Ca2+ -independent transmission at the central synapse formed between dorsal root ganglion and dorsal horn neurons.

A central principle of synaptic transmission is that action potential-induced presynaptic neurotransmitter release occurs exclusively via Ca2+ -dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+ -independent but voltage-dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here, we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons in vitro, (i) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (ii) CiVDS-mediated EPSCs are independent of extracellular and intracellular Ca2+ ; (iii) CiVDS is faster than CDS in vesicle recycling with much less short-term depression; (iv) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity-induced EPSCs is mediated by CiVDS in a central synapse.

Irradiation-induced exosomal HMGB1 to confer radioresistance via the PI3K/AKT/FOXO3A signaling pathway in ESCC.

BACKGROUND: Radioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells. METHODS: Plasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group. RESULTS: The expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX. CONCLUSION: These findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.

Ca2+-independent but voltage-dependent quantal catecholamine secretion (CiVDS) in the mammalian sympathetic nervous system.

Action potential-induced vesicular exocytosis is considered exclusively Ca2+ dependent in Katz's Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. Here, by combining multiple independent recordings, we report that [1] CiVDS robustly presents in the sympathetic nervous system, including sympathetic superior cervical ganglion neurons and slice adrenal chromaffin cells, [2] uses voltage sensors of Ca2+ channels (N-type and novel L-type), and [3] contributes to catecholamine release in both homeostatic and fight-or-flight like states; [4] CiVDS-mediated catecholamine release is faster than that of Ca2+-dependent secretion at the quantal level and [5] increases Ca2+ currents and contractility of cardiac myocytes. Together, CiVDS presents in the sympathetic nervous system with potential physiological functions, including cardiac muscle contractility.

Insights into activated sludge/Chlorella consortia under dark condition compared with light condition.

Bacteria-algae consortia in the light bring the benefit of O2 production and CO2 reduction for wastewater treatment, while the bottleneck for application is how it behaves in the dark. In this study, inoculum ratio and sludge retention time (SRT) affected nutrient removal rather than chemical oxygen demand (COD) removal. Dark conditions (with a sludge/Chlorella inoculum ratio of 1:2 at a SRT of 15 d) achieved comparable performance to those of light conditions, due to bacteria contribution and mechanical aeration. Compared with light conditions, the ratio of Chla/Chlb decreased and Caro/(Chla + Chlb) increased to response oxidative stress. In the dark, algae were associated with Nitrosomonas and Dechloromonas. Flavobacterium disassociated with Chlorella in the dark but associated with Chlorella in the light. Moreover, nitritation genes (amo and Hao) and denitrifying gene (narH) were up-regulated, while P metabolism genes (PPX and PPK) were down-regulated. It is proposed to enrich Nitrosomonas in the night and denitrify polyphosphate accumulating organisms (DPAO) in the daytime to establish short-cut nitrification and denitrifying phosphorus removal in practical applications.

Lattice complex assembled by noncompetitive anti-EGFR antibodies regulates actin cytoskeletal reorganization.

BACKGROUND: Recent evidence of clinical trials highlights that the combination of two noncompetitive anti-EGFR antibodies can benefit patients with several cancers. Previous studies propose that a lattice complex assembled by antibodies and EGFR down-regulates surface EGFR by rapid internalization of the complex. However, there remains a paucity of evidence and understanding on the existence of a lattice complex on cell surface and its cellular processes of internalization. METHODS: Herein, we used three dimensions structured illumination microscopy to directly observe the actual morphology of the lattice complex formed on Hela cell membrane after noncompetitive anti-EGFR antibody combinations, and we explored the internalized mechanism of noncompetitive antibody combinations by constructing a PIP2 consumption system. RESULT: We observed the lattice complex (length > 1 µm) on the surface of living cell after preincubation with Cetuximab and H11, but combination of Cetuximab and single domain antibody 7D12 fails to assemble the lattice, these results demonstrates the importance of symmetrical structure of conventional antibody for lattice formation. Interestingly, the lattice complex assembles along with cytoskeletal fibers, and its internalization recruits a large amount of PIP2 and triggers the rearrangement of F-actin. CONCLUSIONS: The above data suggests that large-size lattice complex affects membrane fluidity and dynamic reorganization of cytoskeletal, which may be responsible for its rapid internalization. These new insight will aid in current rational combination design of anti-EGFR antibodies.

Allelochemicals-mediated interaction between algae and bacteria: Direct and indirect contact.

