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Abstract Background Papillary thyroid cancer (PTC) is a malignant tumor that poses a serious threat to human health. LncRNA CASC9 serves as an oncogene in numerous tumors. The purpose of this study was to explore the mechanism of lncRNA CASC9 regulating doxorubicin (Dox) resistance in PTC. Methods The expression of CASC9, miR-28-3p and BCL-2 in PTC tissues or dox-resistant cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB). CCK-8, colony formation assay, flow cytometry and transwell assay were used to measure the semi-inhibitory concentration (IC50) of dox, cell proliferation, apoptosis and migration, respectively. Dual luciferase reporter gene assays were performed to verify the targeting relationship between miR-28-3p and CASC9 or BCL-2. Rescue experiments were applied to verify the mechanism of CASC9. Finally, the role of CASC9 was verified by xenograft modeling in vivo. Results We discovered that CASC9 was enhanced in PTC tissues, cells and Dox-resistant cells (BCPAP/Dox and K1/Dox). Furthermore, CASC9 inhibition markedly restrained the proliferation, migration and facilitated apoptosis of Dox cells. In vivo experiments also showed that silencing of CASC9 inhibited tumor growth. Meanwhile, knockdown of CASC9 sensitized PTC cells to Dox. CASC9 enhanced tumor progression by activating the PI3K/AKT signaling pathway. Furthermore, bioinformatics analysis identified miR-28-3p as a downstream target of CASC9. MiR-28-3p inhibitor reversed the impact of CASC9 knockdown in BCPAP/Dox and K1/Dox. Further studies showed that CASC9 positively regulated BCL-2 expression through miR-28-3p. miR-28-3p weakened Dox resistance, proliferation, migration and accelerated apoptosis of PTC cells via BCL-2. Conclusion CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway.

Abstract Silica fiber under high pressure increases the risk of fiber breakage or permanent deformation, which may cause sensor failure due to mechanical strength limitations. High pressure can also induce birefringence in optical fiber. In this study, we present a simple design and low-cost high pressure sensor using polymer optical fiber (POF) based on the intensity-variation technique. A side-coupling mechanism in the sensor structure is adopted, which varies the intensity with applied pressure. Two POFs are twisted together to create a sensing region where the light is launched in the first fiber and measurement is taken from the second fiber. In sensing phenomena, cladding mode frustrated total internal reflection occurs when pressure increases. Silicone gel is used in the pressure chamber for sealing and preventing leakage. The sensor structure is able to detect high pressure in the MPa range, where we tested up to 4 MPa. For higher sensitivity, twisted and bend structure is analyzed, and sensitivity is achieved at about 432.21 nW/MPa. However, twisted helical structure is adopted to enhance sensing range which is about 50 cm. The proposed high-pressure sensor structure is easier to fabricate and has high stability because it doesn’t require any destructive method as compared to other conventional methods.

Background Leptomeningeal collateral status is a major determinant of outcomes in patients with acute ischemic stroke; however, the factors that determine collateral status are not well understood. We conducted a comprehensive systematic review and meta‐analysis to identify determinants associated with collateral status in patients with anterior circulation infarction. Methods and Results The PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for studies that reported the determinants of leptomeningeal collateral status in acute ischemic stroke between January 2000 and June 2023. A random‐effects meta‐analysis model was used to pool the determinants of leptomeningeal collateral status. Eighty‐one studies with 17 366 patients met the inclusion criteria. We analyzed 31 potential risk factors, and the results indicated that worse leptomeningeal collateral status was significantly associated with older age (weighted mean difference, 1.22 [95% CI, 0.69 to 1.76]), male sex (odds ratio [OR], 1.12 [95% CI, 1.02 to 1.23]), hypertension (OR, 1.27 [95% CI, 1.15 to 1.40]), diabetes (OR, 1.21 [95% CI, 1.10 to 1.33]), atrial fibrillation (OR, 1.26 [95% CI, 1.09 to 1.46]), cardioembolic stroke (OR, 1.27 [95% CI, 1.04 to 1.55]), internal carotid artery occlusion (OR, 1.84 [95% CI, 1.50 to 2.25]), and higher admission blood glucose (weighted mean difference, 8.74 [95% CI, 2.52 to 18.51]). Conclusions Hypertension and diabetes could be modifiable risk factors associated with leptomeningeal collateral status. Older age and male sex could be nonmodified risk factors. Further high‐quality therapeutic studies focusing on controlling risk factors are needed to support our findings.

BackgroundObsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD.MethodsPubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm.ResultsA total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis.ConclusionOCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

To improve the processing efficiency and extend the tuning range of 3D isotropic fabrication, we apply the simultaneous spatiotemporal focusing (SSTF) technique to a high-repetition-rate femtosecond (fs) fiber laser system. In the SSTF scheme, we propose a pulse compensation scheme for the fiber laser with a narrow spectral bandwidth by building an extra-cavity pulse stretcher. We further demonstrate truly 3D isotropic microfabrication in photosensitive glass with a tunable resolution ranging from 8 µm to 22 µm using the SSTF of fs laser pulses. Moreover, we systematically investigate the influences of pulse energy, writing speed, processing depth, and spherical aberration on the fabrication resolution. As a proof-of-concept demonstration, the SSTF scheme was further employed for the fs laser-assisted etching of complicated glass microfluidic structures with 3D uniform sizes. The developed technique can be extended to many applications such as advanced photonics, 3D biomimetic printing, micro-electromechanical systems, and lab-on-a-chips.

