A shock flash breaking out of a dusty red supergiant.

Shock-breakout emission is light that arises when a shockwave, generated by the core-collapse explosion of a massive star, passes through its outer envelope. Hitherto, the earliest detection of such a signal was at several hours after the explosion1, although a few others had been reported2-7. The temporal evolution of early light curves should provide insights into the shock propagation, including explosion asymmetry and environment in the vicinity, but this has been hampered by the lack of multiwavelength observations. Here we report the instant multiband observations of a type II supernova (SN 2023ixf) in the galaxy M101 (at a distance of 6.85 ± 0.15 Mpc; ref. 8), beginning at about 1.4 h after the explosion. The exploding star was a red supergiant with a radius of about 440 solar radii. The light curves evolved rapidly, on timescales of 1-2 h, and appeared unusually fainter and redder than predicted by the models9-11 within the first few hours, which we attribute to an optically thick dust shell before it was disrupted by the shockwave. We infer that the breakout and perhaps the distribution of the surrounding dust were not spherically symmetric.

Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders.

The discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into autism spectrum disorder (ASD) and facilitate early diagnosis. We characterized metabolomic profiles in ASD using plasma samples collected in the Norwegian Autism Birth Cohort from mothers at weeks 17-21 gestation (maternal mid-gestation, MMG, n = 408) and from children on the day of birth (cord blood, CB, n = 418). We analyzed associations using sex-stratified adjusted logistic regression models with Bayesian analyses. Chemical enrichment analyses (ChemRICH) were performed to determine altered chemical clusters. We also employed machine learning algorithms to assess the utility of metabolomics as ASD biomarkers. We identified ASD associations with a variety of chemical compounds including arachidonic acid, glutamate, and glutamine, and metabolite clusters including hydroxy eicospentaenoic acids, phosphatidylcholines, and ceramides in MMG and CB plasma that are consistent with inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Girls with ASD have disruption of ether/non-ether phospholipid balance in the MMG plasma that is similar to that found in other neurodevelopmental disorders. ASD boys in the CB analyses had the highest number of dysregulated chemical clusters. Machine learning classifiers distinguished ASD cases from controls with area under the receiver operating characteristic (AUROC) values ranging from 0.710 to 0.853. Predictive performance was better in CB analyses than in MMG. These findings may provide new insights into the sex-specific differences in ASD and have implications for discovery of biomarkers that may enable early detection and intervention.

New insights into molecular mechanisms underlying malignant transformation of endometriosis: BANCR promotes miR-612/CPNE3 pathway activity.

RESEARCH QUESTION: Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miR-612/CPNE3 pathway? DESIGN: The expression patterns of BANCR, miR-612 and CPNE3 in normal endometrium, eutopic endometrium from endometriosis, eutopic endometrium or malignant tissues from endometriosis-associated ovarian cancer. On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between BANCR, miR-612 and CPNE3, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated in vitro and in vivo. RESULTS: The expression levels of BANCR and CPNE3 were lowest in normal endometrium, significantly increased in eutopic endometrium (P < 0.05) and was significantly increased in eutopic endometrium (P < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly upregulated (P < 0.05), whereas those of miR-612 were significantly downregulated (P < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression and knockdown of BANCR in NESC and EESC upregulated and downregulated the expression of CPNE3 and promoted or prevented cell proliferation and migration, respectively; these effects were reversed by miR-612 mimics and inhibitor. These changes were all statistically significant (P < 0.05). In-vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miR-612/CPNE3 (P < 0.05). CONCLUSION: The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation, and promoted the proliferation and migration of endometrial cells via the miR-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis.

Molecular Weaving towards Flexible Covalent Organic Framework Membranes for Efficient Gas Separations.

