The Making of a Heterocyst in Cyanobacteria.

Heterocyst differentiation that occurs in some filamentous cyanobacteria, such as Anabaena sp. PCC 7120, provides a unique model for prokaryotic developmental biology. Heterocyst cells are formed in response to combined-nitrogen deprivation and possess a microoxic environment suitable for nitrogen fixation following extensive morphological and physiological reorganization. A filament of Anabaena is a true multicellular organism, as nitrogen and carbon sources are exchanged among different cells and cell types through septal junctions to ensure filament growth. Because heterocysts are terminally differentiated cells and unable to divide, their activity is an altruistic behavior dedicated to providing fixed nitrogen for neighboring vegetative cells. Heterocyst development is also a process of one-dimensional pattern formation, as heterocysts are semiregularly intercalated among vegetative cells. Morphogens form gradients along the filament and interact with each other in a fashion that fits well into the Turing model, a mathematical framework to explain biological pattern formation.

A conserved protein inhibitor brings under check the activity of RNase E in cyanobacteria.

The bacterial ribonuclease RNase E plays a key role in RNA metabolism. Yet, with a large substrate spectrum and poor substrate specificity, its activity must be well controlled under different conditions. Only a few regulators of RNase E are known, limiting our understanding on posttranscriptional regulatory mechanisms in bacteria. Here we show that, RebA, a protein universally present in cyanobacteria, interacts with RNase E in the cyanobacterium Anabaena PCC 7120. Distinct from those known regulators of RNase E, RebA interacts with the catalytic region of RNase E, and suppresses the cleavage activities of RNase E for all tested substrates. Consistent with the inhibitory function of RebA on RNase E, depletion of RNase E and overproduction of RebA caused formation of elongated cells, whereas the absence of RebA and overproduction of RNase E resulted in a shorter-cell phenotype. We further showed that the morphological changes caused by altered levels of RNase E or RebA are dependent on their physical interaction. The action of RebA represents a new mechanism, potentially conserved in cyanobacteria, for RNase E regulation. Our findings provide insights into the regulation and the function of RNase E, and demonstrate the importance of balanced RNA metabolism in bacteria.

A c-di-GMP binding effector controls cell size in a cyanobacterium.

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule. It is also a critical player in the regulation of cell size and cell behaviors such as cell aggregation and phototaxis in cyanobacteria, which constitute an important group of prokaryotes for their roles in the ecology and evolution of the Earth. However, c-di-GMP receptors have never been revealed in cyanobacteria. Here, we report the identification of a c-di-GMP receptor, CdgR, from the filamentous cyanobacterium Anabaena PCC 7120. Crystal structural analysis and genetic studies demonstrate that CdgR binds c-di-GMP at the dimer interface and this binding is required for the control of cell size in a c-di-GMP-dependent manner. Different functions of CdgR, in ligand binding and signal transmission, could be separated genetically, allowing us to dissect its molecular signaling functions. The presence of the apo-form of CdgR triggers cell size reduction, consistent with the similar effects observed with a decrease of c-di-GMP levels in cells. Furthermore, we found that CdgR exerts its function by interacting with a global transcription factor DevH, and this interaction was inhibited by c-di-GMP. The lethal effect triggered by conditional depletion of DevH or by the production of several point-mutant proteins of CdgR in cells indicates that this signaling pathway plays critical functions in Anabaena. Our studies revealed a mechanism of c-di-GMP signaling in the control of cell size, an important and complex trait for bacteria. CdgR is highly conserved in cyanobacteria, which will greatly expand our understanding of the roles of c-di-GMP signaling in these organisms.

A proteolytic pathway coordinates cell division and heterocyst differentiation in the cyanobacterium Anabaena sp. PCC 7120.

The filamentous, multicellular cyanobacterium Anabaena sp. PCC 7120 (Anabaena) is a prokaryotic model for the study of cell differentiation and cell-cell interactions. Upon combined-nitrogen deprivation, Anabaena forms a particular cell type, heterocyst, for aerobic nitrogen fixation. Heterocysts are semiregularly spaced among vegetative cells. Heterocyst differentiation is coupled to cell division, but the underlying mechanism remains unclear. This mechanism could be mediated by the putative protease HetF, which is a divisome component and is necessary for heterocyst differentiation. In this study, by suppressor screening, we identified PatU3, as a negative regulator acting downstream of HetF for cell division and heterocyst development. The inactivation of patU3 restored the capacity of cell division and heterocyst differentiation in the ΔhetF mutant, and overexpression of patU3 inhibited both processes in the wild-type background. We demonstrated that PatU3 was a specific substrate of the protease activity of HetF. Consequently, PatU3 accumulated in the hetF-deficient mutant, which was responsible for the resultant mutant phenotype. The cleavage site of PatU3 by HetF was mapped after the Arg117 residue, whose mutation made PatU3 resistant to HetF processing, and mimicked the effect of hetF deletion. Our results provided evidence that HetF regulated cell division and heterocyst differentiation by controlling the inhibitory effects of PatU3. This proteolytic pathway constituted a mechanism for the coordination between cell division and differentiation in a prokaryotic model used for studies on developmental biology and multicellularity.