CAR-T cell therapy, a novel immunotherapy, has made significant breakthroughs in clinical practice, particularly in treating B-cell-associated leukemia and lymphoma. However, it still faces challenges such as poor persistence, limited proliferation capacity, high manufacturing costs, and suboptimal efficacy. CRISPR/Cas system, an efficient and simple method for precise gene editing, offers new possibilities for optimizing CAR-T cells. It can increase the function of CAR-T cells and reduce manufacturing costs. The combination of CRISPR/Cas9 technology and CAR-T cell therapy may promote the development of this therapy and provide more effective and personalized treatment for cancer patients. Meanwhile, the safety issues surrounding the application of this technology in CAR-T cells require further research and evaluation. Future research should focus on improving the accuracy and safety of CRISPR/Cas9 technology to facilitate the better development and application of CAR-T cell therapy. This review focuses on the application of CRISPR/Cas9 technology in CAR-T cell therapy, including eliminating the inhibitory effect of immune checkpoints, enhancing the ability of CAR-T cells to resist exhaustion, assisting in the construction of universal CAR-T cells, reducing the manufacturing costs of CAR-T cells, and the security problems faced. The objective is to show the revolutionary role of CRISPR/Cas9 technology in CAR-T cell therapy for researchers.

Identification and manipulation of cellular energy regulation mechanisms may be a strategy to increase productivity in photosynthetic organisms. This work tests the hypothesis that polyphosphate synthesis and degradation play a role in energy management by storing or dissipating energy in the form of ATP. A polyphosphate kinase (ppk) knock-out strain unable to synthesize polyphosphate was generated in the cyanobacterium Synechocystis sp. PCC 6803. This mutant strain demonstrated higher ATP levels and faster growth than the wildtype strain in high-carbon conditions and had a growth defect under multiple stress conditions. In a strain that combined ppk deletion with heterologous expression of ethylene-forming enzyme, higher ethylene productivity was observed than in the wildtype background. These results support the role of polyphosphate synthesis and degradation as an energy regulation mechanism and suggest that such mechanisms may be effective targets in biocontainment design.

Herein, an on‐chip 8‐channel thin‐film lithium niobate (TFLN) arrayed waveguide grating (AWG) is designed and the device is fabricated using photolithography‐assisted chemo‐mechanical etching technique. The transmission of the fabricated TFLN AWG near the central wavelength of 1550 nm is experimentally measured. An on‐chip loss as low as 3.32 dB, a single‐channel bandwidth of 1.6 nm, and a total‐channel bandwidth of 12.8 nm are obtained. The cross talk between adjacent channels is measured to be below −3.83 dB within the wavelength range from 1543 to 1558 nm, and the cross talk between nonadjacent channels is below −15 dB.

Abstract As a result of global warming, plants are subjected to ever-increasing abiotic stresses including heat and drought. Drought stress frequently co-occurs with heat stress as a result of water evaporation. These stressors have adverse effects on crop production, which in turn affects human food security. Rice is a major food resource grown widely in crop-producing regions throughout the world. However, increasingly common heat and drought stresses in growth regions can have negative impacts on seedling morphogenesis, reproductive organ establishment, overall yield, and quality. This review centers on responses to heat and drought stress in rice. Current knowledge of molecular regulation mechanisms is summarized. We focus on approaches to cope with heat and drought stress, both at the genetic level and from an agricultural practice perspective. This review establishes a basis for improving rice stress tolerance, grain quality, and yield for human benefit.

Abstract Background Statins have long been extensively prescribed as effective lipid-lowering agents, but statins have also been recognized as novel immunomodulators in recent years. This study was designed to investigate the immunomodulatory effects of atorvastatin on lupus-prone MRL/lpr mice. Methods A total of 30 8-week-old female MRL/lpr mice were randomly divided into three groups and orally administered vehicle, atorvastatin orhydroxychloroquine sulfate for 11 weeks. In vivo, the effects of atorvastatin on the survival rate, renal function and spleen index in MRL/lpr mice were examined. Ex vivo, splenic B-cell proliferation was assessed by a Cell Counting Kit-8. Results Oral atorvastatin failed to prolong survival time, or reduce the levels of proteinuria, or serum anti-dsDNA antibody and complement proteins (C3, C4). Histologically, no significant improvement by atorvastatin was observed in the pathological manifestations of renal damage, while hydroxychloroquine sulfate significantly improved glomerular injury. Ex vivo, atorvastatin suppressed the proliferation of splenic B lymphocytes. Conclusion Oral atorvastatin monotherapy had no therapeutic effects on MRL/lpr mice, whereas atorvastatin inhibited splenic B-cell proliferation in vitro, suggesting that atorvastatin has a potential therapeutic effect on systemic lupus erythematosus.

Excess phosphorus (P) in wastewater effluent poses a serious threat to aquatic ecosystems and can spur harmful algal blooms. Revolving algal biofilm (RAB) systems are an emerging technology to recover P from wastewater before discharge into aquatic ecosystems. In RAB systems, a community of microalgae take up and store wastewater P as polyphosphate as they grow in a partially submerged revolving biofilm, which may then be harvested and dried for use as fertilizer in lieu of mined phosphate rock. In this work, we isolated and characterized a total of 101 microalgae strains from active RAB systems across the US Midwest, including 82 green algae, 9 diatoms, and 10 cyanobacteria. Strains were identified by microscopy and 16S/18S ribosomal DNA sequencing, cryopreserved, and screened for elevated P content (as polyphosphate). Seven isolated strains possessed at least 50% more polyphosphate by cell dry weight than a microalgae consortium from a RAB system, with the top strain accumulating nearly threefold more polyphosphate. These top P-hyperaccumulating strains include the green alga Chlamydomonas pulvinata TCF-48 g and the diatoms Eolimna minima TCF-3d and Craticula molestiformis TCF-8d, possessing 11.4, 12.7, and 14.0% polyphosphate by cell dry weight, respectively. As a preliminary test of strain application for recovering P, Chlamydomonas pulvinata TCF-48 g was reinoculated into a bench-scale RAB system containing Bold basal medium. The strain successfully recolonized the system and recovered twofold more P from the medium than a microalgae consortium from a RAB system treating municipal wastewater. These isolated P-hyperaccumulating microalgae may have broad applications in resource recovery from various waste streams, including improving P removal from wastewater.