Covalent organic frameworks (COFs) exhibit considerable potential in gas separations owing to their remarkable stability and tunable pore structures. Nevertheless, their application as gas separation membranes is hindered by limited size-sieving capabilities and poor processability. In this study, we propose a novel molecular weaving strategy that combines hydroxyl polymers and 2D TpPa-SO3H COF nanosheets, achieving high gas separation efficiency. Driven by the strong electrostatic interactions, the hydroxyl chains thread through the COF pores, effectively weaving and assembling the composites to achieve exceptional flexibility and high mechanical strength. The penetrated chains also reduce the effective pore size of COFs, and combined with the "secondary confinement effect" stemming from abundant CO2 sorption sites in the channels, the PVA@TpPa-SO3H membrane demonstrates a remarkable H2 permeance of 1267.3 GPU and an H2/CO2 selectivity of 43, surpassing the 2008 Robson upper bound limit. This facile strategy holds promise for the manufacture of large-area COF-based membranes for small-sized gas separations.

Associations of types of grains and lifestyle with all-cause mortality among Chinese adults aged 65 years or older: a prospective cohort study.

BACKGROUND: Little is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults. METHODS: Data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome. RESULTS: This study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87, 95% CI 0.80, 0.93) and 6% (HR: 0.94, 95% CI 0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86, 95% CI 0.74, 1.00) and 12% (HR: 0.88, 95% CI 0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10, 95% CI 1.03, 1.18) and 25% (HR: 1.25, 95% CI 1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13, 95% CI 1.08, 1.19) and 29% (HR: 1.29, 95% CI 1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (P for non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (P for non-linearity = 0.003). CONCLUSIONS: Specific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose-response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Nomogram to predict hemorrhagic transformation for acute ischemic stroke in Western China: a retrospective analysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is the most alarming complication of acute ischemic stroke. We aimed to identify risk factors for HT in Chinese patients and attempted to develop a nomogram to predict individual cases. METHODS: A retrospective study was used to collect the demographic and clinical characteristics of ischemic stroke patients at the Second Affiliated Hospital of Chongqing Medical University (development cohort) and Chongqing Sanbo Changan Hospital (validation cohort) from October 2013 to August 2020. Univariate analysis and multivariate analysis were used to identify the risk factors of patients in the development cohort. The nomogram was generated, and internal validation was performed. We used the area under the receiver-operating characteristic curve (AUC-ROC) to assess the discrimination and used the Hosmer-Lemeshow test to calibrate the model. To further verify the predictability and accuracy of the model, we performed an external validation of the patients in the validation cohort. RESULTS: A total of 570 patients were used to generate the nomogram. After univariate analysis and multivariate logistic regression, the remaining 7 variables (diabetes mellitus, atrial fibrillation, total cholesterol, fibrous protein, cerebral infarction area, NIHSS score and onset-to-treatment) were independent predictors of HT and used to compose the nomogram. The area under the receiver-operating characteristic curve of the model was 0.889 (95% CI, 0.841-0.938), and the calibration was good (P = 0.487 for the Hosmer-Lemeshow test). The model was validated externally with an AUC-ROC value of 0.832 (95% CI, 0.727-0.938). CONCLUSIONS: The nomogram prediction model in this study has good predictive ability, accuracy and discrimination, which can improve the diagnostic efficiency of HT in patients with acute ischemic stroke.

Mir 135a inhibits tumor cell proliferation by regulating the expression of notch pathway in hepatoblastoma.

MiRNA affects the proliferation, migration and cycle of tumor cells. However, the mechanism of regulating Notch pathway expression and inhibiting tumor cell proliferation in hepatoblastoma is not clear, we need to further explore. In this study, the dact2 gene can inhibit liver fibrosis. In this experiment, we used in vitro culture of hepatoblastoma cells and flow cytometry to detect the effect of miRNA-135a on the tumor cell cycle. The expression of miRNA-135a was detected by real-time PCR in 6 tumor samples and normal controls to observe and analyze the expression level of the important signal pathway proteins in the cells after mir-135a transfection. The cells were divided into the experimental group and the control group. The experimental group was transfected with miRNA-135a cells, while the control group was not transfected. Finally, the data are analyzed and discussed. from the third day, the activity of M17 cells in the mir-135a group began to be inhibited. By the fifth day, the inhibition rate of M17 was 50.64% (P < 0.01), and M21 was 25.02% (P < 0.01). In the experimental group, 53.38% of the cells were in the G1 phase, and mir-135a could block the tumor cells in G1 phase, affect the cell cycle process, and then affect cell proliferation.

