Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer.

Colorectal cancer (CRC) is a form of cancer that is often resistant to chemotherapy, targeted therapy, radiotherapy, and immunotherapy due to its genomic instability and inflammatory tumor microenvironment. Ferroptosis, a type of non-apoptotic cell death, is characterized by the accumulation of iron and the oxidation of lipids. Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells. Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance. Moreover, the gut, responsible for regulating iron absorption and release, could influence CRC susceptibility through iron metabolism modulation. Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management, potentially revolutionizing treatment approaches for therapy-resistant cancers.

HKDC1 enhances the proliferation, migration and glycolysis of pancreatic adenocarcinoma and is linked to immune infiltration.

Background: Understanding the molecular mechanisms of pancreatic adenocarcinoma (PAAD) development is vital for treating this disease, as the current prognosis and treatment options are highly discouraging. Objective: This study aimed to examine the involvement of Hexokinase Domain Containing 1 (HKDC1) in the progression of PAAD. Methods: The study utilized bioinformatics techniques to evaluate the relationship between the expression of HKDC1 and clinical characteristics. In vitro experiments were conducted to investigate the molecular mechanisms and biological functions of HKDC1 in PAAD. Results: The findings of this research indicate that the expression of HKDC1 was increased in various types of human cancers, and a significant correlation was observed between elevated HKDC1 expression in PAAD and unfavorable prognosis. According to the findings from univariate and multivariate Cox regression analyses, HKDC1 could potentially serve as a standalone prognostic indicator for individuals diagnosed with PAAD. After performing calculations, we determined that the HKDC1 high-expression group exhibited lower immunologic score and higher ESTIMATE score, indicating a difference in immune infiltration score. In order to validate the expression of HKDC1 in PAAD cell lines, we analyzed the PAAD cell lines through qPCR and protein blotting. The expression of HKDC1 in human PAAD tissues was also detected by western blotting. Additionally, we explored the involvement of HKDC1 in PAAD by conducting experiments such as colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, and wound healing assays. In our study, we discovered that disruption of HKDC1 expression in PAAD cell types resulted in a decrease in cell growth rate and inhibited cell movement and invasion. Conclusion: To conclude, our findings indicate that HKDC1 has a significant impact on the tumor microenvironment (TME) of PAAD and could potentially be a promising target for PAAD treatment, offering fresh perspectives on the management of PAAD.

Multiple independent origins of duplicated mitochondrial control regions indicate an apomorphy in the Thysanoptera (Insecta).

The mitochondrial genome (mitogenome) of thrips is characterized by the presence of control region (CR) duplication. However, the evolution pattern of duplicated CRs in thrips is still unclear. In this study, the multiple independent origins of duplicated CR indicated that the CR duplication was not an ancestral state for Thysanoptera. The macroevolutionary pattern suggested that the earliest CR duplication event occurred in the middle Cretaceous (94.85 Ma) coincided with rearrangement events forming the ancestors of Aeolothripidae, but much later than that forming the ancestors of the suborder Terebrantia. The mitogenome with duplicated CRs showed a higher rate of gene rearrangement. The sequence similarity of the CR copies and divergence time were negatively correlated, indicating age-related deterioration of mitochondrial function. No significant differences were found in the mitochondrial DNA, the P123 and P4FD between the single and multiple-CR charactered mitogenomes, which suggested that the duplicated CRs may not affect the replication process in thrip mitogenome. The mitogenomes with duplicated CRs (mean: 0.0088 subs/s/my) show a significantly increased evolutionary rate than that with a single one (mean: 0.0058 subs/s/my). However, it seems that this higher evolutionary rate did not have adaptive mechanisms in Terebrantia. We speculated that the duplicated CRs may cause a more intense production of energy by mitochondria, and an accelerated mutation and substitution rate is expected in such mitogenomes. Our study provided new insights into the presence of CR duplications and their evolution in the mitogenomes of thrips.

Promising lanthanide-doped double molybdates KYb(MoO4)2 phosphors for highly efficient upconversion luminescence and temperature sensing.

