A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes: The EARLY Randomized Clinical Trial.

Importance: An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide additional benefits to patients with type 2 diabetes. Objective: To evaluate the effect of the 5:2 MR on glycemic control among patients with early type 2 diabetes compared with metformin and empagliflozin. Design, Setting, and Participants: The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized, open-label, active parallel-controlled clinical trial conducted between November 13, 2020, and December 29, 2022, in 9 centers across China. A total of 509 eligible patients underwent screening, out of which 405 were randomly assigned to 3 groups and included in the intention-to-treat analysis. Interventions: Patients were randomly allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or 5:2 MR. The treatment was 16 weeks, with an 8-week follow-up. Main Outcomes and Measures: The primary end point was the change in hemoglobin A1c (HbA1c) level from baseline to 16 weeks. Secondary end points included changes in body weight, anthropometric measurements, and biochemical parameters. Results: Of the 405 randomized participants (265 men [65.4%]; mean [SD] age, 45.5 [11.0] years; mean [SD] body mass index, 29.5 [4.1]; and mean [SD] HbA1c level, 7.9% [0.6%]), 332 completed the 16-week treatment. From baseline to week 16, participants in the 5:2 MR group showed the greatest reduction in HbA1c (least-squares mean [LSM], -1.9% [SE, 0.2%]), significantly greater than patients receiving metformin (LSM, -1.6% [SE, 0.2%]; adjusted LSM difference, -0.3% [95% CI, -0.4% to -0.1%]) and empagliflozin (LSM, -1.5% [SE, 0.2%]; adjusted LSM difference, -0.4% [95% CI, -0.6% to -0.2%]). At week 16, the mean weight loss in the 5:2 MR group (LSM, -9.7 kg [SE, 2.2 kg]) was greater than that in the metformin group (LSM, -5.5 kg [SE, 2.3 kg]) and empagliflozin group (LSM, -5.8 kg [SE, 2.3 kg]). Conclusions and Relevance: This randomized clinical trial of Chinese adults with overweight or obesity and with early type 2 diabetes found that 5:2 MR could improve glycemic outcomes and weight loss in the short term compared with metformin or empagliflozin, making it a promising initial intervention and early management for type 2 diabetes. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040656.

Sacrificial scaffold-assisted direct ink writing of engineered aortic valve prostheses.

Heart valve disease has become a serious global health problem, which calls for numerous implantable prosthetic valves to fulfill the broader needs of patients. Although current three-dimensional (3D) bioprinting approaches can be used to manufacture customized valve prostheses, they still have some complications, such as limited biocompatibility, constrained structural complexity, and difficulty to make heterogeneous constructs, to name a few. To overcome these challenges, a sacrificial scaffold-assisted direct ink writing approach has been explored and proposed in this work, in which a sacrificial scaffold is printed to temporarily support sinus wall and overhanging leaflets of an aortic valve prosthesis that can be removed easily and mildly without causing any potential damages to the valve prosthesis. The bioinks, composed of alginate, gelatin, and nanoclay, used to print heterogenous valve prostheses have been designed in terms of rheological/mechanical properties and filament formability. The sacrificial ink made from Pluronic F127 has been developed by evaluating rheological behavior and gel temperature. After investigating the effects of operating conditions, complex 3D structures and homogenous/heterogenous aortic valve prostheses have been successfully printed. Lastly, numerical simulation and cycling experiments have been performed to validate the function of the printed valve prostheses as one-way valves.

Experimental investigation on high-pressure methane jet characteristic single-hole injector.

High-pressure gas direct injection (DI) technology benefits engines with high efficiency and clean emissions, and the gas jet process causes crucial effects especially inside an mm-size space. This study presents an investigation on the high-pressure methane jet characteristics from a single-hole injector by analysing jet performance parameters including jet impact force, gas jet impulse, and jet mass flow rate. The results show that the methane jet exhibited a two-zone behaviour along the jet direction in the spatial dimension induced by high-speed jet flow from the nozzle: zone 1 near the nozzle-the jet impact force and jet impulse increased consistently except for a fluctuation due to shock wave effects induced by the sonic jet and no entrainment occurs, and zone II farther away from the nozzle-the jet impact force and jet impulse became stable when the shock wave effects became weak and the jet impulse was conserved with a linear conservation boundary. The Mach disk height was exactly the turning point of two zones. Moreover, the methane jet parameters, such as the methane jet mass flow rate, jet initial jet impact force, jet impulse, and Reynolds number had a monotonous and linearly increasing correlation with injection pressure.