Secondary metabolites with bioactivity are allelochemicals. This study adopted direct contact (R0) and indirect contact (separated by 0.45 µm membrane, R1-A for algae, R1-S for sludge) to reveal the role of metabolites especially allelochemicals on interaction of bacteria and algae. Direct contact exhibited better nutrients removal than indirect contact, due to less antibacterial allelochemicals and oxidative stress. Bacterial signaling molecules were not detected. The major algae-derived allelochemicals were 13-Docosenamide, 9-Octadecenamide, n-Hexadecanoic acid, erucic acid, octadecanoic acid, ß-sitosterol, and E,E,Z-1,3,12-Nonadecatriene-5,14-diol. Furthermore, presence of 13-Docosenamide and 9-Octadecenamide was associated with succession of Flavobacterium and suppression of nitrifying bacteria (Nitrosomonas, Ellin6067, and Nitrospira). Direct contact stimulated denitrifying bacteria Saccharimonadales and algae Scenedesmus, whereas indirect contact is friendly to Dechloromonas, Competibacter, nitrifying bacteria, algae Desmodesmus and Dictyosphaerium. This study highlights the essentiality of cell contact of bacteria-algae in establishing synergy, as cell contact mitigates antagonistic effect induced by metabolites.

Oxygen affinity and light intensity induced robust phosphorus removal and fragile ammonia removal in a non-aerated bacteria-algae system.

Non-aerated bacteria-algae system gaining O2 through photosynthesis presents an alternative for costly mechanical aeration. This study investigated oxygen supply and performance of nutrients removal at low and high light intensity (LL and HL). The results showed that P removal was high and robust (LL 97 ± 1.8 %, HL 95 % ± 2.9 %), while NH4+-N removal fluctuated dramatically (LL 66 ± 14.7 %, HL 84 ± 8.6 %). Oxygen generated at illumination of 200 µmol m-2 s-1, 6 h was sufficient to sustain aerobic phase for 2.25 g/L MLSS. However, O2 produced by algae was preferentially captured in the order of heterotrophic bacteria (HB), ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB). Oxygen affinity coupled with light intensity led to NOB suppression with stable nitrite accumulation ratio of 57 %. Free nitrous acid (FNA) and light stimulated the abundance of denitrifying polyphosphate accumulating organism (DPAO) of Flavobacterium, but with declined P-accumulating metabolism (PAM) of P release, P/C, K/P and Mg/P ratios. Flavobacterium and cyanobacteria Leptolyngbya, along with biologically induced CaP in extracellular polymeric substances was the key to robust P removal. AOB of Ellin6067 and DPAO of Flavobacteria offer a promising scenario for partial nitrification-denitrifying phosphorus removal.

Frequency tunable magnetostatic wave filters with zero static power magnetic biasing circuitry.

A single tunable filter simplifies complexity, reduces insertion loss, and minimizes size compared to frequency switchable filter banks commonly used for radio frequency (RF) band selection. Magnetostatic wave (MSW) filters stand out for their wide, continuous frequency tuning and high-quality factor. However, MSW filters employing electromagnets for tuning consume excessive power and space, unsuitable for consumer wireless applications. Here, we demonstrate miniature and high selectivity MSW tunable filters with zero static power consumption, occupying less than 2 cc. The center frequency is continuously tunable from 3.4 GHz to 11.1 GHz via current pulses of sub-millisecond duration applied to a small and nonvolatile magnetic bias assembly. This assembly is limited in the area over which it can achieve a large and uniform magnetic field, necessitating filters realized from small resonant cavities micromachined in thin films of Yttrium Iron Garnet. Filter insertion loss of 3.2 dB to 5.1 dB and out-of-band third order input intercept point greater than 41 dBm are achieved. The filter's broad frequency range, compact size, low insertion loss, high out-of-band linearity, and zero static power consumption are essential for protecting RF transceivers from interference, thus facilitating their use in mobile applications like IoT and 6 G networks.

Chemically Driven Sintering of Colloidal Cu Nanocrystals for Multiscale Electronic and Optical Devices.