Here we report the highly efficient upconversion luminescence (UCL) and optical temperature sensing based on the novel host of KYb(MoO4)2 doped with trivalent lanthanide (Ln3+) ions at 980 nm excitation. The high Yb3+ concentration and unique ordered layer structure in KYb(MoO4)2 host are beneficial for the enhancement of UCL efficiency by improving the absorption and the negative migration of excitation energy. Ho3+, Er3+, and Tm3+ ions were selected to singly dope the KYb(MoO4)2 host, achieving three primary colors of red, green, blue UCL, respectively. At the optimal doping concentration, the blue upconversion quantum yield (UCQY) of the KYb(MoO4)2: 1.0%Tm3+ phosphor reaches 0.13%, which is rare for the Tm3+-doped oxides. By leveraging the efficient blue light, we achieved high-brightness white UCL by co-doping Ho3+ in KYb(MoO4)2: Tm3+. Furthermore, the temperature sensing performance of the KYb(MoO4)2: Tm3+, Ho3+ phosphors operating within the first biological window (BW-I) was evaluated based on a thermo-responsive fluorescence intensity ratio (FIR) of far-red to near-infrared (NIR) emission from completely separated 3F2,3/3H4 → 3H6 transitions of Tm3+. At the excitation of 980 nm, the maximum absolute and relative sensitivities were determined as 0.25 × 10-3 K-1 at 673 K and 2.84% K-1 at 303 K, respectively. These results indicate that the double alkali-rare-earth molybdate KYb(MoO4)2 can be used as a promising host to achieve highly efficient UCL and temperature sensing, suggesting potential applications in the fields of anti-counterfeiting, displays, and non-contact temperature sensors.

Enhanced glucose homeostasis via Clostridium symbiosum-mediated glucagon-like peptide 1 inhibition of hepatic gluconeogenesis in mid-intestinal bypass surgery.

BACKGROUND: The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood. AIM: To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism. METHODS: Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor. RESULTS: The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota. CONCLUSION: The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.

Differences in metabolic improvement after metabolic surgery are linked to the gut microbiota in non-obese diabetic rats.

BACKGROUND: Different metabolic/bariatric surgery approaches vary in their effect on weight loss and glucose levels, although the underlying mechanism is unclear. Studies have demonstrated that the gut microbiota might be an important mechanism of improved metabolism after metabolic/bariatric surgery. AIM: To investigate the relationship between the improvement in metabolic disturbances and the changes in gut microbiota after gastric or intestinal bypass. METHODS: We performed sleeve gastrectomy (SG), distal small intestine bypass (DSIB) or sham surgery in nonobese rats with diabetes induced by 60 mg/kg streptozotocin (STZ-DM). RESULTS: The group comparisons revealed that both SG and DSIB induced a reduction in body weight and significant improvements in glucose and lipid metabolism in the STZ-DM rats. Furthermore, DSIB exhibited a stronger glucose-lowering and lipid-reducing effect on STZ-DM rats than SG. 16S ribosomal RNA gene sequencing revealed the gut abundance of some Lactobacillus spp. increased in both the SG and DSIB groups after surgery. However, the DSIB group exhibited a more pronounced increase in the gut abundance of Lactobacillus spp. compared to the SG group, with more Lactobacillus spp. types increased in the gut. CONCLUSION: The gut abundance of Lactobacillus was significantly correlated with the improvement in glycolipid metabolism and the change in serum fibroblast growth factor 21 levels.

MiR-30a-5p inhibits cell behaviors in esophageal cancer via modulating CBX2.

BACKGROUND: This investigation studied the impacts of the miR-30a-5p/CBX2 axis on esophageal cancer (EC). METHODS: Research objects were ascertained using The Cancer Genome Atlas database. Followed by qRT-PCR, western blot, dual-luciferase reporter, MTT, Transwell, and wound healing approaches, we tested gene expression and varying cell behaviors RESULTS: Conspicuously miR-30 family members (miR-30a-5p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-30e-5p) downregulation and CBX2 upregulation were discovered in EC cells. miR-30 family members target CBX2 and inhibited CBX2 expression. EC cell behaviors were inhibited by miR-30a-5p/CBX2 axis. CONCLUSION: MiR-30a-5p draws a new inspiration for EC treatment.

Association between perfluoroalkyl and polyfluoroalkyl substances exposure and fetal overgrowth: A prospective birth cohort study conducted in China.