Abstract Problem background Early detection of acute ischemic stroke (AIS) may provide patients with benefits against harmful health and financial impacts. The use of non-contrast computed tomography images for early detect of the infarct remains controversial. Materials & methods Here, we used the UCATR algorithm to extract the pixel values of the infarct and the corresponding contralateral healthy area as the control surface in each NCCT slice for the whole brain. Magnetic resonance imaging results were used to verify both areas. We found significant pathological changes in the infarct compared with the corresponding contralateral healthy area in each NCCT slice. Attained results Our approach validated that NCCT can be used to detect the lesion area in the early stage of AIS. Conclusions With obvious advantages such as saving time and the ability to quantify the infarct volume, this approach could help more patients survive the fatal and irreversible pathological process of AIS and improve their quality of life after AIS treatment.

Photosynthetic productivity is limited by low energy conversion efficiency in naturally evolved photosynthetic organisms, via multiple mechanisms that are not fully understood. Here we show evidence that extends recent findings that cyanobacteria use “futile” cycles in the synthesis and degradation of carbon compounds to dissipate ATP. Reduction of the glycogen cycle or the sucrose cycle in the model cyanobacterium Synechocystis 6803 led to redirection of cellular energy toward faster growth under simulated outdoor light conditions in photobioreactors that was accompanied by higher energy charge [concentration ratio of ATP/(ATP + ADP)]. Such manipulation of energy metabolism may have potential in engineering microalgal chassis cells to increase productivity of biomass or target metabolites.

In recent years, the explosion of big data has presented unparalleled opportunities for the advancement of machine learning (ML). However, the vast size and sensitive nature of these datasets present significant challenges in terms of privacy and security. Federated Learning has emerged as a promising solution that enables a group of participants to train ML models without compromising the confidentiality of their raw data. Despite its potential, traditional federated learning faces challenges such as the absence of participant incentives and audit mechanisms. Furthermore, these challenges become more significant when dealing with the scale and diversity of big data, making efficient and reliable federated learning a complex task. These limitations may compromise model quality due to potential malicious nodes. To address the above issues, this paper proposes a BlockChain-based Decentralized Federated Learning (BCD-FL) model. In BCD-FL, we design a smart contract approach based on the reverse auction-based incentive mechanism and a reputation mechanism to promote the participation of reliable and high-quality data owners. Theoretical analysis shows that the BCD-FL model satisfies several desirable properties, such as individual rationality, computational efficiency, budget balance, and truthfulness. In addition, experimental results also show that the proposed model enables more efficient federated learning and provides some level of protection against malicious nodes. Therefore, the BCD-FL model presents a potential solution to the challenges in federated learning and opens up new possibilities for achieving efficient large-scale machine learning.

Muntjac deer underwent rapid species radiation and dramatic chromosome fusions within a short period of time. Here the authors reveal that repeat sequences likely mediated illegitimate recombination to result in chromosome fusions and that 3D chromatin architecture around fusion sites have no significant change, while significant interactions across fusion sites were gradually established after speciation.

Abstract Background Cadmium (Cd) is a toxic heavy metal that is harmful to the environment and human health. Cd pollution threatens the cultivation of rice (Oryza sativa L.) in many countries. Improving rice performance under Cd stress could potentially improve rice productivity. Results In this study, 9 growth traits of 188 different cultivated rice accessions under normal and Cd stress conditions were found to be highly variable during the seedling stage. Based on ~3.3 million single nucleotide polymorphisms (SNPs), 119 Cd-mediated growth response (CGR) quantitative trait loci (QTL) were identified by a genome-wide association study (GWAS), 55 of which have been validated by previously reported QTL and 64 were new CGR loci. Combined with the data from the GWAS, transcriptome analysis, gene annotations from the gene ontology (GO) Slim database, and annotations and functions of homologous genes, 148 CGR candidate genes were obtained. Additionally, several reported genes have been found to play certain roles in CGRs. Seven Cd-related cloned genes were found among the CGR genes. Natural elite haplotypes/alleles in these genes that increased Cd tolerance were identified by a haplotype analysis of a diverse mini core collection. More importantly, this study was the first to uncover the natural variations of 5 GST genes that play important roles in CGRs. Conclusion The exploration of Cd-resistant rice germplasm resources and the identification of elite natural variations related to Cd-resistance will help improve the tolerance of current major rice varieties to Cd, as well as provide raw materials and new genes for breeding Cd-resistant varieties.

The metabolic pathways used by microbes to degrade guanidine or mitigate its toxicity remain unclear. Here, the authors report a guanidine degrading enzyme that controls genomic stability of ethylene producing cyanobacterial strains.

The Chinese Plan has provided an important model for the global fight against COVID-19 since its outbreak. The present study describes the structural characteristics of China's COVID-19 patent cooperation network at the province, city, and applicant levels by using social network analysis based on data from the Incopat global patent database since 2020, which helps to clarify the current technology accumulation in this field in China, and provide patent information support for the scientific efforts to fight against COVID-19. The findings are as follows: First, the inter-regional cooperation level in China's COVID-19 patent cooperation network shows a decreasing trend from eastern to central to western regions. At the inter-applicant cooperation level, kinship-based cooperation is the strongest, business-based cooperation has the widest scope, while proximity-based cooperation exists throughout these two main models of cooperation. Second, coastal provinces and cities occupy a core position in the network, and play an important role in utilizing structural holes and bridging. Patent applicants with high centrality are mostly firms. Research institutes and universities mainly play the role of bridges. Third and lastly, there is no large number of cliques at the province and city levels. However, there is a tendency for cliques to develop at the applicant level. Hence, actions are needed to prevent the development of information barriers.

