Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review

Diabetes is a chronic metabolic disease, and its therapeutic goals focus on the effective management of blood glucose and various complications. Drug combination therapy has emerged as a comprehensive treatment approach for diabetes. An increasing number of studies have shown that, compared with monotherapy, combination therapy can bring significant clinical benefits while controlling blood glucose, weight, and blood pressure, as well as mitigating damage from certain complications and delaying their progression in diabetes, including both type 1 diabetes (T1D), type 2 diabetes (T2D) and related complications. This evidence provides strong support for the recommendation of combination therapy for diabetes and highlights the importance of combined treatment. In this review, we first provided a brief overview of the phenotype and pathogenesis of diabetes and discussed several conventional anti-diabetic medications currently used for the treatment of diabetes. We then reviewed several clinical trials and pre-clinical animal experiments on T1D, T2D, and their common complications to evaluate the efficacy and safety of different classes of drug combinations. In general, combination therapy plays a pivotal role in the management of diabetes. Integrating the effectiveness of multiple drugs enables more comprehensive and effective control of blood glucose without increasing the risk of hypoglycemia or other serious adverse events. However, specific treatment regimens should be tailored to individual patients and implemented under the guidance of healthcare professionals

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

A PAM4 transceiver design scheme with threshold adaptive and tap adaptive

Abstract To meet the demand of low bit error rate and high bandwidth for high-speed links, a reliable 112 Gb/s four-level pulse amplitude modulation (PAM4) transceiver design scheme with adaptive threshold voltage and adaptive decision feedback equalizer is proposed in this paper. In this scheme, three continuous time linear equalizers (CTLEs) at the front end of receiver are used to compensate the high-frequency, mid-frequency and low-frequency signals, respectively, and the variable gain amplifier (VGA) and saturation amplifier (SatAmp) are used to scale the signal amplitude. In addition to the three data samplers, four auxiliary samplers are also used for threshold adaptation. The sign-sign least mean squares algorithm uses the offset between the data sampler and the auxiliary sampler at the receiver side to drive the auxiliary reference voltage to converge to the signal constellation level, thus ensuring that the eye diagram of the PAM4 received signal has equal spacing and a constant signal–noise ratio for the three eyes in the vertical direction. In addition, the adaptive DFE for PAM4 signaling allows the transceiver to better adapt to the channel and thus achieve better equalizer performance. The simulation results show that the PAM4 transceiver design can compensate up to 25 dB of channel loss with an average eye height of 59.6 mv and an average eye width of 0.27 UI at a bit error rate of 10−12 under the condition of 3-tap feedforward equalizer (FFE) transmitter

Low Overpotential in Vacancy-Rich Ultrathin CoSe₂ Nanosheets for Water Oxidation

According to Yang Shao-Horn’s principle, CoSe₂ is a promising candidate as an efficient, affordable, and sustainable alternative electrocatalyst for the oxygen evolution reaction, owing to its well-suited electronic configuration of Co ions. However, the catalytic efficiency of pure CoSe₂ is still far below what is expected, because of its poor active site exposure yield. Herein, we successfully overcome the disadvantage of insufficient active sites in bulk CoSe₂ by reducing its thickness into the atomic scale rather than any additional modification (such as doping or hybridizing with graphene or noble metals). The positron annihilation spectrometry and XAFS spectra provide clear evidence that a large number of V_Co″ vacancies formed in the ultrathin nanosheets. The first-principles calculations reveal that these V_Co″ vacancies can serve as active sites to efficiently catalyze the oxygen evolution reaction, manifesting an OER overpotential as low as 0.32 V at 10 mA cm^–2 in pH 13 medium, which is superior to the values for its bulk counterparts as well as those for the most reported Co-based electrocatalysts. Considering the outstanding performance of the simple, unmodified ultrathin CoSe₂ nanosheets as the only catalyst, further improvement of the catalytic activity is expected when various strategies of doping or hybridizing are used. These results not only demonstrate the potential of a notable, affordable, and earth-abundant water oxidation electrocatalyst based on ultrathin CoSe₂ nanosheets but also open up a promising avenue into the exploration of excellent active and durable catalysts toward replacing noble metals for oxygen electrocatalysis

The Design and Technology Development of the JUNO Central Detector

International audienceThe Jiangmen Underground Neutrino Observatory (JUNO) is a large scale neutrino experiment with multiple physics goals including deter mining the neutrino mass hierarchy, the accurate measurement of neutrino oscillation parameters, the neutrino detection from the super nova, the Sun, and the Earth, etc. JUNO puts forward physically and technologically stringent requirements for its central detector (CD), including a large volume and target mass (20 kt liquid scintillator, LS), a high energy resolution (3% at 1 MeV), a high light transmittance, the largest possible photomultiplier (PMT) coverage, the lowest possible radioactive background, etc. The CD design, using a spherical acrylic vessel with a diameter of 35.4 m to contain the LS and a stainless steel structure to support the acrylic vessel and PMTs, was chosen and optimized. The acrylic vessel and the stainless steel structure will be immersed in pure water to shield the radioactive back ground and bear great buoyancy. The challenging requirements of the acrylic sphere have been achieved, such as a low intrinsic radioactivity and high transmittance of the manufactured acrylic panels, the tensile and compressive acrylic node design with embedded stainless steel pad, one-time polymerization for multiple bonding lines. Moreover, several technical challenges of the stainless steel structure have been solved: the production of low radioactivity stainless steel material, the deformation and precision control during production and assembly, the usage of high strength stainless steel rivet bolt and of high friction efficient linkage plate. Finally, the design of the ancillary equipment like the LS filling, overflowing and circulating system was done