BACKGROUND: Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been associated with gestational diabetes mellitus, obesity or overweight in childhood, but data on fetal overgrowth outcomes including macrosomia and large for gestational age (LGA) and among gestational age diverse infants remain scarce. OBJECTIVE: To evaluate the association between maternal PFASs exposure and macrosomia and LGA, with exploration of the interaction between PFASs exposure and gestational age on fetal overgrowth. METHODS: A total of 1441 mother-infants pairs from Guangxi Zhuang Birth Cohort of China were analyzed. Nine PFASs were measured in maternal serum using ultra-high liquid performance chromatographytandem mass spectrometry. Multivaraible logistical regression and generalized additive models were performed for individual PFAS exposures, piecewise regression analysis was used to estimate the breakpoint values for the non-linear dose-response relationships. Bayesian Kernel Machine Regression was performed for PFASs mixture. RESULTS: In single pollutant models, maternal PFDA and PFOA exposure showed U-shaped relationship with macrosomia and LGA. When PFDA concentration exceeded 0.32 ng/mL was significantly positively associated with risks of LGA and macrosomia (OR=4.66, 95%CI: 1.26, 17.17; OR=14.43, 95%CI: 2.64, 79.02; respectively), while a negatively association was observed when level below 0.32 ng/mL. When PFOA concentration exceeded 1.20 ng/mL was significantly associated with increased risk of macrosomia (OR=7.75, 95%CI: 1.36, 44.06). In mixed exposure models, mixture of PFASs was positively associated with macrosomia, as well as associated with LGA when all the PFASs were at their 30th percentile or below. The maximum risk of LGA was reached when concentrations of PFUnA, PFDA, or PFBS were at the highest concentrations and the gestational age at the minimum of this study. CONCLUSIONS: Maternal exposure to PFDA, PFOA and PFASs mixture were non-monotonically associated with macrosomia and LGA, the direction of the associations depends on the level of exposure.

Interobserver Variations in Target Delineation in Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma and its Impact on Target Dose Coverage.

BACKGROUND: To investigate the differences between physicians in target delineation in intensity-modulated radiation therapy for nasopharyngeal carcinoma as well as their impact on target dose coverage. METHODS: Ninety-nine in-hospital patients were randomly selected for retrospective analysis, and the target volumes were delineated by 2 physicians. The target volumes were integrated with the original plans, and the differential parameters, including the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Jaccard similarity coefficient (JSC) were recorded. The dose-volume parameters to evaluate target dose coverage were analyzed by superimposing the same original plan to the 2 sets of images on which the target volumes were contoured by the 2 physicians. The significance of differences in target volumes and dose coverage were evaluated using statistical analysis. RESULTS: The target dose coverage for different sets of target volumes showed statistically significant differences, while the similarity metrics to evaluate geometric target volume differences did not. More specifically, for PGTVnx, the median DSC, JSC, and HD were 0.85, 0.74, and 11.73, respectively; for PCTV1, the median values were 0.87, 0.77, and 11.78, respectively; for PCTV2, the median values were 0.90, 0.82, and 16.12, respectively. For patients in stages T3-4, DSC, and JSC were reduced but HD was increased compared to those in stages T1-2. Dosimetric analysis indicated that, for the target volumes, significant differences between the 2 physicians were found in D95, D99, and V100 for all the target volumes (ie, PGTVnx, PCTV1, and PCTV2) across the whole group of patients, as well as in patients with disease stages T3-4 and T1-2. CONCLUSIONS: The target volumes delineated by the 2 physicians had a high similarity, but the maximal distances between the outer contours of the 2 sets were significantly different. In patients with advanced T stages, significant differences in dose distributions were found, stemming from the deviations of target delineation.

Vanadium Hexacyanoferrate as a High-Capacity and High-Voltage Cathode for Aqueous Rechargeable Zinc Ion Batteries.

Prussian blue analogs (PBAs) are widely used as electrode materials for secondary batteries because of their cheapness, ease of synthesis, and unique structural properties. Nevertheless, the unsatisfactory capacity and cyclic stability of PBAs are seriously preventing their practical applications. Here, vanadium hexacyanoferrate (VHCF) is successfully prepared and used as a cathode for aqueous zinc-ion batteries (AZIBs). When using 3 M Zn(CF3SO3)2 as the electrolyte, a high capacity of ~230 mA h g-1 and a high voltage of ~1.2 V can be achieved. The XRD result and XPS analysis indicate that the outstanding Zn2+ storage capability is due to the presence of dual electrochemical redox centers in VHCF (Fe2+ ⇋ Fe3+ and V5+ ⇋ V4+ ⇋ V3+). However, the battery shows a short cycle life (7.1% remaining capacity after 1000 cycles) due to the dissolution of VHCF. To elongate the cycle life of the battery, a high-concentration hybrid electrolyte is used to reduce the activity of water molecules. The improved battery exhibits an impressive capacity of 235.8 mA h g-1 and good capacity retention (92.9%) after 1000 cycles.

