Obvious Weight Loss Research Articles

Tunable High-Performance Electromagnetic Interference Shielding of VO2 Nanowires-Based Composite.

The unique metal-insulator transition of VO2 is very suitable for dynamic electromagnetic (EM) regulation materials due to its sharp change in electrical conductivity. Here, we have developed an off/on switchable electromagnetic interference (EMI) shielding composite by interconnecting VO2 nanowires (NWs) in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to form conductive networks, resulting in outstanding performance at the X and Ku bands with maximum change values of 44.8 and 59.4 dB, respectively. The unique insulator-to-metal transition (IMT) of VO2 NWs has dominated the variation of polarization loss (εp″) and conductivity loss (εσ″) for the composites, which is the mechanism of EMI shielding switching between off and on states. Furthermore, the composite exhibits good cycling stability of the off/on switchable EMI shielding performance and has excellent mechanical properties, especially with 200 times abrasion resistance without obvious weight loss. This study provides a unique approach for dynamic switching of EM response with the potential to construct practical intelligent EM response systems for next-generation smart electromagnetic devices in various scenarios.

Abstract 3146: HRA00130-C004, a novel anti-DLL3 ADC with bystander effect, high DAR and favorable safety profiles

Abstract Small Cell Lung Cancer (SCLC) is a highly aggressive neuroendocrine tumor, accounting for ~15% of all new lung cancer cases1. It is estimated that there are 250,000 new SCLC cases and at least 200,000 deaths globally each year2. SCLC exhibits high recurrence after first-line treatment, poor response to subsequent therapies, and rare survival3. Lacking of recommended treatments for prolonging survival remains a problem over decades4. DLL3 is an inhibitory ligand of the Notch receptor. It binds to its Notch receptor through a cis-interaction, thus, mediates inhibition of Notch pathway to facilitate neuroendocrine tumorigenesis5. DLL3 is highly upregulated and aberrantly expressed on the cell surface in SCLC and other high-grade neuroendocrine tumors with limited expression in normal tissues6.Here we presented a DLL3-directed ADC, HRA00130-C004, which features a differentiated topoisomerase I inhibitor payload DXh conjugated via a cleavable linker to a humanized IgG1 antibody. HRA00130-C004 strongly inhibited the proliferation of cell lines with different DLL3 expression. In the bystander killing assays, HRA00130-C004 was able to kill both DMS53 cells (DLL3 over-expressed) and U-2OS (DLL3-negative) cells when they are co-cultured. The in vivo treatment of HRA00130-C004 resulted in a dramatic and sustained inhibition of tumor growth in H1184 (DLL3 high) and DMS53 (DLL3 low) xenograft models. No obvious weight loss was observed during the experiment. Furthermore, HRA00130-C004 demonstrated a favorable PK profile and satisfactory molecular integrity in rats with 3mg/kg dosing and cynomolgus monkeys with 10 mg/kg dosing. The exposure of total antibody and intact ADC was consistent. Moreover, HRA00130-C004 was well tolerated in rats and cynomolgus monkeys with no related adverse findings, which indicated its favorable safety profiles. In summary, taking advantage of Hengrui’s DXh platform, HRA00130-C004 has demonstrated great potency and good safety profiles. These data support the future clinical development of HRA00130-C004. 1.CA Cancer J. Clin., 2018, 68, 7; 2.J. Natl. Compr. Cancer Netw. 2018, 16, 1171; 3.Mol. Ther. Oncolytics, 2021, 20, 470; 4.Journal of Cancer, 2022, 13, 2945; 5.Cellular Oncology, 2019, 42, 261; 6.Journal of Hematology and Oncology 2019, 12, 61; Citation Format: Qingqing Yao, Changding Xue, Zhibin Xu, Lingfeng You, Zhendong Xue, Yuchang Mao, Sophie Lin, Jun Feng, Zhe Zhang, Xin Ye, Min Hu, Feng He. HRA00130-C004, a novel anti-DLL3 ADC with bystander effect, high DAR and favorable safety profiles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3146.

