CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis.

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.

Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer during Neoadjuvant Chemoradiation.

BACKGROUND: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines. RESULTS: Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03-2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025). CONCLUSIONS: Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%.

Increased resected lymph node stations improved survival of esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT. METHODS: The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used. RESULTS: In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups. CONCLUSION: This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.

Impact of deep muscle invasion on nodal status and survival in patients with pT2 esophageal squamous cancer.

BACKGROUND: Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. METHODS: We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan‒Meier analysis and a Cox proportional hazard regression model. RESULTS: A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). CONCLUSIONS: We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.

Mapping of lymph node metastasis from esophageal squamous cell carcinoma after neoadjuvant treatment: a prospective analysis from a high-volume institution in China.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

Structural Design of Intelligent Reversible Two-Way Structural Color Films.

Structural color always shows a reversible switch between reflection and transmission states when viewed from different angles, attracting increasing attention in display applications. However, this switching between reflection and transmission states of structural color suffers from the inherent lack of autonomous regulation, which is unmanageable in the case of different application scenarios. Here, we design an intelligent two-way structural color film which can reversibly change its color when applied with an extra stimulation such as voltage, heat signal, or light. A special structural feature contains a traditional photonic crystal film of polystyrene (PS) microspheres assembled by smart windows. Remarkably, our structural color film shows a prominent polarization sensitivity, and the angle dependence of the structural color broadens the gamut of display color demonstrated by both finite element theoretical analysis and experimental observation. Prospectively, this hierarchically designed film provides a promising pathway toward next-generation multicolor displays and smart windows.

Longer Time Interval from Neoadjuvant Chemoradiation to Surgery is Associated with Poor Survival for Patients Without Clinical Complete Response in Oesophageal Cancer.

BACKGROUND: The optimal interval between neoadjuvant therapy and oesophagectomy for oesophageal cancer remains controversial. METHODS: Patients with locally advanced oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy followed by oesophagectomy between June 2017 and December 2020 were prospectively enrolled and retrospectively analysed. Patients were divided into two groups: timely (group A; < 10 weeks) and delayed (group B; ≥ 10 weeks) surgery groups. Survival was the primary outcome, and tumour response and post-operative complications were the secondary outcomes. RESULTS: Overall, 224 patients were recruited; 116 patients (51.8%) underwent timely surgery within 10 weeks (group A), and 108 patients (49.2%) underwent delayed surgery over 10 weeks (group B) after chemoradiotherapy. In patients with clinical complete response (cCR), two groups had no significant difference of survival benefit (P = 0.618). However, in patients without cCR, delayed surgery was associated with poor survival (P = 0.035) and cancer progression (P = 0.036). A total of 40 patients (34.5%) in group A and 54 patients (50.0%) in group B achieved pCR (P = 0.019). pCR rates were significantly different across the four groups and increased over time (P = 0.006). CONCLUSIONS: Patients with a prolonged time interval from neoadjuvant chemoradiation to surgery had higher pCR rates. For patients with cCR to neoadjuvant chemoradiation, the time interval to surgery can be safely prolonged for at least 10 weeks. However, for patients with non-cCR to neoadjuvant chemoradiation, delayed surgery is associated with poor survival, and surgery should be performed within 10 weeks of neoadjuvant chemoradiation.

Biomimetic synthesis of hydroxytyrosol from conversion of tyrosol by mimicking tyrosine hydroxylase.

Hydroxytyrosol, one of the most powerful natural antioxidants, exhibits certificated benefits for human health. In this study, a biomimetic approach to synthesize hydroxytyrosol from the hydroxylation of tyrosol was established. EDTA-Fe2+ coordination complex served as an active center to simulate tyrosine hydroxylase. H2O2 and ascorbic acid were used as oxygen donor and hydrogen donor, respectively. Hydroxy radical and singlet oxygen contributed to active species. The biomimetic system displayed analogous component, structure, and activity with TyrH. Hydroxytyrosol titer of 21.59 mM, and productivity of 9985.92 mg·L-1·h-1 was achieved with 100 mM tyrosol as substrate. The proposed approach provided efficient and convenient route to quickly produce high amount of hydroxytyrosol.