Experimental Study of Dual-Fuel Diesel/Natural Gas High-Pressure Injection.

Dual-fuel diesel/natural gas direct-injection engine is promising and highly attractive due to its low-carbon emission and high thermal efficiency, and both high-pressure diesel and natural gas injections are critical for air-fuel mixing. This study presents an optical experimental investigation on the high-pressure dual-fuel diesel/methane injection process based on a constant-volume vessel test rig. The results show that the diesel penetration process of the dual-fuel injection experiences two stages: Stage I, the diesel tip penetration S diesel, the diesel spray area A diesel, and the diesel spray perimeter C diesel of the dual-fuel injection are smaller than those of the single diesel injection. Stage II, both the diesel and methane continue to penetrate forward, and S diesel, A diesel, and C diesel of the dual-fuel injection become larger than those of the single diesel injection do. The diesel injection pressure causes effect on the dual-fuel spray penetration. The diesel injection pressure directly causes linear influence on the two-stage dual-fuel injection characteristic. As the diesel injection pressure increases, the diesel spray meets the methane jet advancer and the cross point occurs linearly earlier. Furthermore, the dual-fuel injection is asymmetric and the methane gas jet enhances this asymmetry so that the spray cone shifts to the side of the methane gas jet.

Astragaloside attenuates lipopolysaccharide-induced cell apoptosis in human gingiva cells via MAPK signaling pathway.

SUBJECTS: The aim of this study was to research the antiapoptotic effect of astragaloside, the principal component of Astragalus membranaceus (Fisch) Bge, in human gingiva cells induced by lipopolysaccharide (LPS). METHODS: According to the treatment, human gingiva cells were divided into five groups, including (1) control group without drug treatment; (2) imitating group, treated with LPS (10 µg·mL-1 ) alone; (3) low group, treated with LPS and 50 µmol·L -1 astragaloside; (4) medium group, treated with LPS and 100 µmol·L -1 astragaloside; and (5) high group, treated with LPS and 150 µmol·L -1 astragaloside. Cell proliferation and apoptosis were investigated using MTT assay and flow cytometry, respectively. Apoptosis and mitogen-activated protein kinase associated proteins were determined using Western blot analysis. RESULTS: LPS significantly suppressed the proliferation of human gingiva cells, but astragaloside obviously attenuated this change with a dose-dependent manner. LPS significantly promoted the apoptosis of human gingiva cells, but astragaloside treatments significantly attenuated this change with a dose-dependent manner. In addition, LPS could significant upregulated the expression of P-p38, P-JNK, Bax, and caspase-3. CONCLUSION: Astragaloside preformed a promising antiapoptotic role in apoptosis of human gingiva cells induced by LPS. This finding might provide us with a novel therapeutic method in tooth protection.

Synthesis of Sulfonylated Lactams by Copper-Mediated Aminosulfonylation of 2-Vinylbenzamides with Sodium Sulfinates.

Treatment of 2-vinylbenzamide derivatives with sulfinate sodium in the presence of Cu(NO3)2·3H2O led to an intra/intermolecular aminosulfonylation reaction to produce sulfonylated lactams in moderate to good yields. The developed method features the easily available and stable sulfone reagents, ease of operation, and a broad functional group tolerance.

Self-propagating Combustion Triggered Synthesis of 3D Lamellar Graphene/BaFe12O19 Composite and Its Electromagnetic Wave Absorption Properties.