Pathogenic Characteristics of an Infection with Canine Influenza Virus and Streptococcus equi subsp. zooepidemicus Alone or in Combination in Mice

Both Streptococcus equi subsp. zooepidemicus (SEZ) and canine influenza virus (CIV) are two important pathogens causing infectious respiratory disease in dogs and are frequently codetected in respiratory secretions. However, the clinical significance of viral/bacterial coinfection remains unknown. This study investigated the pathogenic characteristics of infection with CIV and SEZ alone or in combination in mice. Our data indicated that the severity of the disease is related to the challenge order of CIV and SEZ. Coinfection of CIV and SEZ induced higher weight loss in mice than single infection, except for the VB group (viral followed by secondary bacterial infection). Compared with the concurrent or sequential infection groups of CIV and SEZ, mice in the CIV–SEZ preincubation group exhibited more obvious weight loss, higher mortality, and significantly enhanced burden of SEZ and CIV in tissues. Interestingly, viral and bacterial preincubation before coinfection caused typical pulmonary fibrosis in mice. Correspondingly, transforming growth factor (TGF)-β was upregulated, and its canonical small mother against decapentaplegic (Smad) 2/3 signaling was noticeably induced. Further investigation indicated that the activity of the viral neuraminidase (NA) enzyme upon sialic acid was considerably increased due to the direct interaction of CIV with SEZ, which may be related to the activation of the TGF-β signaling pathway. These findings implicate an unexpected contribution of the direct interaction between CIV and SEZ to synergistic pathogenicity.

Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein.

Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes lower respiratory diseases among infants and elderly people. Moreover, formalin-inactivated RSV (FI-RSV) vaccine induces serious enhanced respiratory disease (ERD). Radiation has been investigated as an alternative approach for producing inactivated or live-attenuated vaccines, which enhance the antigenicity and heterogeneous protective effects of vaccines compared with conventional formalin inactivation. In this study, we developed an RSV vaccine using gamma irradiation and analyzed its efficacy against RSV vaccine-induced ERD in a mouse model. Although gamma irradiation-inactivated RSV (RI-RSV) carbonylation was lower than FI-RSV carbonylation and RI-RSV showed a significant antibody production and viral clearance, RI-RSV caused more obvious body weight loss, pulmonary eosinophil infiltration, and pulmonary mucus secretion. Further, the conversion of prefusion F (pre-F) to postfusion F (post-F) was significant for both RI-RSV and FI-RSV, while that of RI-RSV was significantly higher than that of FI-RSV. We found that the conversion from pre- to post-F during radiation was caused by radiation-induced reactive oxygen species. Although we could not propose an effective RSV vaccine manufacturing method, we found that ERD was induced by RSV vaccine by various biochemical effects that affect antigen modification during RSV vaccine manufacturing, rather than simply by the combination of formalin and alum. Therefore, these biochemical actions should be considered in future developments of RSV vaccine. IMPORTANCE Radiation inactivation for viral vaccine production has been known to elicit a better immune response than other inactivation methods due to less surface protein damage. However, we found in this study that radiation-inactivated RSV (RI-RSV) vaccine induced a level of immune response similar to that induced by formalin-inactivated RSV (FI-RSV). Although RI-RSV vaccine showed less carbonylation than FI-RSV, it induced more conformational changes from pre-F to post-F due to the gamma radiation-induced reactive oxygen species response, which may be a key factor in RI-RSV-induced ERD. Therefore, ERD induced by RSV vaccine may be due to pre-F to post-F denaturation by random protein modifications caused by external stress. Our findings provide new ideas for inactivated vaccines for RSV and other viruses and confirm the importance of pre-F in RSV vaccines.

Preparation, Characterization, Release and Antibacterial Properties of Cinnamon Essential Oil Microcapsules

In this study, the antibacterial microcapsules of cinnamon essential oil (CEO) were prepared by complex condensation method. Chitosan quaternary ammonium salt (HACC) combined with gum arabic (GA) was selected as the coated wall material. The optimal preparation conditions of CEO microcapsules (CMSs) were determined by response surface methodology (RSM): the core/wall mass ratio was 1:1, the pH value was 4.5, the mass concentration of CaCl2 was 0.7 wt% and the actual encapsulation rate of microcapsules was 90.72% ± 1.89%. The morphology, size, composition and thermal stability of the prepared CMSs were characterized by scanning electron microscopy (SEM), laser particle size analysis (LPDA), Fourier transform infrared spectroscopy (FTIR), thermogravimetric differential thermal analysis (TG–DTA) and differential scanning calorimetry (DSC). In addition, the in vitro drug release and antibacterial properties of CMS were also evaluated. The results showed that CMS was spherical, with an average particle size of 6.31 µm. The obvious weight loss occurred at 269 °C and the corresponding DSC curve had an obvious exothermic peak at 265.5 °C, which had an increase compared with CEO. Microcapsules can achieve slow release, with the lowest and highest release rates being 19.66% and 49.79%, within 30 days. The drug release curve of essential oil of microcapsules was consistent with a first-order release model named ExpDec1. Based on the above research results, the CMS can effectively improve the stability of essential oil, achieve slow release and prolong the antibacterial effect, indicating its potential applications in food, cosmetics and medicine.

