Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.

Background: Deficiencies in DNA damage repair responses promote chemotherapy sensitivity of tumor cells. The Nibrin homolog encoding gene Nijmegen Breakage Syndrome 1 (NBS1) is a crucial component of the MRE11-RAD50-NBN complex (MRN complex) and is involved in the response to DNA double-strand breaks (DSBs) repair that has emerged as an attractive strategy to overcome tumor drug resistance, but the functional relationship between NBS1 regulated DNA damage repair and cell cycle checkpoints has not been fully elucidated. Methods: In this study, lentivirus-mediated RNAi was used to construct NBS1-downregulated cells. Flow cytometry, qPCR, and immunohistochemistry were used to explore the regulatory relationship between NBS1 and CyclinB in vivo and in vitro. Results: Our findings suggest that NBS1 deficiency leads to defective homologous recombination repair. Inhibition of NBS1 expression activates CHK1 and CyclinB signaling pathways leading to cell cycle arrest and sensitizes ovarian cancer cells to Olaparib treatment in vitro and in vivo. NBS1-deficient ovarian cancer cells tend to maintain sensitivity to chemotherapeutic drugs through activation of cell cycle checkpoints. Conclusions: NBS1 may be a potential therapeutic target for epithelial ovarian cancer as it plays a role in the regulation of the DNA damage response and cell cycle checkpoints. Suppression of NBS1 upregulates CyclinB to induce Olaparib sensitivity in ovarian cancer.

Semiquantitative magnetic resonance imaging parameters for differentiating parotid pleomorphic adenoma from Warthin tumor.

Background: Accurately distinguishing between pleomorphic adenoma (PA) and Warthin tumor (WT) is beneficial for their respective management. Preoperative magnetic resonance imaging (MRI) can provide valuable information due to its excellent soft tissue contrast. This study explored the value of semiquantitative contrast-enhanced MRI parameters in the differential diagnosis of PA and WT. Methods: Data from 106 patients, 62 with PA and 44 with WT (confirmed by histopathology) were retrospectively and consecutively analyzed. The tumor-to-spinal cord contrast ratios (TSc-CR) based on the mean, maximum, and minimum signal intensity (T1-mean TSc-CR, T1-max TSc-CR, and T1-min TSc-CR, respectively) in the early and delayed phases were calculated on contrast-enhanced T1-weighted images as semiquantitative parameters, and then compared between PA and WT. Receiver operating characteristic (ROC) curve analysis and areas under the curve (AUCs) were used to determine the performance of these parameters in the differential diagnosis of PA from WT. Results: Except T1-min TSc-CR in the early phase, all semiquantitative MRI parameters differed significantly between PA and WT (all P<0.05). T1-max TSc-CR showed higher sensitivity {70.45% [95% confidence interval (CI): 0.548-0.832]} and specificity [70.97% (95% CI: 0.581-0.818)] and had a higher AUC [0.707 (95% CI: 0.610-0.791)] in the early phase when using a cutoff value of 1.89. T1-max TSc-CR showed higher sensitivity [88.64% (95% CI: 0.754-0.962)], specificity [72.58% (95% CI: 0.598-0.831)], and AUC [0.854 (95% CI: 0.772-0.915)] in the delayed phase when using a cutoff value of 2.33. The sensitivity, specificity, and AUC were improved to 90.91% (95% CI: 0.783-0.975), 93.55% (95% CI: 0.843-0.982), and 0.960 (95% CI: 0.903-0.988), respectively, after combination of all semiquantitative parameters in the early and delayed phases. The two radiologists had excellent interobserver agreement on TSc-CRs [all interclass correlation coefficient (ICC) >0.75]. Conclusions: Semiquantitative parameters using TSc-CR are valuable in distinguishing PA from WT, and a combination of these parameters can improve the differential diagnostic efficiency.

Bone marrow immune cells respond to fluctuating nutritional stress to constrain weight regain.

