Therapeutic Effect of Vagus Nerve Stimulation on Depressive-Like Behavior, Hyperglycemia and Insulin Receptor Expression in Zucker Fatty Rats

Depression and type 2 diabetes (T2D) are common comorbid diseases and highly prevalent in the clinical setting with an unclarified mechanism. Zucker diabetic fatty (ZDF, fa/fa) rats natively develop T2D with hyperglycemia and hyperinsulinemia. Here we studied whether ZDF rats also innately develop depression, what a correlation is between depression and T2D, whether insulin receptor (IR) expression is involved in, and whether transcutaneous auricular vagus nerve stimulation (taVNS) would be beneficial in amelioration of the comorbidity. Six week old male ZDF and Zucker lean (ZL, fa/+) littermates were randomly divided into naïve (ZDF, n = 6; ZL, n = 7) and taVNS (ZDF-taVNS, n = 8; ZL-taVNS, n = 6) groups. Once daily 30 min-taVNS sessions were administrated under anesthesia for 34 consecutive days in taVNS groups. Blood glucose levels were tested weekly, and plasma glycosylated hemoglobin (HbAlc) level and immobility time in forced swimming test were determined on day 35 in all groups. The expression of insulin receptor (IR) in various tissues was also detected by immunostaining and Western blot. We found that naïve ZDF rats developed hyperglycemia steadily. These ZDF rats showed a strong positive correlation between longer immobility time and higher plasma HbAlC level. Long term taVNS treatment simultaneously prevented the development of depression-like behavior and progression of hyperglycemia in ZDF rats. The expression of IR in various tissues of naïve ZDF rats is lower than in naïve ZL and long-term taVNS treated ZDF rats. Collectively, our results indicate that in ZDF rats, i) depression and T2D develop simultaneously, ii) immobility time and HbAlc concentrations are highly and positively correlated, iii) a low expression of IR may be involved in the comorbidity of depression and T2D, and iv) taVNS is antidiabetic and antidepressive possibly through IR expression upregulation

Transcutaneous Auricular Vagus Nerve Stimulation Triggers Melatonin Secretion and Is Antidepressive in Zucker Diabetic Fatty Rats

Decreased circulating melatonin is implicated in depression. We recently found that Zucker diabetic fatty rats (ZDF, fa/fa) develop depression-like behaviors and that transcutaneous auricular vagus nerve stimulation (taVNS) is antidepressive in ZDF rats. Here we studied whether the ZDF rats could be used as a depression rodent model and whether the antidepressive effect of taVNS is mediated through modulation of melatonin secretion. Adult male ZDF and Zucker lean (ZL, fa/+) littermates were used. 30 min-taVNS procedures (2/15 Hz, 2 mA) were administered once daily under anesthesia for 34 consecutive days in pineal intact ZDF (n = 8) and ZL (n = 6) rats, as well as in pinealectomized ZDF rats (n = 8). Forced swimming test (FST) was used to determine depression-like behavior and ELISA to detect plasma melatonin concentration on day 35. We found that naïve ZDF rats had a longer immobility time in FST and that long-term (34 days) taVNS treatment ameliorated the depression-like behavior. In both pineal intact and pinealectomized ZDF rats, taVNS induced acute melatonin secretion, both during and after the taVNS session. A low melatonin level is related to the poor FST performance in ZDF rats (R = −0.544) in contrast to ZL rats (R = 0.247). In conclusion, our results show that ZDF rats are ideal candidates of innate depression and that taVNS is antidepressive through triggering melatonin secretion and increasing its production

Existence and Uniqueness of Solutions for a Type of Generalized Zakharov System

We study the Cauchy problem for a type of generalized Zakharov system. With the help of energy conservation and approximate argument, we obtain global existence and uniqueness in Sobolev spaces for this system. Particularly, this result implies the existence of classical solution for this generalized Zakharov system

Development and Validation of a Mutational Burden-Associated LncRNA Signature for Improving the Clinical Outcome of Hepatocellular Carcinoma

Background: Long non-coding RNAs (lncRNAs) modulate numerous cellular processes, including DNA damage repair. Here, we investigated the clinical importance of lncRNAs associated with mutational burden in hepatocellular carcinoma (HCC). Methods: Prognosis-related lncRNAs associated with mutational burden were screened and determined to score the mutational burden-associated lncRNA signature (MbLncSig) from TCGA. Prognostic values and predictive performance of the MbLncSig score were analysed. Results: Four mutational burden-associated lncRNAs (AC010643.1, AC116351.1, LUCAT1 and MIR210HG) were identified for establishing the MbLncSig score. The MbLncSig score served as an independent risk factor for HCC prognosis in different subgroup patients. The predictive performance of one-year and three-year OS was 0.739 and 0.689 in the entire cohort, respectively. Moreover, the MbLncSig score can further stratify the patient survival in those with TP53 wild type or mutation. Conclusions: This study identified a four-lncRNA signature (the MbLncSig score) which could predict survival in HCC patient with/without TP53 mutation

3D printing of self-healing personalized liver models for surgical training and preoperative planning

