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BACKGROUND: Prostate cancer is one of the most common malignant tumors worldwide, and is the third-leading cause of cancer death in men. Nearly 70% of new prostate cancer patients in China are locally advanced or widely metastatic with poor prognosis. Providing active treatment to early stage prostate cancer patients can improve the prognosis of prostate cancer patients. Thus, this study sought to evaluate the economy of early prostate specific antigen (PSA) screening for high-risk prostate cancer. METHODS: Based on the data collected from the PSA screening activities of 11 county hospitals from October 2019 to April 2021, this study evaluated a high-risk prostate cancer population who received PSA screening and their quality of life and economy. The screening population comprised males aged over 50 years. All screening patients were tested for PSA. If the PSA value is unnormal, a further diagnosis based on magnetic resonance imagining (MRI) or a transrectal ultrasound-guided prostate biopsy were performed. The decision-tree and Markov model was used to simulate the process of disease development of high-risk prostate cancer patients who underwent screenings and those who did not, and the incremental cost-effectiveness ratio was also evaluated. RESULTS: A total of 13,726 men received a PSA screening. Of these, 1,062 men had abnormal PSA values, and 73 of these were diagnosed with prostate cancer. Of these 73 patients, 40, 21, and 12 had early stage, mid-stage, and late-stage prostate cancer, respectively. Compared to the patients unscreened, the 1,000 patients who received an early PSA screening increased their quality-adjusted life year (QALY) by 15.69 years; however, each QALY had an additional cost of 38,550 yuan, which was lower than the willingness to pay threshold of 72,447 yuan (per capita gross domestic product in 2020). CONCLUSIONS: For high-risk prostate cancer patients, early screenings have a cost-effective advantage over no screenings. Thus, early screening should be vigorously promoted for high-risk prostate cancer patients.

In insects, odorant receptors facilitate olfactory communication and require the functionality of the highly conserved co-receptor gene orco. Genome editing studies in a few species of ants and moths have revealed that orco can also have a neurodevelopmental function, in addition to its canonical role in adult olfaction, discovered first in Drosophila melanogaster. To extend this analysis, we determined whether orco mutations also affect the development of the adult brain of the honey bee Apis mellifera, an important model system for social behavior and chemical communication. We used CRISPR/Cas9 to knock out orco and examined anatomical and molecular consequences. To increase efficiency, we coupled embryo microinjection with a laboratory egg collection and in vitro rearing system. This new workflow advances genomic engineering technologies in honey bees by overcoming restrictions associated with field studies. We used Sanger sequencing to quickly select individuals with complete orco knockout for neuroanatomical analyses and later validated and described the mutations with amplicon sequencing. Mutant bees had significantly fewer glomeruli, smaller total volume of all the glomeruli, and higher mean individual glomerulus volume in the antennal lobe compared to wild-type controls. RNA-Sequencing revealed that orco knockout also caused differential expression of hundreds of genes in the antenna, including genes related to neural development and genes encoding odorant receptors. The expression of other types of chemoreceptor genes was generally unaffected, reflecting specificity of CRISPR activity in this study. These results suggest that neurodevelopmental effects of orco are related to specific insect life histories.

In insects, odorant receptors facilitate olfactory communication and require the functionality of the highly conserved co-receptor gene

Wiring up the eye During development, sensory systems must build topographic maps by connecting neurons at different levels within a circuit. Fernandes et al. now open a window into how the Drosophila eye develops these maps (see the Perspective by Isaacman-Beck and Clandinin). The authors show that glial cells that ensheath axons relay cues from photoreceptors to induce the differentiation of the photoreceptor target field—the so-called lamina neurons—in the Drosophila visual system. Thus, glia can play an instructive role in differentiation, helping to direct the spatiotemporal patterning of neurogenesis. Science , this issue p. 886 ; see also p. 867

