Long-Acting Strategies for Antibody Drugs: Structural Modification, Controlling Release, and Changing the Administration Route.

Because of their high specificity, high affinity, and targeting, antibody drugs have been widely used in the treatment of many diseases and have become the most favored new drugs for research in the world. However, some antibody drugs (such as small-molecule antibody fragments) have a short half-life and need to be administered frequently, and are often associated with injection-site reactions and local toxicities during use. Increasing attention has been paid to the development of antibody drugs that are long-acting and have fewer side effects. This paper reviews existing strategies to achieve long-acting antibody drugs, including modification of the drug structure, the application of drug delivery systems, and changing their administration route. Among these, microspheres have been studied extensively regarding their excellent tolerance at the injection site, controllable loading and release of drugs, and good material safety. Subcutaneous injection is favored by most patients because it can be quickly self-administered. Subcutaneous injection of microspheres is expected to become the focus of developing long-lasting antibody drug strategies in the near future.

Improving the formation probability and stability of noise-like pulse by weakening the spectrum filtering effect.

Noise-like pulses (NLP) are extremely sought after in low-coherence tomography and supercontinuum, etc. Here, we propose an effective method to form the NLP in the all-normal-dispersion (ANDi) fiber laser by weakening the spectrum filtering for the first time. Numerical explorations are performed in detail and demonstrate that the NLP can be originated from the clustering behavior of amplified random sub-pulses led by the saturable absorber. By simulating the pulse-pattern distribution in the two-dimensional parameter space, it is further found that this kind of NLP pattern is widely distributed where are with a weak spectrum filtering. Since, the weaker the filtering, the harder the dissipative system to achieve balance, which helps to avoid the evolution from the pulse cluster to other coherent states and supports the NLP stability. To prove the feasibility experimentally, we built an ANDi fiber laser based on the nonlinear polarization rotating (NPR). The built laser can operate at the stable dissipative soliton (DS) state with a spectrum filter, which also with a 45 nm wavelength tuning performance. Replacing the filter, only NLP with a 40.2 ps pedestal and 237 fs spike can be attained. The experiments agree well with the numerical predictions. This exploration significantly broadens the design possibilities for ultrafast lasers, making them much more accessible to produce desired pulse patterns.

All-fiber passively Q-switched laser with flat-top beam emissions.

Flat-top beams have plenty of applications in theoretical and applied research, but they are not eigenmodes of the wave equation. Here, we propose an effective strategy for generating flat-top beams in fibers, which originates from the incoherent superposition of orbital angular momentum (OAM) and fundamental (LP01) modes. The designed all-fiber passively Q-switched laser can realize high-quality pulsed flat-top and OAM beam emissions. The normalized root mean square of the flat-top beam is around 4.7%, and the purity of the OAM mode is calculated to be higher than 98%. For the first time to the best of our knowledge, pulsed emission of a flat-top beam is achieved using an all-fiber laser. Moreover, its repetition rate and duration can be controlled by adjusting the pump.

PARP-1 inhibition attenuates the inflammatory response in the cartilage of a rat model of osteoarthritis.

AIMS: Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. METHODS: The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. CONCLUSION: PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401-410.

Clinical efficacy of PVP and PKP in the treatment of OVCFs after bilateral resection of ovarian cancer.

The clinical efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures after bilateral resection of ovarian cancer was investigated. Eighty-six patients with osteoporotic vertebral compression fractures after bilateral resection of ovarian cancer admitted to the Second People's Hospital of Hefei from September, 2015 to August, 2016 were selected and randomly divided into control group (n=43) and observation group (n=43). The control group was treated with PVP, while the observation group received PKP. The operation time, fluoroscopy times, bone cement volume and leakage rate of patients in the two groups were recorded; the postoperative pain of patients was compared using Short-form McGill Pain Questionnaire; the changes in height of injured vertebra and Cobb angle of patients in two groups were compared; the efficacy of patients in the two groups was compared in accordance with Oswestry dysfunction index (ODI) and Japanese Orthopedic Association (JOA) low back pain scoring; and the quality of life was compared. The fluoroscopy times and bone cement leakage were significantly less in observation group than those in control group (P<0.05). After operation, the scores of ODI, MPQ and JOA in the two groups were significantly improved (P<0.05). The postoperative height of injured vertebra and the Cobb angle of patients in two groups were significantly different than those before the operation (P<0.05). The quality of life of patients in the observation group was higher than that in the control group one year after operation (P<0.05). In conclusion, PKP and PVP are effective in the treatment of osteoporotic vertebral compression fractures after bilateral resection of ovarian cancer; however, PKP is more conducive to lumbar stability and maintenance of intervertebral height thus greatly correcting the kyphosis, which is beneficial to improving the quality of life of patients.

The Roles of Feedback and Feedforward as Humans Learn to Control Unknown Dynamic Systems.

We present results from an experiment in which human subjects interact with an unknown dynamic system 40 times during a two-week period. During each interaction, subjects are asked to perform a command-following (i.e., pursuit tracking) task. Each subject's performance at that task improves from the first trial to the last trial. For each trial, we use subsystem identification to estimate each subject's feedforward (or anticipatory) control, feedback (or reactive) control, and feedback time delay. Over the 40 trials, the magnitudes of the identified feedback controllers and the identified feedback time delays do not change significantly. In contrast, the identified feedforward controllers do change significantly. By the last trial, the average identified feedforward controller approximates the inverse of the dynamic system. This observation provides evidence that a fundamental component of human learning is updating the anticipatory control until it models the inverse dynamics.