Performance enhancement of deep-ultraviolet LEDs by using quaternary AlInGaN polarization-engineered multiple-symmetrical-stair quantum barriers without electron blocking layer.

In this paper, a structure design using quaternary AlInGaN as multiple-symmetrical-stair-shaped quantum barriers without an electron blocking layer is shown. The results show this design mitigates the droop effect to ∼0.1%, and the internal quantum efficiency reaches about 93.4%. It is believed that the better performance results from balanced electron and hole concentration and distribution of the current among the quantum wells, along with reduced non-radiative recombination. This work may be useful in the application of using quaternary AlInGaN materials as quantum barrier layers with computational simulations to design structures with electron-barrier-free layers.

The clinical profiles and outcomes of HIV-negative cryptococcal meningitis patients in type II diabetes mellitus.

BACKGROUND: The clinical profiles and outcomes of cryptococcal meningitis have been shown to vary depending on the underlying condition. The aim of this study was to investigate clinical characteristics and outcomes in patients with and without type II diabetes mellitus. METHODS: A retrospective study was performed. Clinical data of HIV-negative cryptococcal meningitis patients with type II diabetes mellitus (n = 26) and without type II diabetes mellitus (n = 52) referring to the Jiangxi Chest Hospital between January 2012 to December 2018 were analyzed. The data were analyzed using chi square, none-parametric tests, and logistic regression. P-values < 0.05 were considered significant. RESULTS: In this study, cryptococcal meningitis patients suffering from type II diabetes mellitus had a higher mortality (23.08% vs. 7.69%; P = 0.055), and required longer hospitalization (59.58 vs. 42.88 days; P = 0.132). Moreover, cerebrospinal fluid examinations revealed that cryptococcal meningitis patients with type II diabetes mellitus had higher opening pressure (271.54 vs. 234.23 mmH2O; P = 0.125).The results of multivariate regression analysis revealed that cryptococcal meningitis patients with type II diabetes were more often presented with visual disorders (28.54% vs. 11.54%; [95% CI 0.056-0.705]; p = 0.012), and had higher cerebrospinal fluid protein levels (1027.62 ± 594.16 vs. 705.72 ± 373.88 mg/l; [95% CI 1.000-1.002]; p = 0.016). Among patients with type II diabetes mellitus, nausea and vomiting was more frequent at the initial visit in those died (100% vs. 50%; p = 0.027), and 66% of died type II diabetes mellitus patients were poorly controlled blood glucose level, compared with 30% in survival type II diabetes mellitus patients. CONCLUSION: This study suggests that cryptococcal meningitis patients with type II diabetes mellitus differ significantly from cryptococcal meningitis patients without type II diabetes mellitus with respect to clinical symptoms such as visual disorders and cerebrospinal fluid examination. The presence of nausea and vomiting among type II diabetes mellitus patients could have implication in mortality.

The Change in the Neutrophil/Lymphocyte Ratio Predicts the Prognosis of Patients with Cryptococcal Meningitis.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied in many diseases. However, their roles in cryptococcal meningitis (CM) are unclear. The purpose of this article was to analyse the roles of the PLR and NLR in CM patients during treatment. METHODS: 139 newly diagnosed CM patients were enrolled. We divided patients into two groups: the successful group (n = 121) and the failure group (n = 18) based on the prognosis of patients. Then, we analyzed changes in clinical data of two groups, which were measured at the time of admission, after 2 weeks and 4 weeks in the hospital. Then the patients were divided into HIV group (n = 26) and non-HIV group (n = 113) to determine whether HIV status had an impact on the prognosis and clinical data of patients. RESULTS: Most patients were male living in rural areas; headache was the most common symptom before admission. In the subgroup analysis based on HIV status, there were significantly fewer patients with HIV (26 individuals) than without HIV (113 individuals), and 40.7% non-HIV CM patients had no underlying diseases. There was no significant difference in prognosis (p = 0.746), lymphocytes (p = 0.109) or neutrophils (p = 0.269) between patients with and without HIV. A mixed-effect model indicated that there was no difference (p = 0.171) in PLR between successful group and failure group. However, the change of NLR was statistically significant (p = 0.004 < 0.05) between successful group and failure group. CONCLUSION: An increase in the NLR during treatment may be used as an indicator of treatment failure.

Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

Sorafenib may provide survival benefits for patients with advanced hepatocellular carcinoma. However, tumor cells can display primary or secondary resistance to Sorafenib. To identify genes capable of conveying Sorafenib resistance, we performed a genome-wide CRISPR transcriptional activation library (SAM) in human Huh7 cells. We identified that a group of sgRNAs were significantly enriched in Sorafenib resistant Huh7 cells, which indicated that these sgRNAs up-regulated their target genes and induced resistance. We finally identified LRP8 as a key gene that can drive HCC cell to acquire sorafenib resistance. All three sgRNAs targeting LRP8 were identified in Sorafenib resistant Huh7 cells with high copy. We also showed that sorafenib-acquired resistant Huh7 cells have much higher LRP8 expression level than parental Huh7 cells. We proved that overexpression of LRP8 in HCC cell lines activated ß-catenin and significantly promoted its resistance to Sorafenib. We further showed that overexpression of LRP8 reduced the apoptosis level of HCC cell lines. To summary, genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

Corticosterone Signaling and a Lateral Habenula-Ventral Tegmental Area Circuit Modulate Compulsive Self-Injurious Behavior in a Rat Model.

Self-injurious behavior (SIB) is commonly observed in patients with neuropsychiatric disorders, as well as in nonclinical populations with stress-related mental-health problems. However, the exact circuitry mechanisms underlying SIB have remained poorly understood. Here, with bilateral injection of muscimol into the entopeduncular nucleus (EP), we established a rat model of SIB. Following the muscimol injection, the male rats exhibited in a dose-dependent manner stereotypic self-biting behavior that lasted for hours and often resulted in wounds of various severities. The SIB was associated with an elevated level of serum corticosterone and could be exacerbated by enhancing the corticosterone signaling and, conversely, alleviated by inhibiting the corticosterone signaling. Activity mapping using c-fos immunostaining, combined with connectivity mapping using herpes simplex virus-based anterograde tracing from the EP and pseudorabies virus-based retrograde tracing from the masseter muscle, revealed the potential involvement of many brain areas in SIB. In particular, the lateral habenula (LHb) and the ventral tegmental area (VTA), the two connected brain areas involved in stress response and reward processing, showed a significant increase in neuronal activation during SIB. Furthermore, suppressing the LHb activity or modulating the GABAergic transmission in the VTA could significantly reduce the occurrence of SIB. These results demonstrate the importance of stress hormone signaling and the LHb-VTA circuit in modulating SIB resulting from EP malfunction, and suggest potential targets for therapeutic intervention of SIB and related disorders.SIGNIFICANCE STATEMENT Self-injurious behavior (SIB) occurs in ∼4% of the general population, with substantially higher occurrence among adolescents and patients of neuropsychiatric disorders. Stress has been linked to the occurrence of SIB, yet the underlying mechanisms have remained unclear. Using a rat model of SIB induced by disruption of activity in the entopeduncular nucleus (EP), we found that the behavior is regulated by stress and linked to corticosterone signaling. Viral tracing and c-fos immunostaining revealed the involvement of various subcortical areas, especially the EP-lateral habenula (LHb)-ventral tegmental area (VTA) circuit, in SIB. Furthermore, regulating activity in the LHb or the VTA alleviates SIB. These results may have implications in the development of new strategies for treating SIB.

Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C.

Interleukin-22 (IL-22) is known to play a critical role in liver immunity. However, the role of IL-22 in HCV-associated liver fibrosis is poorly understood. In this study, patients with HCV infection disclosed significant increases in peripheral numbers of IL-22-producing cells as well as in IL-22 plasma levels. In the liver, the increased intrahepatic IL-22(+) cells were positively correlated with fibrotic staging scores and clinical progression from CHC to cirrhosis. Moreover, the majority of IL-22(+) cells were located in fibrotic areas in the liver of patients with cirrhosis and co-localized with α-smooth muscle actin (α-SMA) positive hepatic stellate cells (HSCs). In vitro, administration of IL-22 was accompanied with inhibited LX-2 cell apoptosis, promoted LX-2 cell proliferation, increased expression of α-SMA, and up-regulated collagen production by LX-2 cells. Collectively, our data provide evidence that IL-22 may contribute to the fibrogenesis of HCV-associated liver fibrosis by activating HSCs.