Genotype diversity enhances invasion resistance of native plants via soil biotic feedbacks.

Although native species diversity is frequently reported to enhance invasion resistance, within-species diversity of native plants can also moderate invasions. While the positive diversity-invasion resistance relationship is often attributed to competition, indirect effects mediated through plant-soil feedbacks can also influence the relationship. We manipulated the genotypic diversity of an endemic species, Scirpus mariqueter, and evaluated the effects of abiotic versus biotic feedbacks on the performance of a global invader, Spartina alterniflora. We found that invader performance on live soils decreased non-additively with genotypic diversity of the native plant that trained the soils, but this reversed when soils were sterilized to eliminate feedbacks through soil biota. The influence of soil biota on the feedback was primarily associated with increased levels of microbial biomass and fungal diversity in soils trained by multiple-genotype populations. Our findings highlight the importance of plant-soil feedbacks mediating the positive relationship between genotypic diversity and invasion resistance.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

HetF defines a transition point from commitment to morphogenesis during heterocyst differentiation in the cyanobacterium Anabaena sp. PCC 7120.

The filamentous cyanobacterium Anabaena sp. PCC 7120 is able to form heterocysts for nitrogen fixation. Heterocyst differentiation is initiated by combined-nitrogen deprivation, followed by the commitment step during which the developmental process becomes irreversible. Mature heterocysts are terminally differentiated cells unable to divide, and cell division is required for heterocyst differentiation. Previously, we have shown that the HetF protease regulates cell division and heterocyst differentiation by cleaving PatU3, which is an inhibitor for both events. When hetF is required during the developmental program remains unknown. Here, by controlling the timing of hetF expression during heterocyst differentiation, we provide evidence that hetF is required just before the beginning of heterocyst morphogenesis. Consistent with this finding, transcriptome data show that most of the genes known to be involved in the early step (such as hetR and ntcA) or the commitment step (such as hetP and hetZ) of heterocyst development could be expressed in the ΔhetF mutant. In contrast, most of the genes involved in heterocyst morphogenesis and nitrogen fixation remain repressed in the mutant. These results indicated that in the absence of hetF, heterocyst differentiation is able to be initiated and proceeds to the stage just before heterocyst envelope formation.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Principles and methods of liquid metal actuators.

As a promising material, liquid metals (LMs) have gained considerable interest in the field of soft robotics due to their ability to move as designed routines or change their shape dramatically under external stimuli. Inspired by the science fiction film Terminator, tremendous efforts have been devoted to liquid robots with high compliance and intelligence. How to manipulate LM droplets is crucial to achieving this goal. Accordingly, this review is dedicated to presenting the principles driving LMs and summarizing the potential methods to develop LM actuators of high maneuverability. Moreover, the recent progress of LM robots based on these methods is overviewed. The challenges and prospects of implementing autonomous robots have been proposed.

Highly sensitive ammonia sensor based on a PMMA/PANI microwire structure.

In this paper, a highly sensitive ammonia (N H 3) sensor based on a polymethyl methacrylate/polyaniline (PMMA/PANI) microwire structure is designed and implemented. First, a micron-sized PMMA microwire was fabricated and connected with two tapered single-mode fibers to form a coupling structure; thus, the Mach-Zehnder (MZ) interference was successfully excited due to the good light conductivity of the PMMA. It was demonstrated that the coupling structure behaved with a high refractive index detection sensitivity of 3044 nm/RIU. To make it sensitive to N H 3, the PANI was selected to mix with PMMA and then formed a micron-level PMMA/PANI fiber. The experimental results showed that the PMMA/PANI fiber can selectively sense N H 3 with a high sensitivity of 65.3 pm/ppm. This proposed N H 3 sensor not only solves the problem of sensitive film shedding, but also possesses the advantages of good integration, high sensitivity, good selectivity, and short response time.

Identification and characterization of the Doublesex gene and its mRNA isoforms in the brine shrimp Artemia franciscana.