Fads2b Plays a Dominant Role in ∆6/∆5 Desaturation Activities Compared with Fads2a in Common Carp (Cyprinus carpio).

Highly unsaturated fatty acids (HUFAs) are essential for mammalian health, development and growth. However, most mammals, including humans, are incapable of synthesizing n-6 and n-3 HUFAs. Fish can convert C18 unsaturated fatty acids into n-6 and n-3 HUFAs via fatty acid desaturase (Fads), in which Fads2 is a key enzyme in HUFA biosynthesis. The allo-tetraploid common carp theoretically encode two duplicated fads2 genes. The expression patterns and desaturase functions of these two homologous genes are still unknown. In this study, the full length of the fads2a and fads2b were identified in common carp (Cyprinus carpio). Expression analyses indicate that both genes were mainly expressed in the liver and the expression of fads2b is higher than fads2a at different developmental stages in carp embryos. Heterogenous expression and 3D docking analyses suggested that Fads2b demonstrated stronger ∆6 and ∆5 desaturase activities than Fads2a. The core promotor regions of fads2a and fads2b were characterized and found to have different potential transcriptional binding sites. These results revealed the same desaturase functions, but different activities of two homologues of fasd2 genes in common carp. The data showed that fads2b played a more important role in HUFA synthesis through both expression and functional analyses.

Effect of Protease Combined with Heat Treatment on the Volatile Composition and Aroma Quality in Liqueur Wine.

The aim of this paper was to compare the effects of two clarification methods, protease combined with heat treatment and bentonite, on the aroma quality of liqueur wines, and to identify and analyze the overall differences between the basic components and volatile aroma compounds of liqueur wines after the two treatments by chemical analysis, headspace-solid-phase microextraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS), and orthogonal partial least squares discriminant analysis (OPLS-DA). The results showed that total acidity, volatile acidity and pH in liqueur wines after protease combined with heat treatment were not significantly different from those of the blank control, and the ability to remove proteins was equal to that of the bentonite treatment. A total of 58 volatile aroma compounds were detected by HS-SPME-GC/MS. Compared with the blank control group (44 species, total 108.705 mg/L), 52 (83.233 mg/L) and 50 (120.655 mg/L) aroma compounds were detected in the bentonite and protease combined with heat treatments, respectively. Compared with the control and bentonite treatment, the protease combined with heat treatment significantly increased the total content of aromatic compounds in liqueur wines, and the types and contents of olefins, furans and phenols were higher. Among them, the compounds with major contributions in the protease combined with heat treatment were ionone, ß-damascenone, 3-methyl-1-butanol, alpha-terpineol and limonene, which helped increase the content of terpenoids and enhance the floral and fruit aroma of the wine. Meanwhile, linalool, diethyl succinate, 2-methyl-3-heptanone, butanal diethyl acetal, hexanal and n-octanol were six compounds with high content of aromatic compounds unique to liqueur wines after protease combined with heat treatment. The sensory evaluation results were consistent with the results of aromatic compound detection, and the overall quality was better. The results may provide a reference for further exploration of protease-based clarifiers suitable for liqueur wines.

Optimizations of optical chaos in semiconductor lasers based on multiobjective genetic algorithms.

We investigated the frequency bandwidth, autocorrelation function, and complexity of chaotic temporal waveforms in unidirectionally coupled semiconductor lasers with time-delayed optical feedback. The effective bandwidth, peak value of autocorrelation function, and maximum Lyapunov exponent were simultaneously optimized by searching several control parameters of the laser systems based on multiobjective genetic algorithms. We found a conflicting relation between the effective bandwidth enhancement and the time-delay signature suppression, and a detailed relationship between the maximum Lyapunov exponent and the peak value of autocorrelation function.

Limited-stage small cell carcinoma of the esophagus treated with curative esophagectomy: A multicenter retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors. METHODS: We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses. RESULTS: A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061). CONCLUSIONS: Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.