Effects and mechanism of L-Carnitine on weight loss

L-Carnitine, as an essential coenzyme in fat metabolism, can promote the metabolism of human fat, accelerate the burning of fat, and may achieve the desired fat burning slimming effect; This papers studies the effect of L-carnitine on weight loss and the possible side effects it may bring to the human body, explains the weight loss principle and metabolic pathway of L-carnitine from the molecular level, and discusses the relationship between exercise and L-carnitine in combination with metabolism, give the author recommendations for using L-Carnitine. A brief explanation of the current state of development of L-carnitine diet pills (supplements) in the field of health was described. Combined with the comparison and summary of existing databases, it is concluded that L-carnitine alone is not an ideal choice, and L-carnitine alone is used without exercise: For people with normal weight, L-carnitine has no effect on weight loss. Obviously, only overweight, and obese people, taking L-carnitine combined with a lot of training have obvious weight loss effect.

Ecological and dynamic analysis of gut microbiota in the early stage of azomethane-dextran sodium sulfate model in mice.

The success rate of azomethane-dextran sodium sulfate (AOM-DSS) model in mice has been a long-standing problem. Treatment of AOM and the first round DSS induces acute colitis and is of great significance for the success of AOM-DSS model. In this study, we focused on the role of gut microbiota in the early stage of AOM-DSS model. Few mice with obvious weight loss and high disease-activity score survived from double strike of AOM and the first round DSS. Different ecological dynamics of gut microbiota were observed in AOM-DSS treated mice. Pseudescherichia, Turicibacter, and Clostridium_XVIII were of significance in the model, uncontrolled proliferation of which accompanied with rapid deterioration and death of mice. Akkermansia and Ruthenibacterium were significantly enriched in the alive AOM-DSS treated mice. Decrease of Ligilactobacillus, Lactobacillus, and Limosilactobacillus were observed in AOM-DSS model, but significant drop of these genera could be lethal. Millionella was the only hub genus of gut microbiota network in dead mice, which indicated dysbiosis of the intestinal flora and fragility of microbial network. Our results will provide a better understanding for the role of gut microbiota in the early stage of AOM-DSS model and help improve the success rate of model construction.

A Case Report of Brain Metastases after Neoadjuvant Chemo and Radiotherapy for Esophagogastric Junction Adenocarcinoma in an Adult Male Patient

Background: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy. The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain.
 Case Presentation: A male patient, 47 years old, was admitted to the hospital on July 31, 2020, mainly due to "progressive dysphagia. Two months ago, the patient had difficulty eating without obvious incentives, especially when eating hard food such as rice. The liquid diet was acceptable, accompanied by retrosternal pain and discomfort, heartburn, and obvious weight loss. The symptoms gradually aggravated without obvious relief.
 Conclusion: In summary, there are few international investigations and an absence of relevant information and literature on the environment in which tumor cells survive after radiotherapy. Clinicians can't ignore the issue of whether radiotherapy will alter the tumor cells' natural environment, leading to tumor cell escape and an increase in brain metastases.

Gas corrosion behavior of calcium hexaluminate materials for hydrogen metallurgy

Calcium hexaluminate (CA6) has good chemical stability under H2 atmosphere, which indicates its application prospect in the hydrogen metallurgy field. However, iron ores usually contain SiO2 impurities, which can react with H2 to form Si-containing gases such as SiO (g) and SiO2 (g). The Si-containing gases might corrode CA6-based lining refractories during hydrogen metallurgy. The silica and magnetite were heated in a hydrogen furnace to simulate the gaseous environment of hydrogen metallurgy in this paper. At the same time, the corrosion of CA6 materials at elevated temperature (600 °C–1800 °C) under the hydrogen metallurgy atmosphere were studied. In addition, three SiO2 based raw materials (silica, fused silica and waste silica brick) with different SiO2 contents were used to investigate the effect of impurities on the their H2 corrosion. The result showed that SiO2 based raw materials had good chemical stability under H2 atmosphere at the temperature lower than 1200 °C, obvious weight loss appeared at 1400 °C, the impurities including Fe2O3 and MgO would accelerate mass loss under H2 atmosphere. Gases including SiO (g), SiO2 (g) and H2O (g) could react with CA6 to form corundum and yoshiokaite at 1800 °C, which resulted in 3.16% weight gain after heating at 1800 °C for 8 h under the hydrogen metallurgy atmosphere. No significant mass change and mineral phase transformation appeared at the reaction temperature less than 1600 °C.

Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model.

Antibody drug conjugates (ADC) are one of the attractive modalities for the treatment of acute myeloid leukemia (AML). Previously, we have developed ASP1235, a novel ADC targeting Fms-like tyrosine kinase 3 (FLT3) which is widely expressed on the leukemic blasts of AML patients. In this study, we sought to evaluate the therapeutic effect of ASP1235 in combination with venetoclax plus azacitidine, a novel standard-of-care treatment for elderly AML patients, in ASP1235 poor sensitive AML cells. To identify the suitable preclinical model, we first evaluated the growth inhibitory effect of ASP1235 on several leukemia cell lines expressing FLT3 and found that THP-1 cells were partially sensitive to ASP1235 in vitro. Furthermore, ASP1235 showed marginal anti-tumor activity in a THP-1 xenograft model. Compared to the leukemic blasts in most of the relapsed or refractory (R/R) AML patients tested, THP-1 cells expressed equivalent protein levels of Bcl-2, suggesting that ASP1235 in combination with venetoclax plus azacitidine is a rational treatment in the THP-1 model. In vitro, ASP1235 showed a cytotoxic effect on THP-1 cells in combination with venetoclax, and the combination effect was greater than the additive effect. Furthermore, ASP1235 also showed a combination effect with venetoclax plus azacitidine treatment. Similarly, the combination of ASP1235, venetoclax and azacitidine showed a superior anti-tumor effect in a THP-1 xenograft model without obvious body weight loss. These findings provide supportive evidence that the triple combination of ASP1235, venetoclax and azacitidine would improve the clinical outcome of ASP1235 monotherapy and venetoclax plus azacitidine regimen in AML patients.

Aumolertinib inhibits growth of human choroidal melanoma MUM-2B cells in vitro and in vivo

To investigate the inhibitory effect of aumolertinib on proliferation of human choroidal melanoma MUM-2B cells and explore the possible molecular mechanism. CCK-8 assay and colony formation assay were used to evaluate the inhibitory effect of different concentrations of aumolertinib on viability and proliferation of MUM-2B cells. Flow cytometry was performed to analyze the apoptosis, necrosis, cellular ROS production and cell cycle changes in aumolertinib- treated MUM-2B cells. The antitumor effect of aumolertinib against human choroidal melanoma was observed in nude mouse models bearing MUM-2B tumor cell xenografts. The results of CCK-8 and colony formation assay showed that aumolertinib strongly inhibited the proliferation MUM-2B cells in a dose-dependent manner. Flow cytometry showed that aumolertinib dose-dependently increased the total apoptosis rate of MUM-2B cells to as high as 76.65% at the concentration of 8 μmol/L and induced obvious cell cycle arrest at G1 phase. Aumolertinib treatment also caused a dose-dependent increase of ROS production and reduction of mitochondrial membrane potential in MUM-2B cells. In the tumor-bearing nude mice, treatment with aumolertinib significantly inhibited tumor growth without causing obvious body weight loss. Aumolertinib can effectively inhibit the growth of human choroidal melanoma MUM-2B cells both in vivo and in vitro, suggesting its potential clinical value in the therapy of choroidal melanomas.

Allyl compound with fully biomass content derived from 2,5-furandicarboxylic acid and eugenol to form high-performance thiol-ene click polymers

Designing and preparing a biomass-based monomer with fully biomass content is of great significance for achieving sustainability, which is in line with the target of Carbon neutrality and Carbon peak. In this work, an allyl compound (FDEU) was designed and synthesized derived from eugenol (Eu) and 2,5-furandicarboxylic acid (FDCA), and the biomass content of FDEU was as high as 100%. Two thiol-ene crosslinked polymers (TCPs), FDEU/4SH and FDEU/3SH, were prepared via solvent-free UV-light thiol-ene click reaction. The curing behavior and combination properties which include thermal properties, thermal mechanical properties, mechanical properties, and thermal stability of FDEU/4SH and FDEU/3SH were systematically investigated. The results showed that FDEU/4SH and FDEU/3SH had similar curing reactivity, and FDEU/4SH exhibited better thermal resistance, modulus, and strength. In particular, the glass transition temperature (TgDMA) of FDEU/4SH was 66.6 °C. Additionally, the tensile strength of FDEU/4SH was (56.2 ± 2.3) MPa; and tensile modulus of FDEU/4SH was (1.4 ± 0.2) GPa. Moreover, FDEU/4SH exhibited excellent thermal stability without obvious weight loss (Td5%) of 311.5 °C. The factor behind these excellent comprehensive properties of FDEU/4SH is its well-designed chemical structure of FDEU, which not only has 100% of biomass content but also has a rigid aromatic structure and furan ring.

