Acceleration of phosphorus weathering under warm climates.

The release of phosphorous (P) via chemical weathering is a vital process that regulates the global cycling of numerous key elements and shapes the size of the Earth's biosphere. It has long been postulated that global climate should theoretically play a prominent role in governing P weathering rates. Yet, there is currently a lack of direct evidence for this relationship based on empirical data at the global scale. Here, using a compilation of temperature and P content data of global surface soils (0 to 30 cm), we demonstrate that P release does enhance at high mean annual surface temperatures. We propose that this amplification of nutrient supply with warming is a critical component of Earth's natural thermostat, and that this relationship likely caused expanded oceanic anoxia during past climate warming events. The potential acceleration of phosphorus loss from soils due to anthropogenic climate warming may pose threats to agricultural production, terrestrial and marine ecosystems, and alter marine redox landscapes.

Accelerating SSSP for Power-Law Graphs.

The single-source shortest path (SSSP) problem is one of the most important and well-studied graph problems widely used in many application domains, such as road navigation, neural image reconstruction, and social network analysis. Although we have known various SSSP algorithms for decades, implementing one for large-scale power-law graphs efficiently is still highly challenging today, because ① a work-efficient SSSP algorithm requires priority-order traversal of graph data, ② the priority queue needs to be scalable both in throughput and capacity, and ③ priority-order traversal requires extensive random memory accesses on graph data. In this paper, we present SPLAG to accelerate SSSP for power-law graphs on FPGAs. SPLAG uses a coarse-grained priority queue (CGPQ) to enable high-throughput priority-order graph traversal with a large frontier. To mitigate the high-volume random accesses, SPLAG employs a customized vertex cache (CVC) to reduce off-chip memory access and improve the throughput to read and update vertex data. Experimental results on various synthetic and real-world datasets show up to a 4.9× speedup over state-of-the-art SSSP accelerators, a 2.6× speedup over 32-thread CPU running at 4.4 GHz, and a 0.9× speedup over an A100 GPU that has 4.1× power budget and 3.4× HBM bandwidth. Such a high performance would place SPLAG in the 14th position of the Graph 500 benchmark for data intensive applications (the highest using a single FPGA) with only a 45 W power budget. SPLAG is written in high-level synthesis C++ and is fully parameterized, which means it can be easily ported to various different FPGAs with different configurations. SPLAG is open-source at https://github.com/UCLA-VAST/splag.

Extending High-Level Synthesis for Task-Parallel Programs.

C/C++/OpenCL-based high-level synthesis (HLS) becomes more and more popular for field-programmable gate array (FPGA) accelerators in many application domains in recent years, thanks to its competitive quality of results (QoR) and short development cycles compared with the traditional register-transfer level design approach. Yet, limited by the sequential C semantics, it remains challenging to adopt the same highly productive high-level programming approach in many other application domains, where coarse-grained tasks run in parallel and communicate with each other at a fine-grained level. While current HLS tools do support task-parallel programs, the productivity is greatly limited ① in the code development cycle due to the poor programmability, ② in the correctness verification cycle due to restricted software simulation, and ③ in the QoR tuning cycle due to slow code generation. Such limited productivity often defeats the purpose of HLS and hinder programmers from adopting HLS for task-parallel FPGA accelerators. In this paper, we extend the HLS C++ language and present a fully automated framework with programmer-friendly interfaces, unconstrained software simulation, and fast hierarchical code generation to overcome these limitations and demonstrate how task-parallel programs can be productively supported in HLS. Experimental results based on a wide range of real-world task-parallel programs show that, on average, the lines of kernel and host code are reduced by 22% and 51%, respectively, which considerably improves the programmability. The correctness verification and the iterative QoR tuning cycles are both greatly shortened by 3.2× and 6.8×, respectively. Our work is open-source at https://github.com/UCLA-VAST/tapa/.

Danshensu inhibits the IL-1ß-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway.

PURPOSE: Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1ß is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1ß-induced inflammatory responses in OA. METHODS: IL-1ß was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. RESULTS: DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1ß treated chondrocytes. In addition, DSS downregulated IL-1ß-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1ß-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. CONCLUSIONS: Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

AutoBridge: Coupling Coarse-Grained Floorplanning and Pipelining for High-Frequency HLS Design on Multi-Die FPGAs.