Emerging applications of Internet of Things (IoT) technologies in smart health, home, and city, in agriculture and environmental monitoring, and in transportation and manufacturing require materials and devices with engineered physical properties that can be manufactured by low-cost and scalable methods, support flexible forms, and are biocompatible and biodegradable. Here, we report the fabrication and device integration of low-cost and biocompatible/biodegradable colloidal Cu nanocrystal (NC) films through room temperature, solution-based deposition, and sintering, achieved via chemical exchange of NC surface ligands. Treatment of organic-ligand capped Cu NC films with solutions of shorter, environmentally benign, and noncorrosive inorganic reagents, namely, SCN- and Cl-, effectively removes the organic ligands, drives NC grain growth, and limits film oxidation. We investigate the mechanism of this chemically driven sintering by systemically varying the Cu NC size, ligand reagent, and ligand treatment time and follow the evolution of their structure and electrical and optical properties. Cl--treated, 4.5 nm diameter Cu NC films yield the lowest DC resistivity, only 3.2 times that of bulk Cu, and metal-like dielectric functions at optical frequencies. We exploit the high conductivity of these chemically sintered Cu NC films and, in combination with photo- and nanoimprint-lithography, pattern multiscale structures to achieve high-Q radio frequency (RF) capacitive sensors and near-infrared (NIR) resonant optical metasurfaces.

Response of nutrient loss to natural erosive rainfall events under typical tillage practices of contour ridge system in the rocky mountain areas of Northern China.

Changes in natural rainfall characterized by heavy precipitation and high rainfall intensity would increase the risks and uncertainty of nutrients losses. Losses of nitrogen (N) and phosphorus (P) with water erosion from agriculture-related activities has become the principal nutrients resulting the eutrophication of water bodies. However, a little attention has been paid to the loss characteristic of N and P responding to natural rainfall in widely used contour ridge systems. To explore the loss mechanism of N and P in contour ridge system, nutrient loss associated with runoff and sediment yield was observed in in situ runoff plots of sweet potato (SP) and peanut (PT) contour ridges under natural rainfall. Rainfall events were divided into light rain, moderate rain, heavy rain, rainstorm, large rainstorm, and extreme rainstorm level, and rainfall characteristics for each rainfall level were recorded. Results showed that rainstorm, accounting for 46.27% of the total precipitation, played a destructive role in inducing runoff, sediment yield, and nutrient loss. The average contribution of rainstorm to sediment yield (52.30%) was higher than that to runoff production (38.06%). Rainstorm respectively generated 43.65-44.05% of N loss and 40.71-52.42% of P loss, although light rain induced the greatest enrichment value for total nitrogen (TN, 2.44-4.08) and PO4-P (5.40). N and P losses were dominated by sediment, and up to 95.70% of the total phosphorus and 66.08% of TN occurred in sediment. Nutrient loss exhibited the highest sensitivity to sediment yield compared to runoff and rainfall variables, and a significant positive linear relationship was observed between nutrient loss and sediment yield. SP contour ridge presented higher nutrient loss than that in PT contour ridge, especially for P loss. Findings gained in this study provide references for the response strategies of nutrient loss control to natural rainfall change in contour ridge system.

A novel DNA damage repair gene-related prognostic model for evaluating the prognosis and tumor microenvironment infiltration of esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to investigate the potential prognostic value of DNA damage repair genes (DDRGs) in esophageal squamous cell carcinoma (ESCC) and their relationship with immune-related characteristics. METHODS: We analyzed DDRGs of the Gene Expression Omnibus database (GSE53625). Subsequently, the GSE53625 cohort was used to construct a prognostic model based on least absolute shrinkage and selection operator regression, and Cox regression analysis was used to construct a nomogram. The immunological analysis algorithms explored the differences between the potential mechanism, tumor immune activity, and immunosuppressive genes in the high- and low-risk groups. Of the prognosis model-related DDRGs, we selected PPP2R2A for further investigation. Functional experiments were conducted to evaluate the effect on ESCC cells in vitro. RESULTS: A 5-DDRG (ERCC5, POLK, PPP2R2A, TNP1 and ZNF350) prediction signature was established for ESCC, stratifying patients into two risk groups. Multivariate Cox regression analysis showed that the 5-DDRG signature was an independent predictor of overall survival. Immune cells such as CD4 T cells and monocytes displayed lower infiltration levels in the high-risk group. Additionally, the immune, ESTIMATE, and stromal scores in the high-risk group were all considerably higher than those in the low-risk group. Functionally, knockdown of PPP2R2A significantly suppressed cell proliferation, migration and invasion in two ESCC cell lines (ECA109 and TE1). CONCLUSION: The clustered subtypes and prognostic model of DDRGs could effectively predict the prognosis and immune activity of ESCC patients.

NEK2 promotes esophageal squamous cell carcinoma cell proliferation, migration and invasion through the Wnt/ß-catenin signaling pathway.