Weight regain after weight loss is a major challenge in the treatment of obesity. Immune cells adapt to fluctuating nutritional stress, but their roles in regulating weight regain remain unclear. Here, we identify a stem cell-like CD7+ monocyte subpopulation accumulating in the bone marrow (BM) of mice and humans that experienced dieting-induced weight loss. Adoptive transfer of CD7+ monocytes suppresses weight regain, whereas inducible depletion of CD7+ monocytes accelerates it. These cells, accumulating metabolic memories via epigenetic adaptations, preferentially migrate to the subcutaneous white adipose tissue (WAT), where they secrete fibrinogen-like protein 2 (FGL2) to activate the protein kinase A (PKA) signaling pathway and facilitate beige fat thermogenesis. Nevertheless, CD7+ monocytes gradually enter a quiescent state after weight loss, accompanied by increased susceptibility to weight regain. Notably, administration of FMS-like tyrosine kinase 3 ligand (FLT3L) remarkably rejuvenates CD7+ monocytes, thus ameliorating rapid weight regain. Together, our findings identify a unique bone marrow-derived metabolic-memory immune cell population that could be targeted to combat obesity.

Protective Effect of a Novel RIPK1 Inhibitor, Compound 4-155, in Systemic Inflammatory Response Syndrome and Sepsis.

Excessive inflammatory response is a critical pathogenic factor for the tissue damage and organ failure caused by systemic inflammatory response syndrome (SIRS) and sepsis. In recent years, drugs targeting RIPK1 have proved to be an effective anti-inflammatory strategy. In this study, we identified a novel anti-inflammatory lead compound 4-155 that selectively targets RIPK1. Compound 4-155 significantly inhibited necroptosis of cells, and its activity is about 10 times higher than the widely studied Nec-1 s. The anti-necroptosis effect of 4-155 was mainly dependent on the inhibition of phosphorylation of RIPK1, RIPK3, and MLKL. In addition, we demonstrated that 4-155 specifically binds RIPK1 by drug affinity responsive target stability (DARTS), immunoprecipitation, kinase assay, and immunofluorescence microscopy. More importantly, compound 4-155 could inhibit excessive inflammation in vivo by blocking RIPK1-mediated necroptosis and not influence the activation of MAPK and NF-κB, which is more potential for the subsequent drug development. Compound 4-155 effectively protected mice from TNF-induced SIRS and sepsis. Using different doses, we found that 6 mg/kg oral administration of compound 4-155 could increase the survival rate of SIRS mice from 0 to 90%, and the anti-inflammatory effect of 4-155 in vivo was significantly stronger than Nec-1 s at the same dose. Consistently, 4-155 significantly reduced serum levels of pro-inflammatory cytokines (TNF-α and IL-6) and protected the liver and kidney from excessive inflammatory damages. Taken together, our results suggested that compound 4-155 could inhibit excessive inflammation in vivo by blocking RIPK1-mediated necroptosis, providing a new lead compound for the treatment of SIRS and sepsis.

Naringenin and apigenin ameliorates corticosterone-induced depressive behaviors.

Background: Depression is a common kind of mental illness, and it becomes the main health burden in the world. Purpose: The aim of this study was to investigate the antidepressant effects of naringin and apigenin isolated from Chrysanthemum morifolium Ramatis. Methods: Firstly, 20 mg/kg corticosterone (CORT) was injected into mice to establish an in vivo model of depression. After treated with different dosages of naringenin and apigenin for 3 weeks, the mice underwent a series of behavioral experiments. Following this, all mice were sacrificed and biochemical analyses were performed. Subsequently, CORT (500 µM) induced PC12 cells was used as an in vitro model of depression, and lipopolysaccharide (LPS) (1 µg ml-1) induced N9 microglia cells was used as an in vitro model of neuroinflammation in N9 microglia cells, to investigate the neuroprotective mechanisms of naringenin and apigenin. Results: Results showed that the naringenin and apigenin treatment ameliorated CORT-induced sucrose preference decrease and immobility time increase, elevated the 5-hydroxytryptamine(5-HT), dopamine (DA) and norepinephrine (NE) levels, and enhanced the cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) protein expressions in the hippocampus. The results showed that the naringenin and apigenin treatment improved the PC-12 cell viability through reducing apoptosis rate induced by CORT. Furthermore, naringenin and apigenin were able to inhibit the activation of N9 cells after LPS induction, and shift microglia from proinflammatory M1 microglia toward anti-inflammatory M2 microglia, as evidenced by the decreased ratio of M1 type microglia marker CD86 and M2 type microglia marker CD86. Conclusion: These results suggested that naringenin and apigenin may improve depressive behaviors through promoting BDNF and inhibiting neuroinflammation and neuronal apoptosis.