Over 600 Myr of evolutionary divergence between vertebrates and invertebrates is associated with considerable neuroanatomical variation both across and within these lineages. By contrast, valence encoding is an important behavioural trait that is evolutionarily conserved across vertebrates and invertebrates, and enables individuals to distinguish between positive (potentially beneficial) and negative (potentially harmful) situations. We tested the hypothesis that social interactions of positive and negative valence are modularly encoded in the honeybee brain (i.e. encoded in different cellular subpopulations) as in vertebrate brains. In vertebrates, neural activation patterns are distributed across distinct parts of the brain, suggesting that discrete circuits encode positive or negative stimuli. Evidence for this hypothesis would suggest a deep homology of neural organization between insects and vertebrates for valence encoding, despite vastly different brain sizes. Alternatively, overlapping localization of valenced social information in the brain would imply a ‘re-use' of circuitry in response to positive and negative social contexts, potentially to overcome the energetic constraints of a tiny brain. We used immediate early gene expression to map positively and negatively valenced social interactions in the brain of the western honeybeeApis mellifera. We found that the valence of a social signal is represented by distinct anatomical subregions of the mushroom bodies, an invertebrate sensory neuropil associated with social behaviour, multimodal sensory integration, learning and memory. Our results suggest that the modularization of valenced social information in the brain is a fundamental property of neuroanatomical organization.

SUMMARY How neuronal and glial fates are specified from neural precursor cells is an important question for developmental neurobiologists. We address this question in the Drosophila optic lobe, composed of the lamina, medulla, and lobula complex. We show that two gliogenic regions posterior to the prospective lamina also produce lamina wide-field (Lawf) neurons, which share common progenitors with lamina glia. These progenitors express neither canonical neuroblast nor lamina precursor cell markers. They bifurcate into two sub-lineages in response to Notch signaling, generating lamina glia or Lawf neurons, respectively. The newly born glia and Lawfs then migrate tangentially over substantial distances to reach their target tissue. Thus, Lawf neurogenesis, which includes a common origin with glia, as well as neuronal migration, resembles several aspects of vertebrate neurogenesis., Graphical abstract

Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the

Summary Neural circuit formation relies on interactions between axons and cells within the target field. While it is well established that target-derived signals act on axons to regulate circuit assembly, the extent to which axon-derived signals control circuit formation is not known. In the Drosophila visual system, anterograde signals numerically match R1–R6 photoreceptors with their targets by controlling target proliferation and neuronal differentiation. Here we demonstrate that additional axon-derived signals selectively couple target survival with layer specificity. We show that Jelly belly (Jeb) produced by R1–R6 axons interacts with its receptor, anaplastic lymphoma kinase (Alk), on budding dendrites to control survival of L3 neurons, one of three postsynaptic targets. L3 axons then produce Netrin, which regulates the layer-specific targeting of another neuron within the same circuit. We propose that a cascade of axon-derived signals, regulating diverse cellular processes, provides a strategy for coordinating circuit assembly across different regions of the nervous system.

International audience; In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neuron, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar neurons contact multiple columns. Here we show that combinatorial inputs from temporal and spatial axes generate this neuronal diversity: all neuroblasts switch fates over time to produce different neurons; the neuroepithelium that generates neuroblasts is also subdivided into six compartments by the expression of specific factors. Uni-columnar neurons are produced in all spatial compartments independently of spatial input; they innervate the neuropil where they are generated. Multi-columnar neurons are generated in smaller numbers in restricted compartments and require spatial input; the majority of their cell bodies subsequently move to cover the entire medulla. The selective integration of spatial inputs by a fixed temporal neuroblast cascade thus acts as a powerful mechanism for generating neural diversity, regulating stoichiometry and the formation of retinotopy.

Summary A fundamental question in developmental neuroscience is how a collection of progenitor cells proliferates and differentiates to create a brain of the appropriate size and cellular composition. To address this issue, we devised lineage-tracing assays in developing zebrafish embryos to reconstruct entire retinal lineage progressions in vivo and thereby provide a complete quantitative map of the generation of a vertebrate CNS tissue from individual progenitors. These lineage data are consistent with a simple model in which the retina is derived from a set of equipotent retinal progenitor cells (RPCs) that are subject to stochastic factors controlling lineage progression. Clone formation in mutant embryos reveals that the transcription factor Ath5 acts as a molecular link between fate choice and mode of cell division, giving insight into the elusive molecular mechanisms of histogenesis, the conserved temporal order by which neurons of different types exit the cell cycle., Highlights ► Method for full live lineage tracing of retinal cells in vivo ► Demonstration that retinal clone growth is representative of retinal growth ► A stochastic model accurately predicts clone growth from equipotent progenitors ► Links between mode of cell division and cell fate help explain histogenesis, A key question in developmental neuroscience is how a collection of progenitors proliferates and differentiates to create a brain of the consistent size and composition. He et al. use lineage tracing to reconstruct the full retinal lineages in vivo and propose a model for stochastic control of lineage progression.