The synthesis of 3D lamellar graphene/BaFe12O19 composites was performed by oxidizing graphite and sequentially self-propagating combustion triggered process. The 3D lamellar graphene structures were formed due to the synergistic effect of the tremendous heat induced gasification as well as huge volume expansion. The 3D lamellar graphene/BaFe12O19 composites bearing 30 wt % graphene present the reflection loss peak at -27.23 dB as well as the frequency bandwidth at 2.28 GHz (< -10 dB). The 3D lamellar graphene structures could consume the incident waves through multiple Reflection and scattering within the layered structures, Prolonging the propagation path of electromagnetic waves in the absorbers.

Expanded graphite embedded with aluminum nanoparticles as superior thermal conductivity anodes for high-performance lithium-ion batteries.

The development of high capacity and long-life lithium-ion batteries is a long-term pursuing and under a close scrutiny. Most of the researches have been focused on exploring electrode materials and structures with high store capability of lithium ions and at the same time with a good electrical conductivity. Thermal conductivity of an electrode material will also have significant impacts on boosting battery capacity and prolonging battery lifetime, which is, however, underestimated. Here, we present the development of an expanded graphite embedded with Al metal nanoparticles (EG-MNPs-Al) synthesized by an oxidation-expansion process. The synthesized EG-MNPs-Al material exhibited a typical hierarchical structure with embedded Al metal nanoparticles into the interspaces of expanded graphite. The parallel thermal conductivity was up to 11.6 W·m-1·K-1 with a bulk density of 453 kg·m-3 at room temperature, a 150% improvement compared to expanded graphite (4.6 W·m-1·K-1) owing to the existence of Al metal nanoparticles. The first reversible capacity of EG-MNPs-Al as anode material for lithium ion battery was 480 mAh·g-1 at a current density of 100 mA·g-1, and retained 84% capacity after 300 cycles. The improved cycling stability and system security of lithium ion batteries is attributed to the excellent thermal conductivity of the EG-MNPs-Al anodes.

[Clinical application of surgical intervention model for repairing tuberculosis wound with sinus tract].

OBJECTIVE: To retrospectively explore the effectiveness of surgical intervention model for repairing the tuberculosis wound with sinus tract. METHODS: Forty-three patients with tuberculosis wound with sinus tract who met the inclusion criteria were admitted to the 309th Hospital of PLA from January 2010 to October 2015. These patients were divided into test group (n=38) and control group (n=5) according to the different treatment and patient's consent. Patients in test group were treated as follows. Firstly, antituberculosis drugs were taken orally for at least 3 weeks, and the wounds were accurately assessed using magnetic resonance imaging combined with 3-dimensional reconstruction software. Then sinus tract and its surrounding devitalized tissue were completely excised, and vacuum sealing drainage (VSD) treatment with negative pressure value of -26.6 kPa was performed for 1 to 2 weeks (dressing change was performed per 7 days). Lastly, the wounds were covered through direct suture or grafting skin or flap. Patients in control group were firstly given antituberculosis drugs orally for at least 3 weeks, and then they were treated with routine dressing change in outpatient service every 3 days. After the former therapy, patients in both groups were given antituberculosis drugs by oral administration for at least 6 months and were followed up for 6 to 36 months. Detection of Bacillus tuberculosis, Acid-fast bacilli, and tuberculosis granuloma, wound healing time, and relapse of tuberculosis wound in patients of both groups were recorded. The rates of single sinus tract, two sinus tracts, and more than or equal to 3 sinus tracts of patients in test group were recorded. Data were processed with Fisher's exact test and Wilcoxon rank-sum test. RESULTS: Bacillus tuberculosis was respectively detected in wounds of 5 patients in test group and 2 patients in control group. Acid-fast bacilli were positively expressed in wounds of 8 patients in test group and 3 patients in control group. A typical tuberculosis granuloma phenomenon was observed in the wounds of 27 patients in test group and 4 patients in control group. These differences in above-mentioned 3 indexes between two groups were not statistically significant (with P values respectively 0.238 4, 0.154 4, 1.000 0). The median of wound healing time of patients in test group was 19.6 d, which was significantly shorter than that in control group (94.4 d, χ(2)=12.986 0, P=0.000 3). There were 2 and 1 patients with recurrent tuberculosis wound in test group and control group respectively, without statistically significant difference (P=0.363 0). Among patients in test group, the rate of single sinus tract was 23.7%(9/38), the rate of two sinus tracts was 28.9%(11/38), and the rate of more than or equal to 3 sinus tracts was 47.4% (18/38). CONCLUSIONS: Repairing the tuberculosis wound with sinus tract in surgical intervention model of antituberculosis therapy+ accurate wound assessment+ debridement+ VSD treatment+ surgical repair is beneficial to making the optimal operation plan under the premise of knowing location of sinus tract, which can reduce surgical risk.