Despite an increasing adoption of high-level synthesis (HLS) for its design productivity advantages, there remains a significant gap in the achievable frequency between an HLS design and a handcrafted RTL one. A key factor that limits the timing quality of the HLS outputs is the difficulty in accurately estimating the interconnect delay at the HLS level. This problem becomes even worse when large HLS designs are implemented on the latest multi-die FPGAs. To tackle this challenge, we propose AutoBridge, an automated framework that couples a coarse-grained floorplanning step with pipelining during HLS compilation. First, our approach provides HLS with a view on the global physical layout of the design, allowing HLS to more easily identify and pipeline the long wires, especially those crossing the die boundaries. Second, by exploiting the flexibility of HLS pipelining, the floorplanner is able to distribute the design logic across multiple dies on the FPGA device without degrading clock frequency. This prevents the placer from aggressively packing the logic on a single die which often results in local routing congestion that eventually degrades timing. Since pipelining may introduce additional latency, we further present analysis and algorithms to ensure the added latency will not compromise the overall throughput. AutoBridge can be integrated into the existing CAD toolflow for Xilinx FPGAs. In our experiments with a total of 43 design configurations, we improve the average frequency from 147 MHz to 297 MHz (a 102% improvement) with no loss of throughput and a negligible change in resource utilization. Notably, in 16 experiments we make the originally unroutable designs achieve 274 MHz on average. The tool is available at https://github.com/Licheng-Guo/AutoBridge.

Identification and expression of DoCCaMK during Sebacina sp. symbiosis of Dendrobium officinale.

Dendrobium officinale Kimura et Migo is a famous precious medicinal plant in China. Seed and seedling were cultivated with the mycorrhizal fungus Sebacina sp. CCaMK was initially cloned from D. officinale based on a SSH cDNA library of symbiotically germinated seeds with Sebacina sp. Phylogenetic analysis was performed among DoCCaMK and other CCaMKs. The particle bombardment technique was used to visualize DoCCaMK-GFP. qRT-PCR and western blot analysis were conducted to determine the tissue expression patterns of DoCCaMK with (SGS) and without (UGS) Sebacina sp. Furthermore, the effect of KN-93 on CCaMK expression was also examined. Using NMT the net Ca2+ fluxes and the CCaMK concentration were measured during D. officinale seed germination. DoCCaMK had the highest homology with Lilium longiflorum CCaMK. The DoCCaMK-GFP protein localized in the nucleus and cell membrane. CCaMK expression was significantly upregulated after symbiosis with Sebacina sp. KN-93 could be used as an inhibitor of CCaMK to inhibit D. officinale seed germination. Ca2+ influx and the concentration of the CCaMK in the SGS group was significantly more than that of the UGS group. The characterization of CCaMK provides certain genetic evidence for the involvement of this gene during seed germination and mycorrhizal cultivation in D. officinale.

miR-125b acts as anti-fibrotic therapeutic target through regulating Gli3 in vivo and in vitro.

INTRODUCTION AND OBJECTIVES: Liver fibrosis is a major characteristic of most chronic liver diseases which leads to accumulation of extracellular matrix (ECM) proteins. Hedgehog (Hh) pathway activated by Gli genes participated in the pathogenesis of liver fibrosis. However, the regulatory role of miR-125b in liver fibrosis via targeting Gli genes remains unknown. MATERIALS AND METHODS: RT-qPCR and western blot were employed to the expression levels of mRNA and protein, respectively. The fibrosis level of liver tissue was determined by Masson's trichrome staining. The interaction between miR-125b and Gli3 was tested by luciferase reporter assay. In addition, LX2 cells were activated and CCl4-induced rat model was used in this study. RESULTS: miR-125b was significantly declined in serum samples of the clinical liver fibrosis patient, activated LX2 cells and the liver tissues of the CCl4-induced rat model. Furthermore, in cellular level, the alpha-smooth muscle actin (α-SMA) and Albumin expressions were ascending and descending in LX2 cells, respectively, with the decline of miR-125b. However, when transfecting with miR-125b mimic, the expressions of α-SMA and Albumin was reversed and Gli3 expression was notably repressed in LX2 cells. The target interaction between miR-125b and Gli3 was determined by dual-luciferase assays. It was further discovered that the changes of α-SMA, Albumin, and Gli3 were similar to the expression trend in LX2 cells with miR-125b mimic transfection. CONCLUSION: These results suggested that miR-125b might be protective against liver fibrosis via regulating Gli3 and it might be a promising target in the development of novel therapies to treat pathological fibrotic disorders.