Phase extraction algorithm considering high-order harmonics in fringe image processing.

A phase calculation method using discrete Fourier series (DFS) is proposed to eliminate the effects of nonsinusoidal characteristics. In this method, the fundamental coefficients are extracted from continuous N samples in one cycle by DFS, with which four images with π/2 intervals are reconstructed, and then more accurate phase distribution can be further obtained. This method is applicable for improving the precision of the traditional phase-shifting algorithm. Its effectiveness and accuracy are verified by computer simulations and moiré fringe and projecting fringe experiments with about 85% of the phase error reduced compared with a four-step phase-shifting algorithm, about 70% reduction compared with a 16-step phase-shifting algorithm.

A comparative study of the therapeutic effect between long and short intramedullary nails in the treatment of intertrochanteric femur fractures in the elderly.

PURPOSE: To compare the clinical effects of long vs. short intramedullary nails in the treatment of intertrochanteric fractures in old patients more than 65 years old. METHODS: A retrospective analysis of 178 cases of intertrochanteric fractures of the femur (AO type A1 and A2) in the elderly was conducted from January 2008 to December 2013. There were 85 males (47.8%) and 93 females (52.2%) with the age of 65e89 (70.2±10.8) years. The patients were treated by closed reduction and long or short intramedullary nail (Gamma 3) fixation. The length of short nail was 180 mm and that for long nail was 320e360 mm. The general data of patients, operation time, intraoperative blood loss, length of hospital stay, preoperative hemoglobin level, blood transfusion rate, postoperative periprosthetic fractures, infections, complications, etc were carefully recorded. RESULTS: There were 76 cases (42.7%) in the long intramedullary nail group and 102 cases (57.3%) in the short nail group. All the cases were followed up for 12e48 (21.3±6.8) months, during which there were 21 deaths (11.8%), mean (13.8±6.9) months after operation. The intraoperative blood loss was (90.7±50.6) ml in short nail group, greatly less than that in long nail group (127.8±85.9) ml (p=0.004). The short nail group also had a significantly shorter operation time (43.5 min±12.3 min vs. 58.5 min±20.3 min, p=0.002) and lower rate of postoperative transfusion (42.3% vs. 56.7%, p=0.041). But the length of hospital stay showed no big differences. After operation, in each group there was 1 case of periprosthetic fracture with a total incidence of 1.1%, 1.3% in long nail group and 0.9% in short nail group. At the end of the follow-up, all patients achieved bony union. The average healing time of the long nail group was (6.5±3.1) months, and the short nail group was (6.8±3.7) months, revealing no significant differences (p=0.09). Postoperative complications showed no great differences either. CONCLUSION: Both the intramedullary long and short nail fixation has a good clinical effect in treating intertrochanteric femur fractures in the elderly. They showed no significant difference in terms of therapeutic effect, hospital stay and postoperative complications. The incidence of periprosthetic fractures treated by either length of nails was low. But short intramedullary nailing can obviously decrease the intraoperative blood loss, operation time and postoperative blood transfusion.

The paralogous SPX3 and SPX5 genes redundantly modulate Pi homeostasis in rice.

The importance of SPX-domain-containing proteins to phosphate (Pi) homeostasis and signalling transduction has been established in plants. In this study, phylogenetic analysis revealed that OsSPX3 and OsSPX5 (SPX3/5) are paralogous SPX genes ( SYG1/Pho81/XPR1) in cereal crops. SPX3/5 are specifically responsive to Pi starvation at both the transcriptional and post-transcriptional levels. Similar tissue expression patterns of the two genes and proteins were identified by in situ hybridization and the transgenic plants harbouring SPX3pro-SPX3-GUS or SPX5pro-SPX5-GUS fusions, respectively. Both SPX3/5 are localized in the nucleus and cytoplasm in rice protoplasts and plants. SPX3/5 negatively regulate root-to-shoot Pi translocation with redundant function. The data showed that the Pi-starvation-accumulated SPX3/5 proteins are players in restoring phosphate balance following phosphate starvation. In vitro and in vivo protein-protein interaction analyses indicated that these two proteins can form homodimers and heterodimers, also implying their functional redundancy. Genetic interaction analysis indicated that SPX3/5 are functional repressors of OsPHR2 (PHR2), the rice orthologue of the central regulator AtPHR1 for Pi homeostasis and Pi signalling. These results suggest that the evolution of the additional redundant paralogous SPX genes is beneficial to plants recovering Pi homeostasis after Pi starvation by PHR2 pathway.