Association of maternal perfluoroalkyl substance exposure with postpartum haemorrhage in Guangxi, China.

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (ß: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (ß: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage.

The Role of Bile Acid in Improving Glucose Tolerance of Non-Obese Diabetic Rats After Proximal Small Bowel Bypass.

An increase in bile acid (BA) levels after metabolic surgery is an important mechanism for improving glucose metabolism. However, the mechanisms underlying elevated BA levels and the regulatory mechanism of glucose metabolism remain unclear. In this study, we used the Goto-Kakizaki rat model to investigate the mechanism of BA elevation by comparing side-to-side jejunoileal bypass plus proximal loop ligation (SSJIBL) and bile ileum diversion (BID) as well as to explore the mechanism of BA metabolism in regulating blood glucose. The results showed that the fed blood glucose of rats in both the SSJIBL and BID groups was significantly lower than that of the SHAM group on days 2 and 14 after the operation. The oral glucose tolerance test (OGTT) improved in the SSJIBL and BID groups at day 14 postoperatively. The expression of CYP27A1 in the livers of the SSJIBL and BID groups was significantly increased. In addition, total serum BA levels in the SSJIBL and BID groups were significantly increased. Moreover, serum levels of lithocholic acid (LCA) and deoxycholic acid (DCA) were significantly higher in the SSJIBL group than in the SHAM group and negatively correlated with the area under the glucose tolerance curve (AUC-OGTT). In conclusion, increased BA synthesis may be an important cause of elevated total serum BA levels, and LCA and DCA are closely associated with improved glucose metabolism.

miR-3942-3p Increases the radiosensitivity of nasopharyngeal carcinoma through negatively regulating BARD1.

Nasopharyngeal carcinoma (NPC) has high incidence in China and East and Southeast Asia. The study was performed to investigate the effect of microRNA3942-3p (miR-3942-3p) on the radiosensitivity of NPC. Compared with non-cancer tissue, NPC had significantly lower miR-3942-3p expression. X-irradiation (IR) reduced the expression of miR-3942-3p in a dose-dependent way in NPC cells. Down-regulation of miR-3942-3p using miR-3942-3p inhibitor resulted in significantly increased cell viability, decreased apoptosis of CNE1 cells. Bax decreased and Bcl2 increased after IR. The expression of BARD1, a cancer predisposing gene, was elevated in NPC tissue. It was confirmed to be a target of miR-3942-3p using luciferase reporter assay. Down-regulation of BARD1 using siRNA significantly reduced cell viability and significantly increased apoptosis both before and after IR. The same response was observed when miR-3942-3p mimics was used to transfect BARD1-overexpressing CNE1 cells, suggesting the up-regulation of miR-3942-3p could sensitize CNE1 cells to X-rays via BARD1. Our data demonstrate that up-regulation of miR-3942-3p could sensitize NPC to X-rays via a downstream target BARD1, offering potential new strategies for radiotherapy of NPC.

Effects of household environmental exposure and ventilation in association with adverse birth outcomes: A prospective cohort study in rural China.

Prenatal exposure to outdoor air pollution have been associated with birth outcomes. However, there is limited evidence on the adverse effects of household indoor air pollution worldwide, much less in rural areas of China. This study aimed to explore the associations of household environmental factors (primary cooking fuel, housing renovation, and home ventilation) with four adverse birth outcomes (preterm birth (PTB), small for gestational age (SGA), low birth weight (LBW), and term low birth weight (T-LBW)). We conducted a cohort study involving 10,324 pregnancies in women who delivered a live-born infant from 2015 to 2018 in Guangxi, China. Risk ratios and 95% confidence intervals (CI) were estimated with control for reproductive history, lifestyle, home environmental confounders, and other potential confounders. A total of 5.4% of the infants were PTB, 10.7% were SGA, 5.5% had LBW, and 3.0% had T-LBW. Household-use induction cookers as the primary cooking fuel during pregnancy was associated with SGA (RR = 1.31, 95% CI: 1.07-1.60), LBW (1.41, 1.09-1.82), and T-LBW(1.62, 1.16-2.26), as compared with household-use gas as the primary cooking fuel. Housing renovation within one year before pregnancy was associated with PTB (1.45, 1.06-1.98) and LBW (1.56, 1.17-2.09), while housing renovation during pregnancy was associated with a higher risk of SGA only in moderate home ventilation conditions (3.74, 1.69-8.28). Our findings suggested that household-use induction cookers as the primary cooking fuel increased the risks of SGA, LBW, and T-LBW. In addition, housing renovation within one year before pregnancy increased the risks of PTB and LBW. Proper home ventilation may reduce the effect on the association between housing renovation during pregnancy and SGA.