The Design and Technology Development of the JUNO Central Detector

International audienceThe Jiangmen Underground Neutrino Observatory (JUNO) is a large scale neutrino experiment with multiple physics goals including deter mining the neutrino mass hierarchy, the accurate measurement of neutrino oscillation parameters, the neutrino detection from the super nova, the Sun, and the Earth, etc. JUNO puts forward physically and technologically stringent requirements for its central detector (CD), including a large volume and target mass (20 kt liquid scintillator, LS), a high energy resolution (3% at 1 MeV), a high light transmittance, the largest possible photomultiplier (PMT) coverage, the lowest possible radioactive background, etc. The CD design, using a spherical acrylic vessel with a diameter of 35.4 m to contain the LS and a stainless steel structure to support the acrylic vessel and PMTs, was chosen and optimized. The acrylic vessel and the stainless steel structure will be immersed in pure water to shield the radioactive back ground and bear great buoyancy. The challenging requirements of the acrylic sphere have been achieved, such as a low intrinsic radioactivity and high transmittance of the manufactured acrylic panels, the tensile and compressive acrylic node design with embedded stainless steel pad, one-time polymerization for multiple bonding lines. Moreover, several technical challenges of the stainless steel structure have been solved: the production of low radioactivity stainless steel material, the deformation and precision control during production and assembly, the usage of high strength stainless steel rivet bolt and of high friction efficient linkage plate. Finally, the design of the ancillary equipment like the LS filling, overflowing and circulating system was done

The Design and Technology Development of the JUNO Central Detector

International audienceThe Jiangmen Underground Neutrino Observatory (JUNO) is a large scale neutrino experiment with multiple physics goals including deter mining the neutrino mass hierarchy, the accurate measurement of neutrino oscillation parameters, the neutrino detection from the super nova, the Sun, and the Earth, etc. JUNO puts forward physically and technologically stringent requirements for its central detector (CD), including a large volume and target mass (20 kt liquid scintillator, LS), a high energy resolution (3% at 1 MeV), a high light transmittance, the largest possible photomultiplier (PMT) coverage, the lowest possible radioactive background, etc. The CD design, using a spherical acrylic vessel with a diameter of 35.4 m to contain the LS and a stainless steel structure to support the acrylic vessel and PMTs, was chosen and optimized. The acrylic vessel and the stainless steel structure will be immersed in pure water to shield the radioactive back ground and bear great buoyancy. The challenging requirements of the acrylic sphere have been achieved, such as a low intrinsic radioactivity and high transmittance of the manufactured acrylic panels, the tensile and compressive acrylic node design with embedded stainless steel pad, one-time polymerization for multiple bonding lines. Moreover, several technical challenges of the stainless steel structure have been solved: the production of low radioactivity stainless steel material, the deformation and precision control during production and assembly, the usage of high strength stainless steel rivet bolt and of high friction efficient linkage plate. Finally, the design of the ancillary equipment like the LS filling, overflowing and circulating system was done

Mass Testing and Characterization of 20-inch PMTs for JUNO

Main goal of the JUNO experiment is to determine the neutrino mass ordering using a 20kt liquid-scintillator detector. Its key feature is an excellent energy resolution of at least 3 % at 1 MeV, for which its instruments need to meet a certain quality and thus have to be fully characterized. More than 20,000 20-inch PMTs have been received and assessed by JUNO after a detailed testing program which began in 2017 and elapsed for about four years. Based on this mass characterization and a set of specific requirements, a good quality of all accepted PMTs could be ascertained. This paper presents the performed testing procedure with the designed testing systems as well as the statistical characteristics of all 20-inch PMTs intended to be used in the JUNO experiment, covering more than fifteen performance parameters including the photocathode uniformity. This constitutes the largest sample of 20-inch PMTs ever produced and studied in detail to date, i.e. 15,000 of the newly developed 20-inch MCP-PMTs from Northern Night Vision Technology Co. (NNVT) and 5,000 of dynode PMTs from Hamamatsu Photonics K. K.(HPK)

The JUNO experiment Top Tracker

20 pagesInternational audienceThe main task of the Top Tracker detector of the neutrino reactor experiment Jiangmen Underground Neutrino Observatory (JUNO) is to reconstruct and extrapolate atmospheric muon tracks down to the central detector. This muon tracker will help to evaluate the contribution of the cosmogenic background to the signal. The Top Tracker is located above JUNO's water Cherenkov Detector and Central Detector, covering about 60% of the surface above them. The JUNO Top Tracker is constituted by the decommissioned OPERA experiment Target Tracker modules. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multianode photomultiplier tubes. Compared to the OPERA Target Tracker, the JUNO Top Tracker uses new electronics able to cope with the high rate produced by the high rock radioactivity compared to the one in Gran Sasso underground laboratory. This paper will present the new electronics and mechanical structure developed for the Top Tracker of JUNO along with its expected performance based on the current detector simulation