Abstract 3D printing can produce intuitive, precise, and personalized anatomical models, providing invaluable support for precision medicine, particularly in areas like surgical training and preoperative planning. However, conventional 3D printed models are often significantly more rigid than human organs and cannot undergo repetitive resection, which severely restricts their clinical value. Here we report the stereolithographic 3D printing of personalized liver models based on physically crosslinked self-healing elastomers with liver-like softness. Benefiting from the short printing time, the highly individualized models can be fabricated immediately following enhanced CT examination. Leveraging the high-efficiency self-healing performance, these models support repetitive resection for optimal trace through a trial-and-error approach. At the preliminary explorative clinical trial (NCT06006338), a total of 5 participants are included for preoperative planning. The primary outcomes indicate that the negative surgery margins are achieved and the unforeseen injuries of vital vascular structures are avoided. The 3D printing of liver models can enhance the safety of hepatic surgery, demonstrating promising application value in clinical practice

MBE Growth of High Electron Mobility InP Epilayers

The molecular beam epitaxial growth of high quality epilayers on （100） InP substrate using a valve phosphorous cracker cell over a wide range of P/In BEP ratio （2.0-7.0） and growth rate （0.437 and 0. 791μm/h）. Experimental results show that electrical properties exhibit a pronounced dependence on growth parameters,which are growth rate, P/In BEP ratio, cracker zone temperature, and growth temperature. The parameters have been optimized carefully via the results of Hall measurements. For a typical sample, 77K electron mobility of 4.57 × 10^4 cm^2/（V · s） and electron concentration of 1.55×10^15 cm^-3 have been achieved with an epilayer thickness of 2.35μm at a growth temperature of 370℃ by using a cracking zone temperature of 850℃

Rational design of a tripartite fusion protein of heparinase I enables one-step affinity purification and real-time activity detection

Enzymatic degradation of heparin has great potential as an ecological and specific way to produce low molecular weight heparin. However, the commercial use of heparinase I (HepA), one of the most important heparin lyases, has been hampered by low productivity and poor thermostability. Fusion with green fluorescent protein (GFP) or maltose-binding protein (MBP) has shown potential in facilitating the industrial use of HepA. Thus, tripartite fusion of GFP, MBP and HepA would be a promising approach. Therefore, in the present study, the tripartite fusion strategy was systematically studied, mainly focusing on the fusion order and the linker sequence, to obtain a fusion protein offering one-step purification and real-time detection of HepA activity by fluorescence as well as high HepA activity and thermostability. Our results show that fusion order is important for MBP binding affinity and HepA activity, while the linker sequences at domain junctions have significant effects on protein expression level, HepA activity and thermostability as well as GFP fluorescence. The best tripartite fusion was identified as MBP-(EAAAK)3-GFP-(GGGGS)3-HepA, which shows potential to facilitate the production of HepA and its application in industrial preparation of low molecular weight heparin

Combination of site-directed mutagenesis and calcium ion addition for enhanced production of thermostable MBP-fused heparinase I in recombinant Escherichia coli

Heparinase I (HepI), which specifically cleaves heparin and heparan sulfate, is one of the most extensively studied glycosaminoglycan lyases. Low productivity of HepI has largely hindered its industrial and pharmaceutical applications. Loss of bacterial HepI enzyme activity through poor thermostability during its expression and purification process in production can be an important issue. In this study, using a thermostabilization strategy combining site-directed mutagenesis and calcium ion addition during its production markedly improved the yield of maltose-binding protein-fused HepI (MBP–HepI) from recombinant Escherichia coli. Substitution of Cys297 to serine in MBP–HepI offered a 30.6 % increase in the recovered total enzyme activity due to a mutation-induced thermostabilizing effect. Furthermore, upon addition of Ca2+ as a stabilizer at optimized concentrations throughout its expression, extraction, and purification process, purified mutant MBP–HepI showed a specific activity of 56.3 IU/mg, 206 % higher than that of the wild type obtained without Ca2+ addition, along with a 177 % increase in the recovered total enzyme activity. The enzyme obtained through this novel approach also exhibited significantly enhanced thermostability, as indicated by both experimental data and the kinetic modeling. High-yield production of thermostable MBP–HepI using the present system will facilitate its applications in laboratory-scale heparin analysis as well as industrial-scale production of low molecular weight heparin as an improved anticoagulant substitute

Preparation of Large Volume Solid Argon Crystal and Its Feasibility Test as a Scintillation Material

An important background to the liquid argon detectors is that they are caused by the diffusion of radioactive isotopes in a scintillator (liquid phase). This radioactive isotope is produced in argon’s surrounding devices, such as circulation pipelines and liquid argon containers. The solid argon as a scintillation material in the detector can inhibit the diffusion and drift of radioactive isotopes in a solid phase scintillator. Additionally, the structure of a solid argon detector is simple and reduces the total source of radioactive background. In the CDEX-300 detection system, solid argon could substitute for liquid argon as the veto detector, preventing radioactive isotopes drifting to the central main detector (HPGe detectors array) surface to reduce backgrounds. Therefore, solid argon has great potential in the experiments since it is especially helpful to get the lower background in a larger active volume than liquid argon required in those low background detection experiments. This work introduces the preparation process and device of the large volume transparent crystalline argon, the acquisition of scintillation light, and the pulse amplitude spectrum of 137Cs obtained from a prototype detector of transparent solid argon crystal. The results show that the scheme proposed in this study can successfully produce a large volume transparent crystalline argon detector, the scintillation light signals can be effectively obtained from the solid argon scintillator, and the corresponding pulse amplitude spectrum is given. This work indicates that it is feasible to develop a solid argon crystal scintillation detector by using our approach