Corrigendum: Elucidation of the mechanism underlying impaired sensorimotor gating in patients with primary blepharospasm using prepulse inhibition.

[This corrects the article DOI: 10.3389/fneur.2023.1105483.].

ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma.

BACKGROUND: Sustained activation of hepatocyte growth factor (HGF)/c-MET signaling is a major driver of hepatocellular carcinoma (HCC) progression, but underlying mechanism is unclear. ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 2 (ASAP2) can reportedly activate GTPases and promote receptor tyrosine kinase signaling. However, the exact role of ASAP2 in HCC, especially for c-MET activation, also remains elusive. METHODS: ASAP2 expression levels in HCC tissues and cells were quantified using qRT-PCR, western blot (WB) analysis, and immunohistochemistry staining. Cell counting kit-8 (CCK-8) and colony formation assays were performed to evaluate cell proliferation rates. Flow cytometry assays were conducted to assess apoptosis rates. Wound healing and Transwell assays were performed to determine cell migration and invasion capacities. Epithelial-mesenchymal transition (EMT)-related marker expression levels were also examined. Subcutaneous implantation and tail vein injection models were applied for in vivo growth and metastasis evaluations, respectively. Bioinformatics analyses of The Cancer Genome Atlas and STRING datasets were performed to explore ASAP2 downstream signaling. Co-immunoprecipitation and Cycloheximide chasing experiments were performed to assess protein-protein interactions and protein half-life, respectively. RESULTS: ASAP2 had higher expression levels in HCC tissues than in normal liver, and also predicted poor prognosis. Knocking down ASAP2 significantly impaired cell proliferation, migration, and invasion capacities, but promoted apoptosis in HCC cells in vitro. However, overexpression of ASAP2 achieved the opposite effects. In vivo experiments confirmed that ASAP2 could promote HCC cell growth and facilitate lung metastasis. Interestingly, ASAP2 was essential for triggering EMT. Gene Set Enrichment Analysis demonstrated that c-MET signaling was greatly enriched in ASAP2-high HCC cases. Additionally, c-MET signaling activity was significantly decreased following ASAP knockdown, evidenced by reduced c-MET, p-AKT, and p-ERK1/2 protein levels. Importantly, ASAP2 knockdown effectively attenuated HGF/c-MET signaling-induced malignant phenotypes. c-MET and ASAP2 expression levels were positively correlated in our cohort. Mechanistically, ASAP2 can directly bind to CIN85, thereby disrupting its interaction with c-MET, and can thus antagonize CIN85-induced c-MET internalization and lysosome-mediated degradation. Notably, knocking down CIN85 can rescue the observed inhibitory effects caused by ASAP2 knockdown. CONCLUSIONS: This study highlights the importance of ASAP2 in sustaining c-MET signaling, which can facilitate HCC progression.

Elucidation of the mechanism underlying impaired sensorimotor gating in patients with primary blepharospasm using prepulse inhibition.

Objective: We aimed to analyze prepulse inhibition (PPI) impairment of the blink reflex in patients with primary blepharospasm (BSP). Methods: We recruited 30 BSP patients and 20 gender- and age-matched healthy controls (HCs). Weak electrical stimulation was applied to the right index finger at interstimulus intervals (ISIs) of 120, 200, and 300 ms before the supraorbital nerve stimulation to investigate PPI size [PPI size = (1 - R2 area at prepulse trials/R2 area at baseline trials) × 100%]. Results: The prepulse stimulus significantly inhibited the R 2 component at the three ISIs in both groups, but less inhibition was shown in the BSP group (p < 0.05). In HCs, the prepulse stimulus induced prolonged R 2 and R 2c latencies at the three ISIs and increased the R 1 amplitude at ISIs of 120 ms; these changes were absent in BSP patients. In the BSP group, patients with sensory tricks showed better PPI than patients without sensory tricks. Disease duration and motor symptom severity showed no significant correlation with PPI size. Conclusion: In BSP patients, PPI was impaired while R 1 facilitation was absent. PPI size did not correlate with the motor symptom severity and disease duration. Patients with sensory tricks showed better PPI than those without sensory tricks.