Split Ssp DnaB mini-intein-mediated production of recombinant human glucagon-like peptide-1/7-36.

Glucagon-like peptide-1 (GLP-1) plays an important role in the regulation of postprandial insulin release. Here, we used the split DnaB mini-intein system to produce recombinant human GLP-1/7-36 (rhGLP-1) in Escherichia coli. The C-terminal domain of DnaB mini-intein (IntC) was genetically fused at the N-terminus of rhGLP-1 to produce IntC-GLP-1. IntC-GLP-1 and N-terminal domain of DnaB mini-intein (IntN) protein were prepared in a denatured buffer of pH 8.0. IntC-GLP-1 was diluted 1:8 into the phosphate buffer of pH 6.6. IntN was added into the diluted solution of IntC-GLP-1 at the molar ratio of 1:2. Then, rhGLP-1 was released from IntC-GLP-1 via inducible C-terminal peptide-bond cleavage by shifting pH from 8.0 to 6.6 at 25 °C for 24-H incubation. Then, the supernatant was applied to a Ni-Sepharose column, and the pass through fraction was collected. About 5.34 mg of rhGLP-1 with the purity of 97% was obtained from 1 L of culture medium. Mass spectrometry showed the molecular weight of 3,300.45 Da, which was equal to the theoretical value of GLP-1/7-36. The glucose-lowering activity of rhGLP-1 was confirmed by the glucose tolerance test in mice. In conclusion, the reported method was an efficient strategy to produce rhGLP-1 without using enzyme or chemical reagents, which could also be used for other similar peptides.

Assessment of serum arginase I as a type 2 diabetes mellitus diagnosis biomarker in patients.

Previous studies have reported that levels of serum arginase I are increased in certain diseases. However, the exact association between arginase I and diabetes mellitus (DM) has yet to be determined. The aim of the present study was to investigate the correlation between arginase I activity and DM to determine whether arginase I activity may be used as a diagnostic biomarker for DM. DM was induced by a streptozotocin injection, while the arginase inhibitor, citrulline, was administered daily. Serum levels of glucose, reactive oxygen species (ROS) and arginase I activity were analyzed, and quantitative polymerase chain reaction and western blot analysis were performed to detect the mRNA and protein expression levels of arginase I, respectively. In addition, western blot analysis was used to determine the protein expression of the Tie 2 receptor. Pearson's analysis was used to determine the correlation between arginase I activity and Tie 2 expression, while concordance analysis was performed using the Cohen's test to obtain the Kappa statistic. The results demonstrated that serum arginase I activity levels in the rats with DM were significantly elevated compared with the control group, and positively correlated with the blood glucose levels. In addition, the blood glucose and ROS levels were increased significantly in the rats with DM. Arginase I mRNA and protein expression levels were significantly elevated in the diabetic rats when compared with the control group, and Tie 2 expression levels increased and were shown to correlate with arginase I activity in the diabetic rats. In addition, arginase I activity was shown to correlate with glucose intolerance and post-load glucose values. Good concordance was observed between arginase I activity and the clinical diagnosis for DM (κ=0.876; P<0.001). Therefore, the results indicated that arginase I may function as a diagnostic biomarker for DM rats model.

Construction and characterization of a novel chimeric antibody c3C7 specific for the integrin αIIbß3 complex.