Real-time and simultaneous assay of monophenolase and diphenolase activity in tyrosinase catalyzed cascade reactions by combination of three-way calibration and excitation-emission matrix fluorescence.

A real-time assay for multiple enzyme activities in cascade reactions is required for research on metabolism and bioengineering. Tyrosinase has the bifunctional activity of monophenolase and diphenolase. A combined strategy of three-way calibration with excitation-emission matrix (EEM) fluorescence was developed for real-time and simultaneous determination of monophenolase and diphenolase activity with tyrosine as a substrate. Mathematical separation and second-order advantage were utilized to solve spectral overlapping and uncalibrated interferents during complex dynamic enzymatic processes. Kinetic evolution profiles of EEM were monitored to stack a fusion three-way data array together with static samples. Using a parallel factor analysis (PARAFAC) algorithm, pseudo-univariate calibration curves with limits of detection (LODs) of 3.00 µM and 0.85 µM were established to simultaneously and real-time measure tyrosine and DOPA. Progress curves for tyrosine consumption by monophenolase and DOPA consumption by diphenolase were obtained using the law of mass conservation to calculate the initial velocity. The LODs for monophenolase and diphenolase were 0.0232 U⋅mL-1 and 0.0316 U⋅mL-1. The method achieved real-time and simultaneous assays of multiple enzyme activities in cascade reactions. It showed potential application in the metabolic pathway and biochemical industry.

Comparison of the Safety and Efficacy of Three-Dimensional Guiding Templates and Free Hand Technique for Cervical Pedicle Screw Fixation: A Retrospective Study.

Aim. To compare the safety and efficacy of computed tomography (CT)-assisted three-dimensional guiding templates (3DGTs) and free-hand (FH) technique for posterior cervical pedicle screw fixation in cervical spondylotic myelopathy (CSM) treatment. Methods. Thirty-five patients (216 screws) with CSM and developmental cervical stenosis were randomly divided into groups A (FH) and B (3DGTs). All patients underwent modified posterior surgery with cervical pedicle screw insertion (C1-7). Preoperative, postoperative, and intergroup comparisons of efficacy were evaluated using the visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Short Form 12 (SF-12) scores and JOA score improvement rate. Incidence of intra- and postoperative complications was analyzed. Postoperative cervical spine CT was performed to evaluate (i) the pedicle screws' deviation angle from the optimal path (sagittal deviation, α; coronal deviation angle, ß), screw insertion point's deviation distance (d), and screw accuracy and (ii) the deviation angle and distance of screw entrance point of pedicle screws from the optimal channel. Results. All patients successfully completed the procedures. Groups A and B did not significantly differ in age, sex ratio, body mass index, operative time, or intraoperative blood loss amount. Postoperative VAS, JOA, and SF-12 scores improved in both groups. VAS, JOA, or SF-12 scores did not significantly differ between the 2 groups. The α, ß, and d scores were lower in group B, but accuracy was higher in group B. Conclusions. 3DGTs and FH technique show comparable outcomes with respect to neurological improvement and safety.

Dominant Elongase Activity of Elovl5a but Higher Expression of Elovl5b in Common Carp (Cyprinus carpio).

Most diploid freshwater and marine fish encode one elovl5 elongase, having substrate specificity and activities towards C18, C20 and C22 polyunsaturated fatty acids (PUFAs). The allo-tetraploid common carp is hypothesized to encode two duplicated elovl5 genes. How these two elovl5 genes adapt to coordinate the PUFA biosynthesis through elongase function and expression divergence requires elucidation. In this study, we obtained the full-length cDNA sequences of two elovl5 genes in common carp, named as elovl5a and elovl5b. Functional characterization showed that both enzymes had elongase activity towards C18, C20 and C22 PUFAs. Especially, the activities of these two enzymes towards C22 PUFAs ranged from 3.87% to 8.24%, higher than those in most freshwater and marine fish. The Elovl5a had higher elongase activities than Elovl5b towards seven substrates. The spatial-temporal expression showed that both genes co-transcribed in all tissues and development stages. However, the expression levels of elovl5b were significantly higher than those of elovl5a in all examined conditions, suggesting that elovl5b would be the dominantly expressed gene. These two genes had different potential transcriptional binding sites. These results revealed the complicated roles of elovl5 on PUFA synthesis in common carp. The data also increased the knowledge of co-ordination between two homoeologs of the polyploid fish through function and expression divergence.