Evaluation of natural ageing responses on Burmese amber durability by FTIR spectroscopy with PLSR and ANN models.

Amber ageing is an inevitable process, which is very important in precious organic gemstone relics protection. In order to explore the mechanism of amber ageing and estimate the durability of Burmese amber, this research investigates the changing spectral features of Burmese ageing amber via Fourier Transform Infrared Spectroscopy (FTIR) and solid 13C Nuclear Magnetic Resonance spectroscopy (NMR) and develops the regression models for its micro-hardness by micro-FTIR spectra. The Partial Least Squares Regression (PLSR) and Artificial Neural Networks (ANN) methods as well as Competitive Adaptive Reweighted Sampling (CARS) algorithm for wavelength variables selection have been applied to predict and assess the Vickers hardness of amber samples with different ageing degrees. As a result, the FTIR and the solid 13C NMR spectra reveal that the contents of CO groups (of esters) increase substantially, and which of the other oxygenic groups (CO (of acids), COC, COCC) increase modestly in amber ageing. When comparing with the results of four different models (PLSR, ANN, CARS-PLSR and CARS-ANN), the CARS-PLSR model obtained the optimal results as follows: the squared correlation coefficient of calibration(R2cal) is 0.9230 and the root mean square error of calibration (RMSEC) is 1.2977 HV; the squared correlation coefficient of prediction (R2pre) is 0.7762 and the root mean square error of prediction (RMSEP) is 2.2208 HV. The overall results sufficiently demonstrate that FTIR spectroscopy technique coupled with appropriate chemometrics methods are very promising tools to estimate and predict the hardness property of Burmese ageing amber.

Efficacy and safety of endoscopic diaphragm incision in children with congenital duodenal diaphragm / 中华儿科杂志

Objective: To explore the efficacy and safety of endoscopic diaphragm incision in pediatric congenital duodenal diaphragm. Methods: Eight children with duodenal diaphragm treated by endoscopic diaphragm incision in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from October 2019 to May 2022 were enrolled in this study. Their clinical data including general conditions, clinical manifestations, laboratory and imaging examinations, endoscopic procedures and outcomes were retrospectively analyzed. Results: Among the 8 children, 4 were males and 4 females. The diagnosis was confirmed at the age of 6-20 months; the age of onset was 0-12 months and the course of disease was 6-18 months. The main clinical manifestations were recurrent non-biliary vomiting, abdominal distension and malnutrition. One case complicated with refractory hyponatremia was first diagnosed with atypical congenital adrenal hyperplasia in the endocrinology department. After treatment with hydrocortisone, the blood sodium returned to normal, but vomiting was recurrent. One patient underwent laparoscopic rhomboid duodenal anastomosis in another hospital but had recurred vomiting after the operation, who was diagnosed with double duodenal diaphragm under endoscope. No other malformations were found in all the 8 cases. The duodenal diaphragm was located in the descending part of the duodenum, and the duodenal papilla was located below the diaphragm in all the 8 cases. Three cases had the diaphragm dilated by balloon to explore the diaphragm opening range before diaphragm incision; the other 5 had diaphragm incision performed after probing the diaphragm opening with guide wire. All the 8 cases were successfully treated by endoscopic incision of duodenal diaphragm, with the operation time of 12-30 minutes. There were no complications such as intestinal perforation, active bleeding or duodenal papilla injury. At one month of follow-up, their weight increased by 0.4-1.5 kg, with an increase of 5%-20%. Within the postoperative follow-up period of 2-20 months, all the 8 children had duodenal obstruction relieved, without vomiting or abdominal distension, and all resumed normal feeding. Gastroscopy reviewed at 2-3 months after the operation in 3 cases found no deformation of the duodenal bulbar cavity, and the mucosa of the incision was smooth, with a duodenal diameter of 6-7 mm. Conclusion: Endoscopic diaphragm incision is safe, effective and less invasive in pediatric congenital duodenal diaphragm, with favorable clinical applicability.

Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson's disease: An fNIRS study.

INTRODUCTION: The use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). METHODS: We recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. RESULTS: Compared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. CONCLUSION: These findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.

H-NS Represses Biofilm Formation and c-di-GMP Synthesis in Vibrio parahaemolyticus.

Objective: This study aimed to investigate the regulation of histone-like nucleoid structuring protein (H-NS) on biofilm formation and cyclic diguanylate (c-di-GMP) synthesis in Vibrio parahaemolyticus RIMD2210633. Methods: Regulatory mechanisms were analyzed by the combined utilization of crystal violet staining, quantification of c-di-GMP, quantitative real-time polymerase chain reaction, LacZ fusion, and electrophoretic-mobility shift assay. Results: The deletion of hns enhanced the biofilm formation and intracellular c-di-GMP levels in V. parahaemolyticus RIMD2210633. H-NS can bind the upstream promoter-proximal DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979 to repress their transcription. These genes encode a group of proteins with GGDEF and/or EAL domains associated with c-di-GMP metabolism. Conclusion: One of the mechanisms by which H-NS represses the biofilm formation by V. parahaemolyticus RIMD2210633 may be via repression of the production of intracellular c-di-GMP.

Neutrophil extracellular traps in fungal infections: A seesaw battle in hosts.

Fungal infections are a growing health care challenge. Neutrophils play a key role in defense against fungal infections. There are many effective ways for neutrophils to eliminate fungal invaders, such as phagocytosis, oxidative bursts, and the formation of extracellular traps. This process has received considerable attention and has made rapid progress since neutrophil extracellular traps (NETs) formation was described. Here, we describe the formation, induction, and function of NETs, as well as fungal strategies against NETs hunting. We highlight the effects of NETs on common fungal pathogens and how these pathogens survive.

Identification of a novel Calpain-2-SRC feed-back loop as necessity for ß-Catenin accumulation and signaling activation in hepatocellular carcinoma.

Rapid progression is the major cause of the poor prognosis of hepatocellular carcinoma (HCC); however, the underlying mechanism remained unclear. Here, we found Calpain-2 (CAPN2), a well-established protease that accelerates tumor progression in several malignancies, is overexpressed in HCC and acts as an independent predictor for poor outcomes. Furthermore, CAPN2 promoted the proliferation and invasion of HCC, and showed a positive correlation with the levels of invasion-related markers. Mechanistically, a novel CAPN2-SRC positive regulatory loop was identified upstream of ß-catenin to prevent its ubiquitination and degradation, and subsequently promoted HCC progression: CAPN2 could proteolyze PTP1B to form a truncation of approximately 42 kDa with increased phosphatase activity, resulting in reduced SRC Y530 phosphorylation and increased SRC kinase activity; meanwhile, CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. Interestingly, the CAPN2-SRC loop could not only restrain most of cytoplasmic ß-catenin degradation by inhibiting GSK3ß pathway, but also prevented TRIM33-induced nuclear ß-catenin degradation even in ß-catenin-mutant cells. Present study identified a CAPN2-SRC positive loop responsible for intracellular ß-catenin accumulation and signaling activation, and targeting CAPN2 protease activity might be a promising approach for preventing HCC progression.

[Modification of quicklime on acid soil under forest and their effect on the growth of Panax notoginseng]. / ç”ŸçŸ³ç°å¯¹æž—ä¸‹é ¸åŒ–åœŸå£¤çš„è°ƒæŽ§ä½œç”¨åŠä¸‰ä¸ƒç”Ÿé•¿çš„å½±å“.