In this study, superhydrophobic ZnO/Polytetrafluoroethylene (ZnO/PTFE) films with water droplet contact angles (CA) observed as high as 165° and water droplet sliding angles of (SA) E. coli, the cell viability count of the ZnO/PTFE sample (3.5 log reduction, 99.96%) was conspicuously lower than that of the ZnO/HDTMS sample (1.2 log reduction, 93.87%) under 1 h illumination of UV light, which showed that the ZnO/PTFE sample has a better photocatalytic property than the ZnO/ HDTMS films. The ZnO/PTFE films also showed good mechanical robustness, which is an important consideration in their widespread real-world adoption.

Abstract Anxiety and depression are common mental illness in stroke caregivers, resulting in significant stress to the emotion health of caregivers. Caregivers’ emotion can seriously affect the recovery rate of stroke patient, therefore, how to control and affect the caregivers’ anxiety and depression is of great importance. Here three multiple centers observation and validation study were performed to screen out the risk factors for development of anxiety and depression in main family caregiver, and the effect of anxiety and depression of family caregivers on 6-month mortality of patients with moderate-severe stroke. The severity of the stroke, the duration of care time and the medical payment associated with increased risk of anxiety and depression. Anxiety and depression of main family caregivers are associated with increased risk 6-month mortality of patients with moderate-severe stroke. Therefore, the support provided to the family caregivers might have positive effect on prognosis of the patients with stroke.

BackgroundCognitive behavioral therapy (CBT) is a first-line psychotherapeutic treatment that has been recommended for psychiatric disorders. Prior neuroimaging studies have provided preliminary evidence suggesting that CBT can have an impact on the activity of brain regions and functional integration between regions. However, the results are far from conclusive. The present article aimed to detect characteristic changes in brain activation following CBT across psychiatric disorders.MethodWeb of Science, Cochrane Library, Scopus, and PubMed databases were searched to identify whole-brain functional neuroimaging studies of CBT through 4 August 2021. To be included in the meta-analysis, studies were required to examine functional activation changes between pre-and post-CBT. The included studies were then divided into subgroups according to different task paradigms. Then, an activation likelihood estimation algorithm (ALE) was performed in the different meta-analyses to identify whether brain regions showed consistent effects. Finally, brain regions identified from the meta-analysis were categorized into eight functional networks according to the spatial correlation values between independent components and the template.ResultsIn total, 13 studies met inclusion criteria. Three different meta-analyses were performed separately for total tasks, emotion tasks, and cognition tasks. In the total task ALE meta-analysis, the left precuneus was found to have decreased activation. For the cognition task ALE meta-analysis, left anterior cingulate (ACC) and left middle frontal gyrus (MFG) were found to have decreased activation following CBT. However, the emotion task ALE meta-analysis did not find any specific brain regions showing consistent effects. A review of included studies revealed default mode network (DMN), executive control network (ECN), and salience network (SN) were the most relevant among the eight functional networks.ConclusionThe results revealed that the altered activation in the prefrontal cortex and precuneus were key regions related to the effects of CBT. Therefore, CBT may modulate the neural circuitry of emotion regulation. This finding provides recommendations for the rapidly developing literature.

Abstract In mammalian cells, long noncoding RNAs (lncRNAs) form complexes with proteins to execute various biological functions such as gene transcription, RNA processing and other signaling activities. However, methods to track endogenous lncRNA dynamics in live cells and screen for lncRNA interacting proteins are limited. Here, we report the development of CERTIS (CRISPR-mediated Endogenous lncRNA Tracking and Immunoprecipitation System) to visualize and isolate endogenous lncRNA, by precisely inserting a 24-repeat MS2 tag into the distal end of lncRNA locus through the CRISPR/Cas9 technology. In this study, we show that CERTIS effectively labeled the paraspeckle lncRNA NEAT1 without disturbing its physiological properties and could monitor the endogenous expression variation of NEAT1. In addition, CERTIS displayed superior performance on both short- and long-term tracking of NEAT1 dynamics in live cells. We found that NEAT1 and paraspeckles were sensitive to topoisomerase I specific inhibitors. Moreover, RNA Immunoprecipitation (RIP) of the MS2-tagged NEAT1 lncRNA successfully revealed several new protein components of paraspeckle. Our results support CERTIS as a tool suitable to track both spatial and temporal lncRNA regulation in live cells as well as study the lncRNA-protein interactomes.

Abstract Background Cyanobacteria can be metabolically engineered to convert CO2 to fuels and chemicals such as ethylene. A major challenge in such efforts is to optimize carbon fixation and partition towards target molecules. Results The efe gene encoding an ethylene-forming enzyme was introduced into a strain of the cyanobacterium Synechocystis PCC 6803 with increased phosphoenolpyruvate carboxylase (PEPc) levels. The resulting engineered strain (CD-P) showed significantly increased ethylene production (10.5 ± 3.1 µg mL−1 OD−1 day−1) compared to the control strain (6.4 ± 1.4 µg mL−1 OD−1 day−1). Interestingly, extra copies of the native pepc or the heterologous expression of PEPc from the cyanobacterium Synechococcus PCC 7002 (Synechococcus) in the CD-P, increased ethylene production (19.2 ± 1.3 and 18.3 ± 3.3 µg mL−1 OD−1 day−1, respectively) when the cells were treated with the acetyl-CoA carboxylase inhibitor, cycloxydim. A heterologous expression of phosphoenolpyruvate synthase (PPSA) from Synechococcus in the CD-P also increased ethylene production (16.77 ± 4.48 µg mL−1 OD−1 day−1) showing differences in the regulation of the native and the PPSA from Synechococcus in Synechocystis. Conclusions This work demonstrates that genetic rewiring of cyanobacterial central carbon metabolism can enhance carbon supply to the TCA cycle and thereby further increase ethylene production.