The emerging role of miR-128 in musculoskeletal diseases.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field.

Diffusion kurtosis imaging detects the time-dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease.

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments.

A Metallic Ion-Induced Self-Assembly Enabling Nanowire-Based Aerogels.

The controlled assembly of nanowires is one of the key challenges in the development of a range of functional 3D aerogels with unique physicochemical properties for practical applications. However, the deep understanding of the dynamic assemble process for fabricating nanowire aerogels remains elusive. Herein, a facile strategy is presented for the metallic ion-induced assembly of nanowires into macroscopic aerogels via a solution-based process. This method enables the interconnecting between polymer-decorated nanowires via metallic coordination, resulting in plenty of nanowire bundles with the same orientation. Besides, the coordinated binding strength of nanowires with different metallic ions is also discussed. The assembly mechanism that the metallic ions induced dynamic behavior of nanowires is revealed via molecular dynamics theoretical evaluation. These findings benefit for constructing nanowire-based aerogels with unique structural features and multi-function, which pave new opportunities for other material systems.

Prognostic Role of Nodal Skip Metastasis in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study.

BACKGROUND: Nodal-skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), but its prognostic role is controversial. This study aimed to investigate the prognostic value of NSM for thoracic ESCC patients. METHODS: Categorization of NSM was according to the N groupings of Japan Esophagus Society (JES) staging system, which is dependent on tumor location. Using the Kaplan-Meier method and Cox-regression analysis, this study retrospectively analyzed the overall survival (OS) for 2325 ESCC patients after radical esophagectomy at three high-volume esophageal cancer centers. Predictive models also were constructed. RESULTS: The overall NSM rate was 20% (229/1141): 37.4% in the in upper, 12.9% in the middle, and 22.2% in the lower thoracic ESCC. The patients with NSM always had a better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (hazard ratio [HR], 0.633; 95% confidence interval [CI], 0.499-0.803; P < 0.001). By integrating the prognostic values of NSM and N stage, the authors proposed the new N staging system. The categories defined by the new N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the new N system was shown to be an independent prognostic factor also for thoracic ESCC patients (HR, 1.607; 95% CI, 1.520-1.700; P < 0.001). Overall, the new N system had slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the current N system. CONCLUSIONS: This study emphasized the prognostic power of NSM and developed a modified node-staging system to improve the efficiency of the current International Union for Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) N staging system.

Real-time fluorometric monitoring of monophenolase activity using a matrix-matched calibration curve.

Tyrosinase is the key enzyme for the metabolism of tyrosine and inherently comprises both monophenolase activity and diphenolase activity. A real-time fluorometric assay method was established to exclusively monitor the monophenolase activity by eliminating interference from diphenolase reactions through a combination of borate and hydroxylamine. Synthetic matrices comprised of tyrosine and DOPA (L-3,4-dihydroxyphenylalanine) preincubated with tyrosinase with the consistent sum concentration of 70 µM to mimic the monophenolase reaction mixture in borate buffer according to law of mass conservation. A matrix-matched calibration curve for determination of tyrosine was established using the synthetic matrices as standard sample to eliminate spectral interference from DOPA. The limit of detection (LOD) for tyrosine was 0.61 µM. The time course for consumption of tyrosine was established to measure the initial velocity through real-time reading out the tyrosine fluorescence intensity of the reaction mixture in a cuvette in situ. The assay worked in the monophenolase activity range from 0.2839 to 1.7308 U mL-1 with LOD of 0.0851 U mL-1. The proposal sensing system successfully afforded a prospective potential for application in enzyme kinetics and screening of inhibitor. Graphical abstract.