A murine monoclonal antibody (mAb) 3C7 against integrin αIIbß3 was previously obtained as a potential antithrombotic agent in our laboratory. The epitope of 3C7 is a specific conformation of the αIIbß3 complex, but not either of the two subunits, which makes it different from abciximab, a supplementary antibody drug used in percutaneous coronary intervention which has a cross-reaction with other integrins sharing the ß3 subunit. To reduce the human anti-mouse antibody reactions of 3C7, the variable regions of this antibody were cloned and fused with the constant counterparts of human IgG1. Two vectors of light and heavy chains were constructed and co-transfected into CHO-dhfr(-) cells. The chimeric antibody c3C7 was purified and the properties of c3C7 were compared with 3C7. Identical to its parent antibody 3C7, c3C7 binds to the αIIbß3 complex, but not to either of the subunits. The K(d) value of c3C7 was in the same order of magnitude as 3C7 (1.570 ± 0.326 vs 0.780 ± 0.182 nmol/L). Human platelet aggregation induced by adenosine diphosphate was effectively inhibited by c3C7 in a dose-dependent manner. In conclusion, after the modification, c3C7 retained the properties of its parent mAb with no loss of its biological activity. Therefore, c3C7 has the potential to become a novel agent for the treatment of thrombosis.

Pleuropneumonectomy for diffuse pleural metastasis in primary lung cancer.

OBJECTIVE: The purpose of this study is to analyze a single institution experience with pleuropneumonectomy for pleural metastasis and malignant pleural effusion in primary lung cancer. MATERIALS AND METHODS: From August 1978 to August 2011, 66 consecutive patients with lung cancer underwent pleuropneumonectomy. Patients were followed-up after the operation. The quality-of-life and the survival time were recorded. RESULTS: All the 66 patients were successfully operated on, including 38 patients in early years (1978-1993) and 28 patients in recent years (1994-2011). Two patients in early years died after the operation. Post-operative complications occurred including heart arrhythmia, respiratory insufficiency and bacterial infection of residual lung, chylothoraxin and mental disorder. A total of 61 patients have been successfully followed-up and three patients in early years were lost in 1 year after the operation. Local recurrence was found in seven cases (4 in early years, 3 in recent years) and distant metastasis was found in 48 cases (29 in early years, 19 in recent years). A total of 54 patients died from tumors, seven patients survived. The actuarial 1, 2 and 3-year survival rates are 72.7%, 27.2% and 6.1% of 36 in patients of early years and 85.7%, 46.4% and 21.4% in 28 patients of recent years. The mean survival and the median survival of the total 64 patients were 20.0 ± 10.9 months and 17 months respectively. Further analysis showed that the mean survival and the median survival of the 36 patients in early years were 17.2 ± 9.7 months and 15 months, in contrast to 23.4 ± 11.3 months and 18 months of the 28 patients in recent years. CONCLUSION: Pleuropneumonectomy is an option of patients with advanced-stage lung cancer associated with uncontrolled malignant pleural fluid by conservative therapies. Strict selection of patient to be operated, careful procedures to eradicate obvious tumors and metastasis and enhanced post-operative combined therapy are beneficial to patients' long-term survival.

The novel pro-osteogenic activity of NUCB2(1-83.).

NUCB2¹â»8³ has been recently reported as an anorexigenic and anti-hyperglycemic peptide. Here we report that NUCB2¹â»8³ promotes osteogenesis. It was found after two months of once-a-day intravenous injection of NUCB2¹â»8³, bone mineral density of femora and lumbar vertebrae were increased in ovariectomized rats. NUCB2¹â»8³ also increased the alkaline phosphatase activity and promoted mineralization in mouse MC3T3-E1 preosteoblastic cell line. When either both Arg6° and Arg6³ or Ser7² were mutated to Ala, the pro-osteogenic activity was completely lost, indicating that these residues are structurally important for its biological function. Furthermore, it encumbered osteoclastic differentiation of RAW 264.7 macrophage. It also excluded any possibility of the effect caused by contaminants or experimental faults, and demonstrated that the pro-osteogenic activity observed was a specific effect of NUCB2¹â»8³ itself. These findings warranted that further studies on NUCB2¹â»8³ would be valuable for the treatment of bone metabolic diseases especially for osteoporosis.