Algae (including eukaryotic microalgae and cyanobacteria) have been genetically engineered to convert light and carbon dioxide to many industrially and commercially relevant chemicals including biofuels, materials, and nutritional products. At industrial scale, genetically engineered algae may be cultivated outdoors in open ponds or in closed photobioreactors. In either case, industry would need to address a potential risk of the release of the engineered algae into the natural environment, resulting in potential negative impacts to the environment. Genetic biocontainment strategies are therefore under development to reduce the probability that these engineered bacteria can survive outside of the laboratory or industrial setting. These include active strategies that aim to kill the escaped cells by expression of toxic proteins, and passive strategies that use knockouts of native genes to reduce fitness outside of the controlled environment of labs and industrial cultivation systems. Several biocontainment strategies have demonstrated escape frequencies below detection limits. However, they have typically done so in carefully controlled experiments which may fail to capture mechanisms of escape that may arise in the more complex natural environment. The selection of biocontainment strategies that can effectively kill cells outside the lab, while maintaining maximum productivity inside the lab and without the need for relatively expensive chemicals will benefit from further attention.

We propose a hybrid laser microfabrication approach for the manufacture of three-dimensional (3D) optofluidic spot-size converters in fused silica glass by a combination of femtosecond (fs) laser microfabrication and carbon dioxide laser irradiation. Spatially shaped fs laser-assisted chemical etching was first performed to form 3D hollow microchannels in glass, which were composed of embedded straight channels, tapered channels, and vertical channels connected to the glass surface. Then, carbon dioxide laser-induced thermal reflow was carried out for the internal polishing of the whole microchannels and sealing parts of the vertical channels. Finally, 3D optofluidic spot-size converters (SSC) were formed by filling a liquid-core waveguide solution into laser-polished microchannels. With a fabricated SSC structure, the mode spot size of the optofluidic waveguide was expanded from ~8 μm to ~23 μm with a conversion efficiency of ~84.1%. Further measurement of the waveguide-to-waveguide coupling devices in the glass showed that the total insertion loss of two symmetric SSC structures through two ~50 μm-diameter coupling ports was ~6.73 dB at 1310 nm, which was only about half that of non-SSC structures with diameters of ~9 μm at the same coupling distance. The proposed approach holds great potential for developing novel 3D fluid-based photonic devices for mode conversion, optical manipulation, and lab-on-a-chip sensing.

The development of pressure sensors of high sensitivity and stable robustness over a broad range is indispensable for the future progress of electronic skin applicable to the detection of normal and shear pressures of various dynamic human motions. Herein, we present a flexible capacitive tactile sensing array that incorporates a porous dielectric layer with micro-patterned structures on the surface to enable the sensitive detection of normal and shear pressures. The proposed sensing array showed great pressure-sensing performance in the experiments, with a broad sensing range from several kPa to 150 kPa of normal pressure and 20 kPa of shear pressure. Sensitivities of 0.54%/kPa at 10 kPa and below, 0.45%/kPa between 10 kPa and 80 kPa, and 0.12%/kPa at 80 kPa and above were achieved for normal pressures. Meanwhile, for shear pressures, sensitivities up to 1.14%/kPa and 1.08%/kPa in x and y directions, respectively, and below 10 kPa, 0.73%/kPa, and 0.75%/kPa under shear pressure over 10 kPa were also validated. The performance of the finger-attached sensing array was also demonstrated, demonstrating which was a potential electronic skin to use in all kinds of wearable devices, including prosthetic hands, surgical robots, and other pressure monitoring systems.

Exploring the path and mechanism of marketization level in the effect of foreign direct investment (FDI) on carbon emission performance will help to maximize the stimulation effect of foreign investment on green and low-carbon development. This study used the panel data of 11 provinces and cities in the Yangtze River Economic Belt from 2008 to 2016. A panel threshold model is constructed to explore the non-linear relationship between FDI and carbon emissions performance from the perspective of marketization level. The main conclusions are as follows: First, from the perspective of marketization level, a significant double threshold effect exists between foreign participation and carbon emission intensity, with threshold values of 4.4701 and 9.2516 respectively. Second, as the marketization level increases, the technology spillover effect of FDI increases, and the stimulation effect of foreign participation on carbon intensity decreases significantly, but it does not inhibit carbon intensity, indicating that the overall benefits brought by FDI technology spillovers are still insufficient to offset pollution caused by foreign investment. Third, the eastern region of the Yangtze River Economic Belt has crossed the second threshold. In the central and western regions, the marketization process is relatively slow except for Chongqing, and the regions are still firmly stuck between the first and second thresholds. In response to the conclusions of the empirical research, relevant policy suggestions are put forward from three dimensions, namely, the strategy of introducing foreign investment, construction of the marketization system, and environmental regulation, to achieve low-carbon and green development in the Yangtze River Economic Belt.