Near-infrared-emitting upconverting BiVO4 nanoprobes for in vivo fluorescent imaging.

Near-infrared (NIR) emitting BiVO4:Yb3+,Tm3+ nanoparticles are synthesized by a new solvothermal strategy using solvents of oleic acid and methanol. The obtained BiVO4:Yb3+,Tm3+ samples show an average particle size of ≈164 nm and exhibit an asymmetry monoclinic crystal structure of BiVO4. At NIR excitation of 980 nm, the BiVO4:Yb3+,Tm3+ sample exhibits a nearly single NIR emission at ≈796 nm with extremely weak blue emissions from Tm3+ ions. These high-energy visible emissions are absorbed by the semiconducting host of BiVO4 that possesses a bandgap of ≈2.2 eV. Therefore, the NIR excitation to a single intense NIR emission fluorescent BiVO4 materials could be a potential ideal probe for deep-tissue high-resolution bioimaging. To validate the ability of BiVO4 materials for bio-applications, we conduct the cytotoxicity experiments. The results show that the cytotoxicity of HeLa cells is negligible at a concentration of 0.2 mg/ml of BiVO4:Yb3+,Tm3+ , and the cell viability approaches 90% at a high dosage of 0.5 mg/ml. The Daphnia magna and Zebrafish treated with nanoparticles (0.5 mg/ml) display bright NIR emission without any background, indicating the excellent in vivo fluorescent imaging capacity of BiVO4:Yb3+,Tm3+ nanoparticles. Our findings offer an environment-friendly strategy to synthesize BiVO4 UCL nanophosphors and provide a promising new class of fluorescent probes for biological applications.

Bypassing Different Parts of the Small Intestine Determines Different Metabolic Effects in Streptozotocin-Induced Diabetic Rats.

PURPOSE: Side-to-side jejunoileal bypass with proximal loop ligation (SSJIBL) has significant glucose-lowering and weight-control effects; however, no study has elucidated which segment is most effective in SSJIBL. This study investigated the effect of proximal small intestinal bypass (PSIB), middle small intestinal bypass (MSIB), and distal small intestinal bypass (DSIB) on metabolic improvement in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: STZ-induced diabetic rats were divided into four groups: PSIB, MSIB, DSIB, and sham-operated. The primary outcome measures were body weight, food intake, fasting blood glucose (FBG) levels, oral glucose tolerance (OGTT), insulin tolerance (ITT), serum insulin, gut hormones, serum lipid profile, and liver function levels. RESULTS: Global body weight in the DSIB group was lower than that in the PSIB group. The global food intake in the PSIB group was lower than that in the MSIB group. The PSIB group had a slightly better glucose-lowering effect than the MSIB and DSIB groups. The PSIB, MSIB, and DSIB groups all had improvement in insulin sensitivity at postoperative week 6. The MSIB group exhibited the best improvement in lipid homeostasis. Serum insulin and leptin levels were higher, and serum ghrelin levels were lower in the operated groups than in the sham group. CONCLUSIONS: This study provides experimental evidence that PSIB surgery induces a better glucose-lowering effect than DSIB surgery, and MSIB induced the best improvement in lipid homeostasis, whereas DSIB was even more advantageous in terms of weight control in the STZ-induced diabetic rat model.

Endostar, an Antiangiogenesis Inhibitor, Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer.

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

The Role of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Predicting Treatment Response for Cervical Cancer Treated with Concurrent Chemoradiotherapy.