OBJECTIVES: The NEK2 (never in mitosis gene A-related kinase 2), a serine/threonine kinase involved in chromosome instability and tumorigenesis. Hence, this study aimed to explore the molecular function of NEK2 in esophageal squamous cell carcinoma (ESCC). METHODS: By available transcriptome datasets (GSE53625 cohort, GSE38129 cohort, and GSE21293 cohort), we analyzed the differentially expressed genes in invading and non-invading ESCC. Subsequently, we evaluated the association between NEK2 expression level and clinical outcomes through Kaplan-Meier analysis method. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) analyses were performed to determine the expression levels of NEK2 mRNA and protein, respectively. We knocked down the NEK2 expression in ESCC cells (ECA109 and TE1), and evaluated the NEK2 biology function associated with ESCC cell proliferation, migration, invasion, and colony formation abilities. Finally, the downstream pathway of NEK2 was analyzed through Gene Set Enrichment Analysis (GSEA) and validated the regulatory mechanism of NEK2 on the potential pathway through WB. RESULTS: We found that NEK2 was highly expressed in ESCC cells compared with human esophageal epithelial cells (HEEC) (P < 0.0001), and high NEK2 expression was remarkably associated with poor survival (P = 0.019). Knockdown of NEK2 showed the significant inhibitory effect for tumorigenesis, and suppressed the ESCC cells proliferation, migration, invasion, and formation of colonies abilities. Additionally, GSEA revealed that Wnt/ß-catenin pathway was a downstream pathway of NEK2. WB results further validated the regulatory mechanism of NEK2 for Wnt/ß-catenin signaling. CONCLUSIONS: Our results indicated that NEK2 promotes ESCC cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. NEK2 could be a promising target for ESCC.

City classification for municipal solid waste prediction in mainland China based on K-means clustering.

Cities in mainland China are usually classified according to geographical locations. This traditional city classification system is limited to relative fixed factors, which lives out a gap in terms of the spatial differences of municipal solid waste (MSW). Developing a more comprehensive city classification system is essential for MSW generation prediction and waste management. In this study, six economic, social and climatic indicators that affect MSW generation: population, per capita GDP (PCGDP), environmental sanitation investment (ESI), average temperature, average precipitation, and average humidity, are selected. Weights were calculated for each indicator using a combination of CRITIC weight method and Pearson correlation coefficient prior to cluster analysis. The k-means clustering algorithm was used to classify all cities into four clusters, which differed significantly in the relationships between MSW generation and influencing factors. The results of Kruskal-Wallis test also show that cities in different clusters show different distributions in terms of the indicators selected. The cross-prediction results of the model further validate the reliability of the clustering results from a quantitative perspective. By establishing a city classification system, cities with similar relationships between MSW generation and influencing factors can be placed into one cluster. The model established in one certain city cluster can be used to predict the MSW generation for cities in the same cluster that lack historical data. This may also help to formulate appropriate regional policies according to different relationships between MSW generation and influencing factors, especially for the four city clusters in the mainland China.

HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC.

Esophageal cancer is a common malignant disease that is generally treated with radiotherapy. High mobility group box 1 (HMGB1) plays an essential role in tumor cell proliferation, migration, and cell cycle progression. Here, we aimed to clarify the effects of HMGB1 on radioresistance in esophageal squamous cell carcinoma (ESCC) cell lines and patient survival. We performed immunohistochemistry for HMGB1 in biopsy samples of 39 stage I-III ESCC patients grouped by HMGB1 expression status. Then, 1-, 3-, 5-, and 10-year overall survival outcomes were calculated by Kaplan-Meier survival analysis. The cellular localization of HMGB1 was examined before and after irradiation by Immunofluorescence staining. Stable cell lines (KYSE30 and KYSE510) with differential HMGB1 expression were constructed using lentiviruses. Furthermore, we examined phosphorylated histone H2AX (γ-H2AX) expression in both HMGB1 overexpression and negative control groups by western blotting. HMGB1-negative expression was associated with superior ESCC patient 10-year survival (P=0.016). HMGB1 overexpression promoted cell migration, proliferation, and radioresistance and mitigated cell cycle arrest at the G0/G1 phase induced by irradiation. This demonstrates that HMGB1-positive expression is correlated with unfavorable clinical outcomes, and HMGB1 overexpression may promote the malignant phenotype of ESCC cells and induce radioresistance by regulating cell cycle distribution in ESCC.