Abstract Background Small nucleolar RNA host gene 3 (Snhg3) is a long non-coding RNA (lncRNA) that was shown to participate in the tumorigenesis of certain cancers. However, little is known about its role in embryonic stem cells (ESCs). Methods Here, we investigated the role of Snhg3 in mouse ESCs (mESCs) through both loss-of-function (knockdown) and gain-of-function (overexpression) approaches. Alkaline phosphatase staining, secondary colony formation, propidium iodide staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to access self-renewal capacity, whereas immunofluorescence, qRT-PCR, and embryoid body formation were performed to examine pluripotency. In addition, the effect of Snhg3 on mouse embryonic development was determined based on the morphological changes, blastocyst rate, and altered pluripotency marker (Nanog, Oct4) expression. Moreover, the relationship between Snhg3 and key pluripotency factors was evaluated by chromatin immunoprecipitation qPCR, qRT-PCR, subcellular fractionation, and RNA immunoprecipitation. Finally, RNA pull-down and mass spectrometry were applied to explore the potential interacting proteins of Snhg3 in mESCs. Results We demonstrated that Snhg3 is essential for self-renewal and pluripotency maintenance in mESCs. In addition, Snhg3 knockdown disrupted mouse early embryo development. Mechanistically, Snhg3 formed a positive feedback network with Nanog and Oct4, and 126 Snhg3-interacting proteins were identified in mESCs. Conclusions Snhg3 is essential for mESC self-renewal and pluripotency, as well as mouse early embryo development.

Background: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. Results: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. Conclusions: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal–striatal network, which distinguishes OCD from washing OCD.

We report the fabrication and optical characterization of Yb3+-doped waveguide amplifiers (YDWA) on the thin film lithium niobate fabricated by photolithography assisted chemo-mechanical etching. The fabricated Yb3+-doped lithium niobate waveguides demonstrates low propagation loss of 0.13 dB/cm at 1030 nm and 0.1 dB/cm at 1060 nm. The internal net gain of 5 dB at 1030 nm and 8 dB at 1060 nm are measured on a 4.0 cm long waveguide pumped by 976 nm laser diodes, indicating the gain per unit length of 1.25 dB/cm at 1030 nm and 2 dB/cm at 1060 nm, respectively. The integrated Yb3+-doped lithium niobate waveguide amplifiers will benefit the development of a powerful gain platform and are expected to contribute to the high-density integration of thin film lithium niobate based photonic chip.

Abstract Background Hirsutella Pat genus, the asexual morphs of the Ophiocordyceps Sung, is globally distributed entomopathogenic fungi, which infect a variety of arthropods, mites and nematodes. The fungal species also have shown potential application in the field of biological control, bio-medicine and food development. Although these fungi are synonymized under Ophiocordyceps, formal taxonomic assignments remain necessary for classification of species in Hirsutella. However, due to the heterogeneity and complexity of Hirsutella genus, more detailed taxonomic and phylogenetic analyses are required to address the following subjects: (1) the relationships between the phialide morphological characteristics and phylogenetic information of Hirsutella with asexual morphs, (2) the origin and evolution of the phialide structure, and (3) host specificity and fungal pathogenicity. Results Five typical phialide structures are summarized, in which the variation in phialide characteristics overlaps well with phylogenetic information. A new member of the special twisted neck clade in the Hirsutella-like group, Ophiocordyceps retorta, was reported based on these analyses. The molecular clock calibration analysis based on one fossil record revealed that Hirsutella (asexual morph) species originated from a common ancestor approximately 102 million years ago (Mya) (Early Cretaceous, Lower Albian) and then resolved into two major lineages. One lineage was typically phialidic, which was a larger shape, including H. guyana, H. nodulosa and H. sinensis clades (86.9 Mya, 95% highest posterior density (HPD): 69.1–101.4 Mya). Another main lineage of the phialides was more diversified and smaller than the former, which included H. citriformis and H. thompsonii clades (71.9 Mya, 95% HPD: 41.8–99.6 Mya). Conclusions Our results showed that certain phialide characteristics of Hirsutella were phylogenetically informative for two groups of taxa. The differentiation of the phialides structures in the major clades demonstrated a clear evolutionary path of Hirsutella (asexual morph) species, which exhibited two trends depending on the host size. Fungi in one of the groups displayed elongated conidiogenous cells with increased complexity of auxiliary structures from the mycelia. The species in another group reduced the volume of phialides and spores, which might be due to an energy-efficient strategy. These results suggested that a common origin allowed for diversification of given clades into separate niches. The distinct parallel evolutionary path combined with the specific phialides structure might result in the host specificity of Hirsutella (asexual morphs). A direct relationship between Hirsutella (asexual morphs) and the Cretaceous–Tertiary extinction was not found, which suggested that the diversity of phialides is more likely to be caused by long-term environmental adaptation and evolution rather than dramatic extinction events. This evolutionary result might correspond to the background of important biological and geological events in the late Cretaceous occurring near the divergence times of Hirsutella (asexual morphs).