Investigation on Application Prospect of Refractories for Hydrogen Metallurgy: The Enlightenment from the Reaction between Commercial Brown Corundum and Hydrogen.

Hydrogenous environments put forward new requirements to refractories for the hydrogen metallurgy field. The temperature and impurities in refractories played an important role in stability. A commercial brown corundum with many impurities was adopted as a raw material, thermodynamic calculations and reduction experiments of the brown corundum by high-purity hydrogen (99.99%) were accepted to investigate the stability of the oxides. The weight loss and mass fraction were tested to estimate the stability of the oxides in the brown corundum. XRD and SEM were used to analyze the mineral compositions and microstructures. The results showed that: the thermodynamic stability of the oxides in the brown corundum under high-purity hydrogen was in the order of Al2O3 > CaO > MgO > SiO2 > TiO2 > Fe2O3 at temperatures lower than 1400 °C. Obvious weight loss appeared after heating at 1400 °C for 8 h. The content of CaO did not decline after reduction even at 1800 °C, owing to the formation of hibonite (CaAl12O19), high-purity Al2O3 and CaAl12O19 -based refractories had the prospect for lining materials in the hydrogen metallurgy field, owing to their excellent chemical stability under hydrogenous environments.

Murine diabetic models for dengue virus infection.

Dengue virus (DENV) is a critical public health concern in tropical and subtropical regions worldwide. Thus, immunocompetent murine models of DENV infection with robust viremia are required for vaccine studies. Diabetes is highly prevalent worldwide, making it frequent comorbidity in patients with dengue fever. Therefore, murine models are needed to understand viral pathogenesis and disease progression. Acquired-induced and inherently diabetic C57BL/6 and db/db mice were inoculated with DENV-3 via the tail vein. After infection, both the diabetic C57BL/6 and db/db mice showed obvious weight loss with clinical manifestations. Quantitative reverse-transcription polymerase chain reactionrevealed robust and replicable viremia in the two types of diabetic mice. Immunohistochemical detection showed persistent DENV-3 infection in the liver. Enzyme-linked immunosorbent assay for cytokine detection revealed that diabetic mice showed more severe inflammatory responses than did nondiabetic mice, and significant histological alterations were observed in diabetic mice. Thus, the diabetic mice were more susceptible to DENV infection than the nondiabetic mice. Taken together, we established two types of immunocompetent diabetic mice for DENV infection, which can be used to further study the mechanisms of dengue pathogenesis in diabetes and to develop antiviral pharmaceuticals and treatments.

Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation

A series of novel N-alkyl-N-hydroxyl carboximates derived from β-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound β-elemene (1). Notably, compound 11i exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound 11i could significantly induce cell apoptosis. Further in vivo study in the H460 xenograft mouse model validated the anti-tumour activities of 11i with a greater tumour growth inhibition (TGI, 68.3%) than β-elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such N-alkyl-N-hydroxyl carboximate class of compounds exemplified as 11i demonstrated potent anticancer activities both in vitro and in vivo, and should warrant further investigation for potential anticancer therapy.

E.faecium QH06 alleviates TNBS-induced colonic mucosal injury in rats

To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity. Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed. The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae. E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.

