A value-based deep reinforcement learning model with human expertise in optimal treatment of sepsis.

Deep Reinforcement Learning (DRL) has been increasingly attempted in assisting clinicians for real-time treatment of sepsis. While a value function quantifies the performance of policies in such decision-making processes, most value-based DRL algorithms cannot evaluate the target value function precisely and are not as safe as clinical experts. In this study, we propose a Weighted Dueling Double Deep Q-Network with embedded human Expertise (WD3QNE). A target Q value function with adaptive dynamic weight is designed to improve the estimate accuracy and human expertise in decision-making is leveraged. In addition, the random forest algorithm is employed for feature selection to improve model interpretability. We test our algorithm against state-of-the-art value function methods in terms of expected return, survival rate, action distribution and external validation. The results demonstrate that WD3QNE obtains the highest survival rate of 97.81% in MIMIC-III dataset. Our proposed method is capable of providing reliable treatment decisions with embedded clinician expertise.

Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease.

Nowadays, it is still quite challenging to achieve an early diagnosis of the Alzheimer disease (AD) in clinics. The burgeoning near-infrared fluorescence (NIRF) imaging fulfills the requirements for a precise diagnosis with good sensitivity and a high signal-to-background ratio and offers opportunities for the efficient AD diagnosis. As the pathogenesis of AD is quite complex, there is an ongoing exploration of advanced probes to specifically target AD biomarkers (e.g., amyloid-ß (Aß) plaques, neurofibrillary tangles, viscosity, peroxynitrite (ONOO-), reactive oxygen species, and methylglyoxal). To this end, a great number of small molecular fluorescent probes with good water solubility, blood-brain barrier crossing capability, and ease in tuning photophysical and biological properties have been studied for the AD diagnosis. Herein, we systematically update the progress of NIRF AD probes in the last three years. The special focus is on the mechanisms for the targeted diagnosis and the relationship between the structure and properties of the probes. Importantly, NIRF probes with complementary functions such as dual-responsiveness and multimodal imaging and even therapeutics are discussed. Moreover, the challenges and perspectives of the AD probes are briefly elucidated. We hope that this review provides guidance for researchers and expedites the preclinical and clinical study of the NIRF AD probes.

Optical design of an integrated imaging system of optical camera and synthetic aperture radar.

This paper presents an integrated imaging system of optical camera and synthetic aperture radar (SAR). The system can realize 400 nm-900 nm visible and near infrared band and 35 GHz microwave Ka band dual-band imaging. Compared with the single band imaging system, the observation ability and environmental adaptability of the integrated imaging system have been significantly improved. The optical camera shares a common front system with the synthetic aperture radar. After simulation, the average modulation transfer function (MTF) of 50 line pairs per millimeter (lp/mm) of the optical subsystem is 0.47. In addition, a principle prototype with a pupil diameter of 210 mm was developed to verify the performance of synthetic aperture radar antennas. After the experimental test, the SAR radiation pattern simulation results are in good conformity with the measured results, which are in line with the expected results.

Separation of polysaccharides from Spirulina platensis by HSCCC with ethanol-ammonium sulfate ATPS and their antioxidant activities.

Three separation methods for water-soluble polysaccharides from Spirulina platensis (PSP) were compared, including sevage deproteinization and column chromatography, ethanol-ammonium sulfate aqueous two-phase system (ATPS) and column chromatography, and one-step high speed counter-current chromatography (HSCCC) with ethanol-ammonium sulfate ATPS. ATPS was confirmed as an efficient alternative method of protein removal for PSP purification. For the HSCCC with ethanol-ammonium sulfate ATPS, the stationary retention reached to 50.8% at the optimized rotation speed and flow rate. Moreover, the yield of PSP purified by one-step HSCCC rose nearly five times to 12.45mg/g(dry algae powder), it was higher than PSP yield by two-step column chromatography separation methods. PSP purified by HSCCC has the same purity as PSP obtained by traditional methods, which was proved by a single symmetrical peak of purified PSP with molecular weight of 12.33kDa through gel chromatography. Purified PSP was an α-acidic polysaccharide, composed of major glucose, slight rhamnose and mannose, which were detected within GC and FT-IR spectra. The antioxidation activity experiment showed that HSCCC-purified PSP had strong scavenging effects on hydroxyl free radical and DPPH free radical.

Cryopreserved ovarian tissues can maintain a long-term function after heterotopic autotransplantation in rat.

The functional longevity of cryopreserved ovarian grafts is one of the most challenging questions regarding ovarian transplantation at present. This study used a rat ovarian grafting model to investigate whether ovarian tissues from adult rats, which had been cryopreserved by vitrification and followed by heterotopic transplantation, could establish long-term hormone secretion and follicle development. Fresh and cryopreserved ovarian tissues were autologously transplanted under the kidney capsule. One-third of the animals in each group (sham-operated, fresh autografts, cryopreserved autografts, or castrated) were killed 5, 8, or 10 months after transplantation. Vaginal cytology, serum estradiol (E(2)), progesterone, and the morphology of the reproductive tract were used to assess ovarian function. Both fresh and cryopreserved ovarian grafts survived well in all the animal models with comparable proportion of follicles at each stage of folliculogenesis at all three time points. The serum E(2) and progesterone concentrations in the groups with fresh or cryopreserved grafts remained comparable with those in sham-operated controls at all investigated time points. However, a loss of grafts and primordial follicles following heterotopic transplantation was noted. In conclusion, the heterotopic autotransplantation of vitrified ovarian tissues from adult rat without vascular anastomosis can maintain long-term ovarian function and exert endocrine function in target organs, in spite of the reduction in follicle pool.