Summary: Understanding how living cells manage high-energy metabolites such as ATP and NADPH is essential for understanding energy transformations in the biosphere. Using light as the energy input, we find that energy charge (ratio of ATP over ADP+ATP) in the cyanobacterium Synechocystis sp. PCC 6803 varies in different growth stages, with a peak upon entry into the rapid growth phase, as well as a positive correlation with light intensity. In contrast, a mutant that can no longer synthesize the main carbon storage compound glycogen showed higher energy charge. The overflow of organic acids in this mutant under nitrogen depletion could also be triggered under high light in nitrogen-replete conditions, with an energy input level dependency. These findings suggest that energy charge in cyanobacteria is tightly linked to growth and carbon partition and that energy management is of key significance for their application as photosynthetic carbon dioxide-assimilating cell factories. : Cano et al. find that ATP levels in a cyanobacterium are dynamic in growth phases and respond to intracellular and environmental conditions. A glycogen mutant excretes organic acids and adjusts photosynthesis as alternative strategies to maintain energy homeostasis. Keywords: cyanobacteria, synechocystis, energy charge, glycogen, overflow metabolism, photosynthesis

Abstract The Hirsutella genus is very special asexually-reproducing pathogens of insects by reduced sporulation, host specificity and spores covered by a thick mucilage layer. However, the ecological function of conidial mucilage remains elusive. In this study, the possible ecological role of conidial mucilage from the entomopathogenic fungus Hirsutella satumaensis was functionally investigated through tolerance, adherence and insect bioassays involving aerial conidia (AC) and mucilage-free conidia (MFC). Measurements of hydrophobicity using microbial adhesion to hydrocarbons (MATH) indicated that mucilage is main contributor to the surface hydrophobicity of AC. When subjected in tolerance assays to extreme temperatures, high chemical pressure, extended exposure to ultraviolet radiation and cold stress, AC produced more colonies, exhibited higher conidiation and germination percentages than those of MFC. In adhesion assays, MFC displayed an approximately 40% reduction in adherence to locust, dragonfly cuticle and onion epidermis when washed with 0.05% Tween 20. Similarly, Galleria mellonella and Plutella xylostella larvae infected with mucilage-producing AC experienced a relatively higher mortality rate. Our findings suggest that mucilage is critical to the ecological adaptability of H. satumaensis, where it plays positive roles on maintenance of spore surface hydrophobicity, enhancement of spore resistance to extreme environments and strengthening of spore adhesion and host pathogenicity.

Abstract Background Most agronomic traits in rice are complex and polygenic. The identification of quantitative trait loci (QTL) for grain length is an important objective of rice genetic research and breeding programs. Results Herein, we identified 99 QTL for grain length by GWAS based on approximately 10 million single nucleotide polymorphisms from 504 cultivated rice accessions (Oryza sativa L.), 13 of which were validated by four linkage populations and 92 were new loci for grain length. We scanned the Ho (observed heterozygosity per locus) index of coupled-parents of crosses mapping the same QTL, based on linkage and association mapping, and identified two new genes for grain length. We named this approach as Ho-LAMap. A simulation study of six known genes showed that Ho-LAMap could mine genes rapidly across a wide range of experimental variables using deep-sequencing data. We used Ho-LAMap to clone a new gene, OsLG3, as a positive regulator of grain length, which could improve rice yield without influencing grain quality. Sequencing of the promoter region in 283 rice accessions from a wide geographic range identified four haplotypes that seem to be associated with grain length. Further analysis showed that OsLG3 alleles in the indica and japonica evolved independently from distinct ancestors and low nucleotide diversity of OsLG3 in indica indicated artificial selection. Phylogenetic analysis showed that OsLG3 might have much potential value for improvement of grain length in japonica breeding. Conclusions The results demonstrated that Ho-LAMap is a potential approach for gene discovery and OsLG3 is a promising gene to be utilized in genomic assisted breeding for rice cultivar improvement.

Low temperature is a major factor limiting productivity in rice. Here the authors show that theCTB4a gene confers cold tolerance to japonicavarieties adapted to cold habitats at the booting stage of development, and propose that CTB4a acts via an interaction with the beta subunit of ATP synthase.

We investigated 16 Japanese spotted fever cases that occurred in southeastern China during September–October 2015. Patients had fever, rash, eschar, and lymphadenopathy. We confirmed 9 diagnoses and obtained 2 isolates with high identity to Rickettsia japonica strain YH. R. japonica infection should be considered for febrile patients in China.

Photosynthesis uses solar energy to drive inorganic carbon (Ci) uptake, fixation, and biomass formation. In cyanobacteria, Ci uptake is assisted by carbon concentrating mechanisms (CCM), and CO2 fixation is catalyzed by RubisCO in the Calvin-Benson-Bassham (CBB) cycle. Understanding the regulation that governs CCM and CBB cycle activities in natural and engineered strains requires methods and parameters that quantify these activities. Here, we used membrane-inlet mass spectrometry (MIMS) to simultaneously quantify Ci concentrating and fixation processes in the cyanobacterium Synechocystis 6803. By comparing cultures acclimated to ambient air conditions to cultures transitioning to high Ci conditions, we show that acclimation to high Ci involves a concurrent decline of Ci uptake and fixation parameters. By varying light input, we show that both CCM and CBB reactions become energy limited under low light conditions. A strain over-expressing the gene for the CBB cycle enzyme fructose-bisphosphate aldolase showed higher CCM and carbon fixation capabilities, suggesting a regulatory link between CBB metabolites and CCM capacity. While the engineering of an ethanol production pathway had no effect on CCM or carbon fixation parameters, additional fructose-bisphosphate aldolase gene over-expression enhanced both activities while simultaneously increasing ethanol productivity. These observations show that MIMS can be a useful tool to study the extracellular Ci flux and how CBB metabolites regulate Ci uptake and fixation.

We demonstrate a microfluidic mixer of high mixing efficiency in fused silica substrate using femtosecond laser-induced wet etching and hydroxide-catalysis bonding method. The micromixer has a three-dimensional geometry, enabling efficient mixing based on Baker’s transformation principle. The cross-sectional area of the fabricated micromixer was 0.5 × 0.5 mm2, enabling significantly promotion of the throughput of the micromixer. The performance of the fabricated micromixers was evaluated by mixing up blue and yellow ink solutions with a flow rate as high as 6 mL/min.