Novel nomograms predicting the survival of patients with nonsurgical thoracic esophageal squamous cell carcinoma treated with IMRT: A retrospective analysis.

The purpose of this study was to evaluate several preradiotherapy serum inflammatory indicators, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation score (SIS), and compare which of these indicators had the highest value in predicting survival. Inflammatory markers were combined with traditional prognostic factors, and novel nomogram models were developed to predict overall survival (OS) and progression-free survival (PFS) for patients with esophageal squamous cell carcinoma. A total of 245 patients were enrolled. The Kaplan-Meier method and univariate and multivariate analyses were used to compare survival differences. A total of 239 patients met the eligibility criteria. The survival numbers at 1, 3, and 5 years were 176, 83, and 62, respectively. The OS and PFS rates estimated at 1, 3, and 5 years were 74.6%, 36.8%, and 26.5% and 58.4%, 31.3%, and 20.5%, respectively. The differences in patients' OS and PFS were significant when univariate analysis was applied based on inflammation-based measures. Multivariate analysis showed that tumor length, tumor stage, tumor/node/metastasis stage, chemotherapy, and SIS value were predictive variables for OS and PFS. The nomogram model established based on the multivariate models of the training data set had good predictive ability. The unadjusted C-index was 0.701 (95% CI, 0.662-0.740) and 0.695 (95% CI, 0.656-0.734) for OS and PFS, respectively. This study showed that the SIS-based nomogram could accurately predict the OS and PFS of patients with esophageal squamous cell carcinoma.

Three-Dimensional Holey Graphene Enwrapped Li3 V2 (PO4 )3 /N-Doped Carbon Cathode for High-Rate and Long-Life Li-Ion Batteries.

Monoclinic Li3 V2 (PO4 )3 is a promising cathode material for high-power Li-ion batteries. Herein, a three-dimensional holey graphene enwrapped Li3 V2 (PO4 )3 /N-doped carbon (LVPNCHG) nanocomposite has been successfully synthesized. The holes could be in-situ and directly introduced in graphene through H2 O2 chemical etching in the synthesis process, which could remarkably enhance the ion and electron transport and greatly improve the electrochemical performance of the LVPNCHG electrode: 78 mAh g-1 at 150 C, 86.1 % capacity retention over 2000 cycles at 10 C, and 96 % capacity retention over 500 cycles at 1 C under -20 °C. Moreover, in-situ distribution of relaxation time analysis was used to study LVPNCHG cathode during charge/discharge at 3.0-4.8 V, combined with in-situ X-ray diffraction measurement, and the results showed that a two-phase reaction mechanism was involved during the insertion of Li+ in the discharge process. Further demonstration of graphite//LVPNCHG full cell indicated great potential of the as-synthesized materials for practical application.

Combining the systemic inflammation response index and prognostic nutritional index to predict the prognosis of locally advanced elderly esophageal squamous cell carcinoma patients undergoing definitive radiotherapy.

Background: The systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) have been shown to be correlated with the prognosis of various solid tumors. This study sought to investigate the prognostic value of the SIRI and the PNI individually and in combination in locally advanced elderly esophageal squamous cell carcinoma (ESCC) patients treated with radical radiotherapy. Methods: The data of 192 ESCC patients aged ≥65 years, who had been treated with definitive radiotherapy between 2013 and 2016, were retrospectively analyzed. The optimal cutoff values of SIRI and PNI were determined by receiver operating characteristic curves. Kaplan-Meier curves and Cox proportional hazards models were used to analyze the effect of the SIRI and PNI on overall survival (OS) and progression-free survival (PFS). The areas under the curve were measured to evaluate the predictive ability of the SIRI, PNI, and SIRI combined with PNI for OS. Results: The optimal cutoff values of the pretreatment SIRI and PNI were 1.03 and 49.60, respectively. The univariate and multivariate analyses demonstrated that T stage (P=0.021), TNM stage (P=0.022), synchronous chemotherapy (P=0.032), the SIRI (P=0.001), and the PNI (P=0.045) were independent prognostic factors for OS and N stage (P=0.004), synchronous chemotherapy (P=0.016) and the SIRI (P=0.004) were independent prognostic factors for PFS. The AUC of the combined SIRI and PNI (0.706; 0.612-0.801) was higher than those of the SIRI (0.648; 0.540-0.756) and the PNI (0.621; 0.523-0.720). Patients in the low-SIRI and high-PNI groups, especially those in clinical stage II or who received synchronous chemotherapy (P<0.001, P=0.002), had better OS and PFS than those in the other groups (P<0.001). Conclusions: The SIRI and PNI are simple and reliable biomarkers for predicting long-term survival in elderly patients with locally advanced ESCC after radical radiotherapy. A high SIRI and a low PNI indicated poor prognosis, and the combination of the SIRI and PNI improved the accuracy of prognosis prediction and could be used to guide individualized treatment of patients.