Activation of human embryonic gene expression in cytoplasmic hybrid embryos constructed between bovine oocytes and human fibroblasts.

Cross-species somatic all number transfer (SCNT) provides a potential solution to overcome the problem of oocyte shortage for therapeutic cloning. To further characterize the system, we constructed cytoplasm hybrid embryos between bovine oocytes and human fibroblasts and examined dynamics of human gene activation during preimplantation stages. Data from this study showed that human embryonic genes, OCT4, SOX2, NANOG, E-CADHERIN, as well as beta-ACTIN, were activated by enucleated bovine oocytes. Activation of human genes was correlated with developmental potential of the embryos. The extent of human gene activation varied drastically and was incomplete in a large proportion of the embryos. Activation of human genes in the human-bovine cytoplasm hybrid embryos occurs in a temporal pattern resembling that of the bovine species. Results from this study suggest that human gene products are required for hybrid embryos to develop to later preimplantation stages. Facilitating human genome activation may improve successful rates in cross-species SCNT.

Cloning of Asian yellow goat (C. hircus) by somatic cell nuclear transfer: telophase enucleation combined with whole cell intracytoplasmic injection.

Our and other previous studies have shown that telophase enucleation is an efficient method for preparing recipient cytoplasts in nuclear transfer. Conventional methods of somatic cell nuclear transfer either by electro-fusion or direct nucleus injection have very low efficiency in animal somatic cell cloning. To simplify the manipulation procedure and increase the efficiency of somatic cell nuclear transfer, this study was designed to study in vitro and in vivo development of Asian yellow goat cloned embryos reconstructed by direct whole cell intracytoplasmic injection (WCICI) into in vitro matured oocytes enucleated at telophase II stage. Our results demonstrated that the rates of cleavage and blastocyst development of embryos reconstructed by WCICI were slightly higher than in conventional subzonal injection (SUZI) group, but no statistic difference (P > 0.05) existed between these two methods. However, the percentage of successful embryonic reconstruction in WCICI group was significantly higher than that in SUZI group (P < 0.05). After embryo transfer at 4-cell stage, the foster in both groups gave birth to offspring. Therefore, the present study suggests that the telophase ooplasm could properly reprogram the genome of somatic cells, produce Asian yellow goat cloned embryos and viable kids, and whole cell intracytoplasmic injection is an efficient protocol for goat somatic cell nuclear transfer.

Interspecies nuclear transfer of Tibetan antelope using caprine oocyte as recipient.

Interspecies nuclear transfer is an invalulable tool for studying nucleus-cytoplasm interactions; and at the same time, it provides a possible alternative to clone endangered animals whose oocytes are difficult to obtain. In the present study, we investigated the possibility of cloning Tibetan antelope embryos using abattoir-derived caprine oocytes as recipients. Effects of culture conditions, enucleation timing, and donor cell passages on the in vitro development of Tibetan antelope-goat cloned embryos were studied. Maternal to zygotic transition timing of interspecies Tibetan antelope embryos was also investigated using two types of cloned embryos, Tibetan antelope-rabbit and Tibetan antelope-goat embryos. Our results indicate that: (1) goat oocyte is able to reprogram somatic cells of different genus and supports development to blastocyst in vitro. (2) Coculture system supported the development of Tibetan antelope-goat embryos to blastocyst rate stage (4.0%), while CR1aa alone did not. (3) When MII phase enucleated caprine cytoplast and TII phase enucleated caprine cytoplast were used as recipients, the fusion rate and blastocyst rate of hybrid embryos were not statistically different (73.9% vs. 67.4%; 4.0% vs. 1.1%). (4) When donor cells at 3-8 passages were used, 2.9% hybrid embryos developed to blastocysts, while none developed to blastocysts when cells at 10-17 passages were used. (5) There may be a morula-to-blastocyst block for Tibetan antelope-goat, while there may be an 8- to 16-cell block for Tibetan antelope-rabbit embryos.

Development of goat embryos reconstituted with somatic cells: the effect of cell-cycle coordination between transferred nucleus and recipient oocytes.

The developmental ability and the nucleus and microtubule dynamics of nuclear transplanted goat embryos derived from in vitro matured oocytes were studied while controlling cell-cycle coordination of donor embryonic nuclei and recipient cytoplasts. Three groups of transfers were studied: G0/G1 (after the fibroblast cells grew to 100% confluence) and G2/M (nocodazole treated) phase fibroblasts transferred to MII cytoplasts (G0/G1-->MII and G2/M-->MII group, respectively), and G0/G1 phase fibroblasts transferred to preactivated cytoplasts, mostly at S-phase, (G0/G1-->Pre group) by electrical fusion. The results showed that fusion and developmental ability did not differ between G0/G1-->MII and G0/G1-->Pre groups. However the developmental rate of embryos in the G0/G1-->MII group was significantly higher than that of the G2/M-->MII group. Most fibroblast nuclei (G0/G1 and G2/M) transferred into MII oocytes underwent premature chromosome condensation (PCC). Normal spindle were only detected in the G0/G1-->MII group. In contract, fibroblast nuclei in pre-activated oocytes rarely underwent PCC, but formed a swollen nuclear structure. The data suggest that in vitro matured goat oocytes can support the development of somatic fibroblasts after nuclear transfer, G0/G1 -->MII and G0/G1-->S nuclear transfer might be effective ways for improving the developmental competence of the reconstituted embryos, and that G2/M-->MII nuclear transfer by electrical fusion (even in Ca2+-free fusion medium) induces abnormal chromosome ploidy.