Chronic pain usually results in persistent anxiety, which worsens the life quality of patients and complicates the treatment of pain. Hippocampus is one of the few brain regions in many mammalians species which harbors adult neural stem cells (NSCs), and plays a key role in the development and maintenance of chronic anxiety. Recent studies have suggested a potential involvement of hippocampal neurogenesis in modulating chronic pain. Whether and how hippocampal NSCs are involved in the pain-associated anxiety remains unclear. Here, we report that mice suffering persistent neuropathic pain showed a quick reduction of active NSCs in the ventral dentate gyrus (vDG), which was followed by the decrease of neurogenesis and appearance of anxiety. Wnt/β-catenin signaling, a key pathway in sustaining the active status of NSCs was suppressed in the vDG of mice suffering chronic pain. Depleting β-catenin by inducible Nestin-Cre significantly reduced the number of active NSCs and facilitated anxiety development, while expressing stabilized β-catenin amplified active NSCs and alleviated anxiety, indicating that Wnt activated NSCs is required for anxiety development under chronic pain. Treatment with Fluoxetine, the most widely used anxiolytic in clinic, significantly increased the proliferation of active NSCs and enhanced Wnt signaling. Interestingly, both β-catenin manipulation and Fluoxetine treatment had no significant effects on the pain thresholds. Therefore, our data demonstrated an anxiety-specific response and contribution of activated NSCs to chronic pain through Wnt/β-catenin signaling, which may be targeted for treating chronic pain- or other diseases-associated anxiety.

In order to find a proper method to study the flow and sound fields in an axial-flow check valve, the jetting noise at a nozzle is investigated with simulations and experiments. Based on optimization principle, the main channel of the valve body is numerically investigated and optimized twice. The results show that the resistance coefficient and the maximum noise of the valve are decreased by 0.37 and 23.8 dB, respectively, and the head and the tail of the valve plug are optimized when streamline design is employed on the main channel structure of the valve body.

Low temperature affects the rice plants at all stages of growth. It can cause severe seedling injury and male sterility resulting in severe yield losses. Using a mini core collection of 174 Chinese rice accessions and 273 SSR markers we investigated cold tolerance at the germination and booting stages, as well as the underlying genetic bases, by association mapping. Two distinct populations, corresponding to subspecies indica and japonica showed evident differences in cold tolerance and its genetic basis. Both subspecies were sensitive to cold stress at both growth stages. However, japonica was more tolerant than indica at all stages as measured by seedling survival and seed setting. There was a low correlation in cold tolerance between the germination and booting stages. Fifty one quantitative trait loci (QTLs) for cold tolerance were dispersed across all 12 chromosomes; 22 detected at the germination stage and 33 at the booting stage. Eight QTLs were identified by at least two of four measures. About 46% of the QTLs represented new loci. The only QTL shared between indica and japonica for the same measure was qLTSSvR6-2 for SSvR. This implied a complicated mechanism of old tolerance between the two subspecies. According to the relative genotypic effect (RGE) of each genotype for each QTL, we detected 18 positive genotypes and 21 negative genotypes in indica, and 19 positive genotypes and 24 negative genotypes in japonica. In general, the negative effects were much stronger than the positive effects in both subspecies. Markers for QTL with positive effects in one subspecies were shown to be effective for selection of cold tolerance in that subspecies, but not in the other subspecies. QTL with strong negative effects on cold tolerance should be avoided during MAS breeding so as to not cancel the effect of favorable QTL at other loci.

We report here the sequencing and analysis of the genome of the purple non-sulfur photosynthetic bacterium Rubrivivax gelatinosus CBS. This microbe is a model for studies of its carboxydotrophic life style under anaerobic condition, based on its ability to utilize carbon monoxide (CO) as the sole carbon substrate and water as the electron acceptor, yielding CO2 and H2 as the end products. The CO-oxidation reaction is known to be catalyzed by two enzyme complexes, the CO dehydrogenase and hydrogenase. As expected, analysis of the genome of Rx. gelatinosus CBS reveals the presence of genes encoding both enzyme complexes. The CO-oxidation reaction is CO-inducible, which is consistent with the presence of two putative CO-sensing transcription factors in its genome. Genome analysis also reveals the presence of two additional hydrogenases, an uptake hydrogenase that liberates the electrons in H2 in support of cell growth, and a regulatory hydrogenase that senses H2 and relays the signal to a two-component system that ultimately controls synthesis of the uptake hydrogenase. The genome also contains two sets of hydrogenase maturation genes which are known to assemble the catalytic metallocluster of the hydrogenase NiFe active site. Collectively, the genome sequence and analysis information reveals the blueprint of an intricate network of signal transduction pathways and its underlying regulation that enables Rx. gelatinosus CBS to thrive on CO or H2 in support of cell growth.

The wireless sensor networks are usually deployed in various application-specific contexts, which can be treated as distributed databases with big data. The event-involved query responses can be obtained by issuing query requests to this kind of database. However, the constraints of the energy and delay have had a great impact on the operation of wireless sensor networks. How to design the query-involved network model and the corresponding query processing algorithms is extremely challenging. This work investigates query processing problem in resource-constrained wireless sensor networks with the two-tier architecture and multiple query agents, where the multiple nodes of query agents are configured in the networks and the corresponding source cluster-heads send collected events to only one optimum query agent. To reduce the energy consumption and shorten the delivery delay, an efficient query processing algorithm inspired by the swarm intelligence of ants is proposed, which takes advantage of the beneficial clustering and routing emerging in a hybrid self-organized way from the positive interaction of ants. The experimental results demonstrated that the proposed algorithm can deliver collected events to the optimum query agents efficiently. Not only is the energy cost reduced but also the delivery delay is shortened significantly when transmitting the named events to the appropriate query agents.