Ash composition, structural characteristics and thermal conversion performance of Texaco gasifier based on Zhundong coal

Composition and structure characteristics of fine slag (FS) and coarse slag (CS) discharged from Texaco gasifier with Zhundong coal as raw material were analyzed, and their thermochemical conversion properties were analyzed. Proximate and ultimate analyses show that the contents of fixed carbon in coarse slag are 42.31%, indicating that it can be used as raw material to realize its high-added utilization. Analysis with Fourier transform infare spectrometer (FT-IR) suggest that the absorption peak of Si-O in coarse slag and fine slag is stronger, and there is a small amount of aromatic structure in fine slag. Thermal decomposition behaviors in inert atmosphere show that the maximum weight loss rate peak of coarse slag is located around 600 °C, while that of fine slag is transferred to about 620 °C. Results of thermal decomposition in oxidization atmosphere show that there are obvious weight loss rate peaks derived from combustion of the fixed carbon in 500–700 °C. The weight loss profiles of fine slag and coarse slag in inert and oxidization atmosphere were fitted by Coats-Redfern method. The kinetic parameters including pyrolysis/combustion activation energy and correlation coefficient were calculated. The results show that the fitting effect is better as the reaction order selected as 3 at the intense pyrolysis section (560–640 °C) for coarse slag in inert atmosphere, with correlation coefficient R2 of 0.99 and activation energy E of 38.85 kJ/mol. Similarly, in the intense pyrolysis stage (590–650 °C) of fine slag, the fitting effect is better as the reaction order selected 3, with the correlation coefficient R2 of 0.97 and the activation energy E of 79.09 kJ/mol. In oxidization atmosphere, at the intense combustion stage of coarse slag (540–605 °C) and fine slag (530–605 °C), the fitting effect is better as n=1 for the both slags, with the activation energy E of 226.46 and 154.73 kJ/mol respectively.

Interventions for Body Composition and Upper and Lower Extremity Muscle Strength in Older Adults in Rural Taiwan: A Horizontal Case Study.

The purpose of this study was to understand the effects of a physical activity program and high-protein supplementation on body composition and upper and lower extremity muscle strength in male older adults in rural areas. In this study, 60 healthy male older adults (mean age 77.5 ± 4.6 years) from rural areas were recruited and randomly assigned to experimental group A (intervention of the physical activity program and high-protein supplementation), experimental group B (daily routine, with only intervention of high-protein supplementation), or control group C (daily routine). Experimental group A (EGa) carried out a physical activity plan three times a week, with an exercise intensity and calorie consumption of 250 kcal (5METs × ⅔hr × 75) for 3 months and drank a high-protein supplement (1.3 g/kg BW/day) after each exercise; experimental group B (EGb) followed only the intervention of high-protein supplementation. All the participants underwent pre- and post-tests for body composition, waist–hip circumference (WC, HC), handgrip strength (HS), 30 s dominant arm curl, 30 s sit to stand, and 2 min step tests. The results of the study showed that EGa significantly decreased body mass index (BMI), body fat mass (BFM), body fat percentage (BFP), WC, HC, and waist-to-hip ratio (WHR) and increased basal metabolic rate and muscle mass. Although both EGa and EGb used high-protein supplementation, EGa’s added three-month intervention of a physical activity program made it easier for that group to increase muscle mass and muscle strength. The WHR decreased from 1.015 to 0.931, representing a decrease of 8.28%, and an obvious weight loss effect was achieved. Thus, we concluded that the best way to maintain muscle strength in older adults is through physical activity with resistance and protein supplementation, which can reduce muscle loss in older adults.

Comparison of distal pancreatectomy with celiac axis resection and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ2 test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ2=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ2=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.

Design, Synthesis and Structure-Activity Relationship Studies of Meridianin Derivatives as Novel JAK/STAT3 Signaling Inhibitors.

Hyperactivation of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling is an attractive therapeutic target for tumor therapy. Herein, forty-eight novel meridianin derivatives were designed and synthesized, and their antitumor activity was evaluated in vitro both for activity optimization and structure–activity relationship (SAR) study. The results indicated that most derivatives exhibited significantly improved antitumor activity, especially for compound 6e. The compound 6e contains an isothiouronium linked by an alkyl chain consisting of six carbon atoms with IC50 ranging from 1.11 to 2.80 μM on various cancer cell lines. Consistently, the 6e dose dependently induced the apoptosis of A549 and DU145 cells, in which STAT3 is constitutively active. Western blotting assays indicated that the phosphorylation levels of JAK1, JAK2 and STAT3 were inhibited by 6e at 5 μM without significant change in the total STAT3 level. Moreover, 6e also suppressed the expression of STAT3 downstream genes, including c-Myc, Cyclin D1 and Bcl-XL at 10 μM. An additional in vivo study revealed that 6e at the dose of 10 mg/kg could potently inhibit the DU145 xenograft tumor without obvious body weight loss. These results clearly indicate that 6e could be a potential antitumor agent by targeting the JAK/STAT3 signaling pathway.