Information processing relies on precise patterns of synapses between neurons. The cellular recognition mechanisms regulating this specificity are poorly understood. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Here, we sought to identify candidate cell recognition molecules underlying this specificity. Using RNA sequencing (RNA-seq), we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA-seq and protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig-containing proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity.

Background. PG27 is an immunosuppressive fraction purified from an extract of a Chinese medicinal plant Tripterygium wilfordii, which we investigated alone and in combination with cyclosporine (CsA) in a concordant, hamster-to-rat cardiac xenotransplantation model. Methods. Golden Syrian hamster hearts were heterotopically transplanted into the abdomen of Lewis rat recipients, which were treated intraperitoneally or orally with PG27, CsA, or both. Results. Combination therapy with 30 mg/kg/day of PG27 and CsA at 10 mg/kg/day successfully suppressed acute hamster-to-rat cardiac xenograft rejection. Treatment with PG27 or CsA alone was ineffective. Among several effective combinations, the best regimen involved PG27 at 30 mg/kg/day and CsA at 5 mg/ kg/day from days 8 to 35 and then CsA at 5 mg/kg/day from days 36 to 100, which produced 100% survival beyond 100 days. CsA suppressed the heterospecific lymphocytotoxic antibody response and inhibited IgG but not IgM xenoantibody production (which led to xenograft rejection), whereas PG27 alone did not prevent antibody production. The PG27/CsA combination blocked the lymphocytotoxic antibody response and IgG and IgM xenoantibody production induced by cardiac xenotransplantation. Conclusions. PG27 combined with CsA substantially prolonged hamster-to-rat cardiac xenograft survival, as well as completely inhibiting xenoantibody production.

Drosophila has recently become a powerful model system to understand the mechanisms of temporal patterning of neural progenitors called neuroblasts (NBs). Two different temporal sequences of transcription factors (TFs) have been found to be sequentially expressed in NBs of two different systems: the Hunchback, Kruppel, Pdm1/Pdm2, Castor, and Grainyhead sequence in the Drosophila ventral nerve cord; and the Homothorax, Klumpfuss, Eyeless, Sloppy-paired, Dichaete, and Tailless sequence that patterns medulla NBs. In addition, the intermediate neural progenitors of type II NB lineages are patterned by a different sequence: Dichaete, Grainyhead, and Eyeless. These three examples suggest that temporal patterning of neural precursors by sequences of TFs is a common theme to generate neural diversity. Cross-regulations, including negative feedback regulation and positive feedforward regulation among the temporal factors, can facilitate the progression of the sequence. However, there are many remaining questions to understand the mechanism of temporal transitions. The temporal sequence progression is intimately linked to the progressive restriction of NB competence, and eventually determines the end of neurogenesis. Temporal identity has to be integrated with spatial identity information, as well as with the Notch-dependent binary fate choices, in order to generate specific neuron fates.

In the Drosophila optic lobes, the medulla processes visual information coming from inner photoreceptors R7 and R8 and from lamina neurons. It contains approximately 40,000 neurons belonging to more than 70 different types. Here we describe how precise temporal patterning of neural progenitors generates these different neural types. Five transcription factors-Homothorax, Eyeless, Sloppy paired, Dichaete and Tailless-are sequentially expressed in a temporal cascade in each of the medulla neuroblasts as they age. Loss of Eyeless, Sloppy paired or Dichaete blocks further progression of the temporal sequence. We provide evidence that this temporal sequence in neuroblasts, together with Notch-dependent binary fate choice, controls the diversification of the neuronal progeny. Although a temporal sequence of transcription factors had been identified in Drosophila embryonic neuroblasts, our work illustrates the generality of this strategy, with different sequences of transcription factors being used in different contexts.

