HIF1A-AS2) in regulating imatinib (IM) resistance in gastrointestinal stromal tumor (GIST) cells under hypoxia. The expression of HIF1A-AS2 was silenced by siRNA in GIST cells. Cytotoxicity, apoptosis, and autophagy were evaluated under normoxic and hypoxic conditions. The expression levels of HIF1A-AS2, HIF1A, apoptosis-associated genes, and autophagy-associated genes were determined by qRT-PCR analysis and western blot. We found that lncRNA HIF1A-AS2 was highly expressed in GIST tissues and cells. Knockdown of HIF1A-AS2 increased the sensitivity of GIST cells to IM and increased apoptosis. Moreover, a hypoxic environment decreased the sensitivity of GIST cells to IM, and the knockdown of HIF1A-AS2 reversed this effect. Mechanistically, the knockdown of HIF1A-AS2 inhibited IM-mediated autophagy. Finally, HIF1A was found to positively regulate HIF1A-AS2 under hypoxic conditions. Collectively, these data demonstrate that hypoxia-induced HIF1A-AS2 promotes IM resistance in GIST cells by regulating autophagy.

Structural basis for RNA recognition by the N-terminal tandem RRM domains of human RBM45.

RBM45 is an RNA-binding protein involved in neural development, whose aggregation is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). However, the mechanisms of RNA-binding and aggregation of RBM45 remain unelucidated. Here, we report the crystal structure of the N-terminal tandem RRM domains of human RBM45 in complex with single-stranded DNA (ssDNA). Our structural and biochemical results revealed that both the RRM1 and RRM2 of RBM45 recognized the GAC sequence of RNA/ssDNA. Two aromatic residues and an arginine residue in each RRM were critical for RNA-binding, and the interdomain linker was also involved in RNA-binding. Two RRMs formed a pair of antiparallel RNA-binding sites, indicating that the N-terminal tandem RRM domains of RBM45 bound separate GAC motifs in one RNA strand or GAC motifs in different RNA strands. Our findings will be helpful in the identification of physiologic targets of RBM45 and provide evidence for understanding the physiologic and pathologic functions of RBM45.

Pseudomonas aeruginosa lasR mutant fitness in microoxia is supported by an Anr-regulated oxygen-binding hemerythrin.

Pseudomonas aeruginosa strains with loss-of-function mutations in the transcription factor LasR are frequently encountered in the clinic and the environment. Among the characteristics common to LasR-defective (LasR-) strains is increased activity of the transcription factor Anr, relative to their LasR+ counterparts, in low-oxygen conditions. One of the Anr-regulated genes found to be highly induced in LasR- strains was PA14_42860 (PA1673), which we named mhr for microoxic hemerythrin. Purified P. aeruginosa Mhr protein contained the predicted di-iron center and bound molecular oxygen with an apparent Kd of ∼1 µM. Both Anr and Mhr were necessary for fitness in lasR+ and lasR mutant strains in colony biofilms grown in microoxic conditions, and the effects were more striking in the lasR mutant. Among genes in the Anr regulon, mhr was most closely coregulated with the Anr-controlled high-affinity cytochrome c oxidase genes. In the absence of high-affinity cytochrome c oxidases, deletion of mhr no longer caused a fitness disadvantage, suggesting that Mhr works in concert with microoxic respiration. We demonstrate that Anr and Mhr contribute to LasR- strain fitness even in biofilms grown in normoxic conditions. Furthermore, metabolomics data indicate that, in a lasR mutant, expression of Anr-regulated mhr leads to differences in metabolism in cells grown on lysogeny broth or artificial sputum medium. We propose that increased Anr activity leads to higher levels of the oxygen-binding protein Mhr, which confers an advantage to lasR mutants in microoxic conditions.

Application effect of head-mounted mixed reality device combined with 3D printing model in neurosurgery ventricular and hematoma puncture training.

BACKGROUND: The purpose of this study was to explore the applicability of application effect of head-mounted mixed reality (MR) equipment combined with a three-dimensional (3D) printed model in neurosurgical ventricular and haematoma puncture training. METHODS: Digital Imaging and Communications in Medicine (DICOM) format image data of two patients with common neurosurgical diseases (hydrocephalus and basal ganglia haemorrhage) were imported into 3D Slicer software for 3D reconstruction, saved, and printed using 3D printing to produce a 1:1-sized head model with real person characteristics. The required model (brain ventricle, haematoma, puncture path, etc.) was constructed and imported into the head-mounted MR device, HoloLens, and a risk-free, visual, and repeatable system was designed for the training of junior physicians. A total of 16 junior physicians who studied under this specialty from September 2020 to March 2022 were selected as the research participants, and the applicability of the equipment and model during training was evaluated with assessment score sheets and questionnaires after training. RESULTS: According to results of the assessment and questionnaire, the doctors trained by this system are more familiar with the localization of the lateral anterior ventricle horn puncture and the common endoscopic surgery for basal ganglia haemorrhage, as well as more confident in the mastery of these two operations than the traditional training methods. CONCLUSIONS: The use of head-mounted MR equipment combined with 3D printing models can provide an ideal platform for the operation training of young doctors. Through holographic images created from the combination of virtual and real images, operators can be better immersed in the operation process and deepen their understanding of the operation and related anatomical structures. The 3D printed model can be repeatedly reproduced so that doctors can master the technology, learn from mistakes, better achieve the purpose of teaching and training, and improve the effect of training.

A High-Fat Diet Increases the Characteristics of Gut Microbial Composition and the Intestinal Damage Associated with Non-Alcoholic Fatty Liver Disease.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing annually, and emerging evidence suggests that the gut microbiota plays a causative role in the development of NAFLD. However, the role of gut microbiota in the development of NAFLD remains unclear and warrants further investigation. Thus, C57BL/6J mice were fed a high-fat diet (HFD), and we found that the HFD significantly induced obesity and increased the accumulation of intrahepatic lipids, along with alterations in serum biochemical parameters. Moreover, it was observed that the HFD also impaired gut barrier integrity. It was revealed via 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Colidextribacter, Lachnospiraceae-NK4A136-group, Acetatifactor, and Erysipelatoclostridium. Meanwhile, it reduced the abundance of Faecalibaculum, Muribaculaceae, and Coriobacteriaceae-UCG-002. The predicted metabolic pathways suggest that HFD enhances the chemotaxis and functional activity of gut microbiota pathways associated with flagellar assembly, while also increasing the risk of intestinal pathogen colonization and inflammation. And the phosphotransferase system, streptomycin biosynthesis, and starch/sucrose metabolism exhibited decreases. These findings reveal the composition and predictive functions of the intestinal microbiome in NAFLD, further corroborating the association between gut microbiota and NAFLD while providing novel insights into its potential application in gut microbiome research for NAFLD patients.