Clinical implication of TMPRSS4 expression in human gallbladder cancer.

Altered expression of transmembrane protease/serine 4 (TMPRSS4) is observed in various types of human cancers. However, the clinical significance of TMPRSS4 expression in gallbladder cancer (GBC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of TMPRSS4 in GBC. The levels of TMPRSS4 mRNA and protein in GBC tissues and adjacent noncancerous tissues were evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry. To investigate the correlations between TMPRSS4 and the clinicopathological features of GBC, the expression of TMPRSS4 in 97 patients with GBC were detected by immunohistochemistry. The correlation of TMPRSS4 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of TMPRSS4 mRNA and protein in GBC tissues were both significantly higher than those in adjacent noncancerous tissues. Immunohistochemical staining revealed that high TMPRSS4 expression was closely correlated with tumor size (P=0.032), histological grade (P=0.002), pathologic T stage (P=0.005), clinical stage (P=0.013), and lymph node metastasis (P=0.003). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of TMPRSS4 resulted in a significantly poor prognosis of GBC patients. Multivariate analysis showed that the status of TMPRSS4 expression was an independent prognostic factor for GBC patients. Our results showed that TMPRSS4 plays a key role in GBC and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in GBC.

Feasibility of novel intraoperative navigation for anatomical liver resection using real-time virtual sonography combined with indocyanine green fluorescent imaging technology.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.

Enriched environment treatment promotes neurofunctional recovery by regulating the ALK5/Smad2/3/Gadd45ß signaling pathway in rats with cerebral ischemia /reperfusion injury.

It has been demonstrated that an enriched environment (EE) treatment can alter neuroplasticity in neurodegenerative diseases. However, the role of EE treatment in ischemic stroke remains unclear. Previous findings have revealed that EE treatment can promote cerebral activin-receptor-like-kinase-5 (ALK5) expression after cerebral ischemia/reperfusion (I/R) injury. ALK5 has been identified as a potential mediator of neuroplasticity through its modulation of Smad2/3 and Gadd45ß. Therefore, the aim of this study was to investigate whether EE treatment could promote neurofunctional recovery by regulating the ALK5/Smad2/3/Gadd45ß pathway. The study utilized the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). The ALK5/Smad2/3/Gadd45ß signaling pathway changes were evaluated using western blotting (WB). Brain injury was assessed by infarct volume and neurobehavioral scores. The effect of EE treatment on neurogenesis was evaluated using Doublecortin (DCX) and Nestin, axonal plasticity with biotinylated dextran amine (BDA) nerve tracing, and dendritic plasticity was assessed using Golgi-Cox staining. EE treatment has been demonstrated to modulate the Smad2/3/Gadd45ß pathway by regulating the expression of ALK5. The protective effects of EE treatment on brain infarct volume, neurological function, newborn neurons, dendritic and axonal plasticity following cerebral I/R injury were counteracted by ALK5 silencing. EE treatment can enhance neurofunctional recovery after cerebral I/R injury, which is achieved by regulating the ALK5/Smad2/3/Gadd45ß signaling pathway to promote neuroplasticity.

Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing.

BACKGROUND: The immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage-related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established. OBJECTIVE: This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions. METHODS AND RESULTS: Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage-specific knockout of Trem2 (T2-cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)-4 binds directly to Trem2, inactivating MAPK/AP-1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co-culture of fibroblasts and macrophages showed that macrophages from T2-cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing. CONCLUSIONS: These analyses offer novel insight into the role of IL-4/Trem2 signalling as a mediator of myeloid cell-fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.