To improve communication reliability and protocols'portability on the nodes of wireless sensor network and ease the development difficulty, a new system design scheme based on the embedded operating system μC/OS-II is proposed in this paper. According to operating system modular design strategy, the way of task partitioning for network protocol stack is present and the operating system is transplanted on the LPC2138. An analysis about error data acknowledgement on data link layer was also put up, together with a corresponding improvement. The experiment shows that, basing on the operating system, the protocol stack runs smoothly, reliably. What's more, the platform meets the applications of location etc.

Background. PG27 is an active fraction purified from an extract of a Chinese medicinal plant, Tripterygium wilfordii Hook f. We tested PG27 in murine allogeneic bone marrow transplantation (BMT) and investigated the mechanism of graft-versus-host disease (GVHD) suppression. Methods. Recipients in the C57BL/6 → BDF1 murine BMT model received oral or intraperitoneal PG27. Results. Fourteen days of PG27 given orally or intraperitoneally prevented GVHD development and produced extended disease-free survival (more than 300 days) for many animals. PG490-88, a semisynthetic derivative of PG490 (triptolide, present in PG27), was also efficacious. PG27 reduced day 7 splenic allospecific cytotoxic T lymphocyte levels by more than 99% compared with vehicle-treated mice. Compared with normals, spleens from control allogeneic BMT mice displayed significantly reduced mononuclear cell content, an increased percentage of CD8+ cells, fewer CD4+ cells, and more activated ([interleukin-2 receptor+], IL-2R+) CD8+ T cells. PG27 increased mononuclear cell recovery, and significantly reduced the day-14 percentages of CD3+ and IL-2R+ cells in allogeneic BMT mice, producing results similar to those for syngeneic BMT mice. PG27 significantly increased concanavalin A-stimulated in vitro IL-4 production by day-14 splenocytes, with a 7- to 8-fold higher level than that produced by control cells. Conclusions. PG27 treatment for only 14 days prevented GVHD induction and development and produced long-term survival. PG27 largely normalized splenic T lymphocyte subsets, reduced allospecific cytotoxic T lymphocyte activity, and increased IL-4 production capability. PG27 may suppress GVHD by the induction of anergy and a deviation away from a proinflammatory phenotype, which could be reflected in the increased potential for IL-4 production.

Background PG27 is an immunosuppressive fraction purified from an extract of a Chinese medicinal plant, Tripterygium wilfordii. We tested PG27 in rat cardiac and renal allotransplantation, and we examined the immunosuppressive interaction with cyclosporine (CsA). Methods Brown Norway (BN) rat heart or kidney allografts were transplanted into the abdomen of Lewis rats, which were treated by the intraperitoneal or oral route with PG27, CsA, or both. Results PG27 administered intraperitoneally to Lewis recipients for 16 days at 10-30 mg/kg/day significantly increased the median survival time of BN heart allografts from 7 to 18-22 days. Oral administration was effective, with cardiac allograft survival prolonged to > 100 days with 52 days of treatment. PG27 at 20-30 mg/kg/day significantly extended the median survival time of BN kidney allograft recipients from 9 to 36.5-77 days, and 30 mg/kg/day for 52 days extended survival beyond 200 days. PG27 combined with CsA significantly enhanced heart and kidney allograft survival, even at doses of CsA ineffective when administered alone. The addition of 5 or 10 mg/kg/day PG27 reduced by 50-75% the CsA dose needed for 100% kidney allograft survival. The combination index was less than 1.0, indicating synergy of PG27 with CsA in prolonging cardiac and renal allograft survival. Furthermore, the PG27/CsA combination exerted a positive influence on renal allograft function. PG490 (triptolide, a constituent of PG27) and PG490-88 (a semisynthetic derivative of PG490) suppressed rejection of cardiac and renal allografts. Conclusions The PG27 herbal extract demonstrated immunosuppressive activity by prolonging heart and kidney allograft survival, displaying synergy in the immunosuppressive interaction with CsA, and improving renal allograft function in combination with CsA. PG490 and PG490-88 compounds were also effective.