PURPOSE: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting early treatment response. MATERIALS AND METHODS: Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) were enrolled. Pelvic DCE-MRI scans were performed before RT (pre-RT), in the middle of RT (mid-RT), and at the end of RT (post-RT), separately. Parameters (ie, Ktrans, Kep, and Ve) were measured. Pre-, mid-, and post-RT Ktrans were denoted as Ktrans-preTx, Ktrans-midTx, and Ktrans-postTx, respectively. And the same denoting rule also went for Kep and Ve. Difference for the same parameter such as Ktrans measured between two consecutive time points was calculated as second Ktrans value minus first Ktrans value. The differences in Ktrans between pre-RT and post-RT, between pre-RT and mid-RT, and between mid-RT and post-RT were denoted as ΔKtrans-post-preTx, ΔKtrans-mid-preTx, and ΔKtrans-post-midTx, respectively, and the same denoting rule was also applied to Kep and Ve. RESULTS: A total of 57 patients were enrolled. After the treatment, 31 patients had complete response (CR group). The remaining 26 patients had partial response (NCR group). Significant differences were found in Ktrans-postTx, Kep-postTx, Ve-midTx, ΔKtrans-post-preTx, ΔKtrans-post-midTx, ΔKep-post-preTx, ΔKep-mid-preTx and ΔKep-post-midTx between the two groups. Receiver operating characteristic (ROC) analysis for their performances in predicting treatment response showed an area under curve (AUC) of 0.656-0.849, sensitivity of 61.3-93.5%, specificity of 46.1-73.1%, and maximal Youden Index of 36.5-66.6. Among those parameters, Kep-postTx was the best, and its AUC, sensitivity, specificity, maximal Youden Index, and cutoff value were 0.849, 87.1%, 73.1%, 60.2, and 0.341, respectively. These combined parameters showed an AUC of 0.952, with sensitivity of 87.1%, specificity of 96.1%, and maximal Youden Index of 83.2. CONCLUSION: DCE-MRI parameters can predict early treatment outcome. Among those parameters, Kep-postTx is the best predictor. The combination of multi-parameters can increase the predictive potency.

High-Capacity and Long-Lifespan Aqueous LiV3O8/Zn Battery Using Zn/Li Hybrid Electrolyte.

Aqueous zinc-ion batteries (AZIBs) are promising candidates for large-scale energy storage because of their low cost and high safety. However, their practical applications are impeded by low energy density and short service life. Here, an aqueous Zn2+/Li+ hybrid-ion battery is fabricated using the LiV3O8 nanorods as the cathode, metallic Zn as the anode, and 3 M Zn(OTf)2 + 0.5 M LiOTf aqueous solution as the electrolyte. Compared with the batteries using pure 3 M Zn(OTf)2 electrolyte, the cycle performance of the hybrid-ion battery is significantly improved. After 4000 cycles at 5 A g1, the remaining capacity is 163.9 mA h g-1 with impressive capacity retention of 87.0%. Ex-situ XRD, ex-situ XPS, and SEM tests demonstrate that the hybrid electrolyte can inhibit the formation of the irreversible Zn3(OH)2V2O7·2H2O by-product and restrict Zn dendrite growth during cycling, thereby improving the cycle performance of the batteries.

A Clinical-Radiomics Nomogram Based on Computed Tomography for Predicting Risk of Local Recurrence After Radiotherapy in Nasopharyngeal Carcinoma.

Purpose: We aimed to establish a nomogram model based on computed tomography (CT) imaging radiomic signature and clinical factors to predict the risk of local recurrence in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods: This was a retrospective study consisting of 156 NPC patients treated with IMRT. Radiomics features were extracted from the gross tumor volume for nasopharynx (GTVnx) in pretreatment CT images for patients with or without local recurrence. Discriminative radiomics features were selected after t-test and the least absolute shrinkage and selection operator (LASSO) analysis. The most stable model was obtained to generate radiomics signature (Rad_Score) by using machine learning models including Logistic Regression, K-Nearest neighbor, Naive Bayes, Decision Tree, Stochastic Gradient Descent, Gradient Booting Tree and Linear Support Vector Classification. A nomogram for local recurrence was established based on Rad_Score and clinical factors. The predictive performance of nomogram was evaluated by discrimination ability and calibration ability. Decision Curve Analysis (DCA) was used to evaluate the clinical benefits of the multi-factor nomogram in predicting local recurrence after IMRT. Results: Local recurrence occurred in 42 patients. A total of 1,452 radiomics features were initially extracted and seven stable features finally selected after LASSO analysis were used for machine learning algorithm modeling to generate Rad_Score. The nomogram showed that the greater Rad_Score was associated with the higher risk of local recurrence. The concordance index, specificity and sensitivity in the training cohort were 0.931 (95%CI:0.8765-0.9856), 91.2 and 82.8%, respectively; whereas, in the validation cohort, they were 0.799 (95%CI: 0.6458-0.9515), 79.4, and 69.2%, respectively. Conclusion: The nomogram based on radiomics signature and clinical factors can predict the risk of local recurrence after IMRT in patients with NPC and provide evidence for early clinical intervention.