Differentiation of the Chinese minority medicinal plant genus Berchemia spp. by evaluating three candidate barcodes.

The genus Berchemia comprises important Chinese plants with considerable medicinal value; however, these plants are often misidentified in the herbal medicinal market. To differentiate the various morphotypes of Berchemia species, a proficient method employing the screening of universal DNA barcodes was used in this work. Three candidate barcoding loci, namely, psbA-trnH, rbcL, and the second internal transcribed spacer (ITS2), were used to identify an effective DNA barcode that can differentiate the various Berchemia species. Additionally, PCR amplification, efficient sequencing, intra- and inter-specific divergences, and DNA barcoding gaps were employed to assess the ability of each barcode to identify these diverse Berchemia plants authentically; the species were differentiated using the Kimura two-parameter and maximum composite likelihood methods. Sequence data analysis showed that the ITS2 region was the most suitable candidate barcode and exhibited the highest interspecific divergence among the three DNA-barcoding sequences. A clear differentiation was observed at the species level, in which a maximum distance of 0.264 was exhibited between dissimilar species. Clustal analysis also demonstrated that ITS2 clearly differentiated the test species in a more effective manner than that with the two other barcodes at both the hybrid and variety levels. Results indicate that DNA barcoding is ideal for species-level identification of Berchemia and provides a foundation for further identification at the molecular level of other Rhamnaceae medicinal plants.

Rapid authentication of the precious herb saffron by loop-mediated isothermal amplification (LAMP) based on internal transcribed spacer 2 (ITS2) sequence.

Saffron is one of the most expensive species of Chinese herbs and has been subjected to various types of adulteration because of its high price and limited production. The present study introduces a loop-mediated isothermal amplification (LAMP) technique for the differentiation of saffron from its adulterants. This novel technique is sensitive, efficient and simple. Six specific LAMP primers were designed on the basis of the nucleotide sequence of the internal transcribed spacer 2 (ITS2) nuclear ribosomal DNA of Crocus sativus. All LAMP amplifications were performed successfully, and visual detection occurred within 60 min at isothermal conditions of 65 °C. The results indicated that the LAMP primers are accurate and highly specific for the discrimination of saffron from its adulterants. In particular, 10 fg of genomic DNA was determined to be the limit for template accuracy of LAMP in saffron. Thus, the proposed novel, simple, and sensitive LAMP assay is well suited for immediate on-site discrimination of herbal materials. Based on the study, a practical standard operating procedure (SOP) for utilizing the LAMP protocol for herbal authentication is provided.

Rapid Identification and Verification of Indirubin-Containing Medicinal Plants.

Indirubin, one of the key components of medicinal plants including Isatis tinctoria, Polygonum tinctorium, and Strobilanthes cusia, possesses great medicinal efficacy in the treatment of chronic myelocytic leukemia (CML). Due to misidentification and similar name, materials containing indirubin and their close relatives frequently fall prey to adulteration. In this study, we selected an internal transcribed spacer 2 (ITS2) for distinguishing these indirubin-containing species from five of their usual adulterants, after assessing identification efficiency of matK, rbcL, psbA-trnH, and ITS2 among these species. The results of genetic distances and neighbor-joining (NJ) phylogenetic tree indicated that ITS2 region is a powerful DNA barcode to accurately identify these indirubin-containing species and discriminate them from their adulterants. Additionally, high performance liquid chromatography (HPLC) was used to verify indirubin in different organs of the above species. The results showed that indirubin had been detected in the leaves of Is. tinctoria, P. tinctorium, S. cusia, and Indigo Naturalis (made from their mixture), but not in their roots, or in the leaves of their adulterants. Therefore, this study provides a novel and rapid method to identify and verify indirubin-containing medicinal plants for effective natural treatment of CML.