Tuning the Size of Large Dense-Core Vesicles and Quantal Neurotransmitter Release via Secretogranin II Liquid-Liquid Phase Separation.

Large dense-core vesicles (LDCVs) are larger in volume than synaptic vesicles, and are filled with multiple neuropeptides, hormones, and neurotransmitters that participate in various physiological processes. However, little is known about the mechanism determining the size of LDCVs. Here, it is reported that secretogranin II (SgII), a vesicle matrix protein, contributes to LDCV size regulation through its liquid-liquid phase separation in neuroendocrine cells. First, SgII undergoes pH-dependent polymerization and the polymerized SgII forms phase droplets with Ca2+ in vitro and in vivo. Further, the Ca2+ -induced SgII droplets recruit reconstituted bio-lipids, mimicking the LDCVs biogenesis. In addition, SgII knockdown leads to significant decrease of the quantal neurotransmitter release by affecting LDCV size, which is differently rescued by SgII truncations with different degrees of phase separation. In conclusion, it is shown that SgII is a unique intravesicular matrix protein undergoing liquid-liquid phase separation, and present novel insights into how SgII determines LDCV size and the quantal neurotransmitter release.

Effects of preoperative radiotherapy on survival of patients with stage II and III esophageal squamous cell carcinoma: A population-based study.

ABSTRACT: The impact of preoperative radiotherapy (PRT) on survival in patients with stage II and III esophageal squamous cell carcinoma (ESCC) remains controversial. The aim of this study was to explore the effect of PRT on survival of these patients.Patients with stage II and III ESCC who underwent chemotherapy ± PRT were identified and retrieved from the SEER database from 2010 to 2015. Cox regression analysis was used to identify independent prognostic factors in patients. Subgroup analysis stratified by T stage and N stage was performed. Kaplan-Meier survival analysis was performed to assess disease specific survival (DSS).A total of 1160 patients were retrieved, of whom 289 (24.9%) underwent PRT plus chemotherapy, and 871 (75.1%) did not receive PRT. In multivariate analysis, PRT plus chemotherapy was a favorable prognostic factor for patients with stage T2 (hazard ratio [HR], 0.364, 95% CI, 0.202-0.658; P < .001), T3 (HR, 0.536, 95% CI, 0.413-0.695; P < .001) and T4 (HR, 0.318, 95% CI, 0.125-0.805; P = .016), but PRT plus chemotherapy was not statistically significant on DSS in patients with T1 disease (HR, 0.556, 95% CI, 0.262-1.179; P = .126). All 3 different N stages (N0, N1, and N2 + N3) were statistically significant (P < .05) in chemotherapy with or without PRT.In conclusion, patients with stage II and III ESCC at the T2-T4 stage gained significant survival benefit from PRT plus chemotherapy.

Highly efficient polyethylene glycol-functionalised gold nanorods for photothermal ablation of hepatocellular carcinoma cells.

Gold nanorods (GNRs) with exceptional photothermal properties have held promising potential for application in the biomedical field. In this study, the authors achieved photothermal ablation by polyethylene glycol (PEG)-functionalised GNRs. Well-dispersed and uniform GNRs were produced through a seed-mediated growth method. A thermal camera was used to scrutinise the temperature distribution and efficiency of the photothermal properties of the GNRs, which were irradiated by an 808 nm laser on a silicon chip. They observed that the GNRs provided about a 5°C temperature increase and produced hyperthermia efficiently. Since GNRs need to be surface tailored with a biocompatible material rather than cetyltrimethylammonium bromide (CTAB), they chose methoxyl PEG thiol to modify the GNRs. By taking advantage of the alkaline environment that assists this functionalisation, they accomplished about 89% removal of CTAB and identified a PEG layer on the surface of the GNRs. The GNR biocompatibility was considerably improved without any shift of the optical properties. Hepatocellular carcinoma cells were incubated with GNRs for 24 h and then were irradiated with a near-infrared laser for 3 min. Few cells remained alive, which demonstrated the photothermal ablation ability of the GNRs.