Soil acidification is an important factor leading to poor growth and root rot disease of Panax notoginseng in the understorey of forests. In this study, different amounts of quicklime (0, 500, 1000, 1500 and 2000 kg·hm-2) were amended into acid soil under forest. We evaluated the effect of quikelime addition on soil chemical properties, phenols, rhizosphere microorganisms and growth of P. notoginseng. The results showed that an appro-priate amount of quicklime addition (500-1000 kg·hm-2) could significantly increase soil pH, decrease the content of phenols (p-hydroxybenzoic acid, vanillin, syringic acid, ferulic acid and vanillic acid), promote P. notoginseng growth, and reduce the incidence of root rot disease. An appropriate amount of quicklime (500-1000 kg·hm-2) could significantly reduce the fungi:bacteria ratio, increase bacteria diversity, and increase the relative abundance of Ascomycota and Proteobacteria as well as Massilia and Sphingomonas. However, excessive quicklime addition (1500-2000 kg·hm-2) could reduce the content of available nitrogen and organic matter, and inhibit P. notoginseng growth. Therefore, 500-1000 kg·hm-2 of quicklime amendment could improve the chemical properties and microbial community of acid soil under forest, thereby promoting P. notoginseng growth, and reducing the incidence of root rot disease.

Antifungal and Immunomodulatory Ingredients from Traditional Chinese Medicine.

Fungal infections have become a growing public health challenge due to the clinical transmission of pathogenic fungi. The currently available antifungal drugs leave very limited choices for clinical physicians to deal with such situation, not to mention the long-standing problems of emerging drug resistance, side effects and heavy economic burdens imposed to patients. Therefore, new antifungal drugs are urgently needed. Screening drugs from natural products and using synthetic biology strategies are very promising for antifungal drug development. Chinese medicine is a vast library of natural products of biologically active molecules. According to traditional Chinese medicine (TCM) theory, preparations used to treat fungal diseases usually have antifungal and immunomodulatory functions. This suggests that if antifungal drugs are used in combination with immunomodulatory drugs, better results may be achieved. Studies have shown that the active components of TCM have strong antifungal or immunomodulatory effects and have broad application prospects. In this paper, the latest research progress of antifungal and immunomodulatory components of TCM is reviewed and discussed, hoping to provide inspiration for the design of novel antifungal compounds and to open up new horizons for antifungal treatment strategies.

Study of end-to-end magnetic anastomosis technique of infrahepatic inferior vena cava in rats / 器官移植

Objective To develop a magnetic anastomosis device for infrahepatic inferior vena cava and verify its feasibility and safety in rat models. Methods According to the anatomical characteristics of rat inferior vena cava, a magnetic device suitable for end-to-end anastomosis of infrahepatic inferior vena cava was designed and manufactured. The device consisted of the inner and outer rings. The inner ring was a coated neodymium-iron-boron magnetic ring, and the outer ring was made of polyetheretherketone by 3D printing. Ten fine holes are evenly distributed on the outer ring, of which 5 fine holes were used to load the fine needles, and the other 5 fine holes were mutually connected with the fine needles of the contralateral anastomosis ring during anastomosis. The outer ring was uniformly loaded with fine needles and then bonded with the inner ring to form a magnetic anastomosis complex. Bilateral ends of vessels passed through the anastomosis ring and were fixed to the fine needles, and then end-to-end vascular anastomosis was performed by mutual attraction of two magnetic anastomosis rings. Twenty SD rats were selected and received end-to-end anastomosis of infrahepatic inferior vena cava with magnetic anastomosis device. The time of vascular occlusion, postoperative survival, postoperative anastomotic patency, gross observation and histological examination of anastomotic stoma were analyzed. Results All rats successfully completed end-to-end magnetic anastomosis of the infrahepatic inferior vena cava, and the time of vascular occlusion was 4~6 min. One rat died at 10 d after operation, and the other rats survived within postoperative 2 months. The patency rates of anastomotic stoma in surviving rats at postoperative 1 d, 3 d, 1 month and 2 months were 100%, 100%, 95% and 95%, respectively. At 2 months after operation, no obvious displacement and angulation of the anastomosis device were seen. No signs of corrosion and cracking of the anastomosis rings were observed. No evident hyperplasia and edema of surrounding tissues were noted. Bilateral ends of vessels were completely healed, and no obvious stenosis or thrombosis was found at the anastomotic stoma. Histological examination showed high continuity of bilateral vascular walls of anastomotic stoma, the inner surface of anastomotic stoma was covered by endothelial cells, and no thrombus or fibrous tissue was attached. Conclusions It is safe and feasible to utilize the self-designed magnetic anastomosis device to perform end-to-end magnetic anastomosis of infrahepatic inferior vena cava in rat models.

Serum HER2 levels predict treatment efficacy and prognosis in patients with HER2-positive breast cancer undergoing neoadjuvant treatment.

BACKGROUND: Controversy remains regarding the predictive and prognostic value of serum human epidermal growth factor receptor 2 (HER2) in breast cancer. The purpose of this retrospective study was to determine the clinical utility and efficacy of serum HER2 (sHER2) in predicting treatment response and prognosis in patients with HER2-positive breast cancer undergoing neoadjuvant chemotherapy and trastuzumab treatment. METHODS: A total of 309 HER2-positive breast cancer patients diagnosed at Fudan University Shanghai Cancer Center from July 2015 to January 2019 were analyzed. Baseline sHER2 levels were obtained for all patients and sHER2 levels were collected after 2 cycles of treatment in 208 patients. A sHER2 level ≥15 ng/mL was regarded as "high expression" and sHER2 <15 ng/mL was regarded as "low expression". Outcome measures of treatment efficacy and prognosis were pathological complete response (pCR) and invasive disease-free survival (iDFS), respectively. RESULTS: In patients with high baseline sHER2, more were ER-negative (P=0.029), had larger tumor size (P=0.006), more advanced clinical stage (P=0.002), higher Miller-Payne grade (P=0.024) and higher likelihood of iDFS events (P=0.015). Patients with high sHER2 levels after 2 cycles of treatment had lower pCR rates (P=0.038), higher Miller-Payne grade (P=0.013) and higher likelihood of iDFS events (P=0.003). Kaplan-Meier analysis showed significant differences in iDFS between patients with high and low sHER2 levels at baseline (P=0.019) and after 2 cycles of treatment (P=0.000). Further analyses according to cancer subtypes found baseline sHER2 to be significantly correlated with the iDFS of Luminal B patients (p=0.002), while sHER2 levels after 2 cycles of treatment was significantly correlated with the iDFS of HER2-enriched patients (P=0.000). Univariate analysis showed significant association between iDFS and tumor size (P=0.026), lymph node status (P=0.008), clinical stage (P=0.031), baseline sHER2 (P=0.024), overall tumor response (P=0.011), pCR (P=0.043) and Miller-Payne grade (P=0.001). Multivariate analysis found Miller-Payne grade (P=0.037) to be significantly associated with iDFS. CONCLUSIONS: Our results demonstrate the clinical value of sHER2 in a population of Chinese breast cancer patients, suggesting that sHER2 levels after 2 cycles of neoadjuvant therapy may be more predictive of treatment outcomes and that the prognostic value of sHER2 may be time point and subtype dependent.

Customizable design strategies for high-performance bioanodes in bioelectrochemical systems.

Bioelectrochemical systems (BESs) can fulfill the demand for renewable energy and wastewater treatment but still face significant challenges to improve their overall performance. Core efforts have been made to enhance the bioelectrode performance, yet, previous approaches are fragmented and have limited applicability, unable to flexibly adjust physicochemical and structural properties of electrodes for specific requirements in various applications. Here, we propose a facile electrode design strategy that integrates three-dimensional printing technology and functionalized modular electrode materials. A customized graphene-based electrode with hierarchical pores and functionalized components (i.e., ferric ions and magnetite nanoparticles) was fabricated. Owing to efficient mass and electron transfer, a high volumetric current density of 10,608 ± 1,036 A/m3 was achieved, the highest volumetric current density with pure Geobacter sulfurreducens to date. This strategy can be readily applied to existing BESs (e.g., microbial fuel cells and microbial electrosynthesis) and provide a feasibility for practical application.