Doublesex (DSX) proteins are members of the Doublesex/mab-3-related (DMRT) protein family and play crucial roles in sex determination and differentiation among the animal kingdom. In the present study, we identified two Doublesex (Dsx)-like mRNA isoforms in the brine shrimp Artemia franciscana (Kellogg 1906), which are generated by the combination of alternative promoters, alternative splicing and alternative polyadenylation. The two transcripts exhibited sex-biased enrichment, which we termed AfrDsxM and AfrDsxF. They share a common region which encodes an identical N-terminal DNA-binding (DM) domain. RT-qPCR analyses showed that AfrDsxM is dominantly expressed in male Artemia while AfrDsxF is specifically expressed in females. Expression levels of both isoforms increased along with the developmental stages of their respective sexes. RNA interference with dsRNA showed that the knockdown of AfrDsxM in male larvae led to the appearance of female traits including an ovary-like structure in the original male reproductive system and an elevated expression of vitellogenin. However, silencing of AfrDsxF induced no clear phenotypic change in female Artemia. These results indicated that the male AfrDSXM may act as inhibiting regulator upon the default female developmental mode in Artemia. Furthermore, electrophoretic mobility shift assay analyses revealed that the unique DM domain of AfrDSXs can specifically bind to promoter segments of potential downstream target genes like AfrVtg. These data show that AfrDSXs play crucial roles in regulating sexual development in Artemia, and further provide insight into the evolution of sex determination/differentiation in sexual organisms.

Maintaining calcium homeostasis as a strategy to alleviate nephrotoxicity caused by evodiamine.

Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs.

The safety and short-term effect of mixed approach in laparoscopic right hemicolectomy for right colon cancer compared with middle approach: a retrospective study.

PURPOSE: To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. METHODS: A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. RESULTS: There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p < 0.001), intraoperative blood loss (73.8 ml vs 37.97 ml, p < 0.001) and postoperative drainage volume. There was no significant difference in the postoperative complications like postoperative anastomotic leakage, postoperative infection and postoperative intestinal obstruction. CONCLUSIONS: Compared with the middle approach, the mixed approach is a safe and advantageous way that can significantly shorten the operation time, reduce intraoperative bleeding and postoperative drainage volume, and does not prolong the length of hospital stay or increase the morbidity postoperative complications.

Transcriptional correlates of frequency-dependent brain functional activity associated with symptom severity in degenerative cervical myelopathy.

BACKGROUND: Neuroimaging techniques provide insights into the brain abnormalities secondary to degenerative cervical myelopathy (DCM) and their association with neurological deficits. However, the neural correlates underlying the discrepancy between symptom severity and the degree of spinal cord compression, as well as the transcriptional correlates of these cortical abnormalities, remain unknown in DCM patients. METHODS: In this cross-sectional study, which collected resting-state functional MRI (rs-fMRI) images and the Japanese Orthopedic Association (JOA) score, enrolled 104 participants (54 patients and 50 healthy controls). The frequency-dependent amplitude of low-frequency fluctuation (ALFF) was obtained for all participants. We investigated the ALFF differences between mild-symptom DCM patients and severe-symptom DCM patients while carefully matching the degree of compression between these two groups via both univariate comparison and searchlight classification for three frequency bands (e.g., Slow-4, Slow-5, and Full-band). Additionally, we identified genes associated with symptom severity in DCM patients by linking the spatial patterns of gene expression of Allen Human Brain Atlas and brain functional differences between mild symptom and severe symptom groups. RESULTS: (1) We found that the frequency-specific brain activities within the sensorimotor network (SMN), visual network (VN), and default mode network (DMN) were associated with the varying degrees of functional impairment in DCM patients; (2) the frequency-specific brain activity within the SMN correlated with the functional recovery in patients with DCM; (3) a spatial correlation between the brain-wide expression of genes involved in neuronal migration and the brain functional activities associated with symptom severity was identified in DCM patients. CONCLUSION: In conclusion, our study bridges gaps between genes, cell classes, biological processes, and brain functional correlates of DCM. While our findings are correlational in nature, they suggest that the neural activities of sensorimotor cortices in DCM are associated with the severity of symptoms and might be associated with neuronal migration within the brain.

Sophoridine alleviates hyperalgesia and anxiety-like behavior in an inflammatory pain mouse model induced by complete freund's adjuvant.

Chronic pain, along with comorbid psychiatric disorders, is a common problem worldwide. A growing number of studies have focused on non-opioid-based medicines, and billions of funds have been put into digging new analgesic mechanisms. Peripheral inflammation is one of the critical causes of chronic pain, and drugs with anti-inflammatory effects usually alleviate pain hypersensitivity. Sophoridine (SRI), one of the most abundant alkaloids in Chinese herbs, has been proved to exert antitumor, antivirus and anti-inflammation effects. Here, we evaluated the analgesic effect of SRI in an inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) injection. SRI treatment significantly decreased pro-inflammatory factors release after LPS stimuli in microglia. Three days of SRI treatment relieved CFA-induced mechanical hypersensitivity and anxiety-like behavior, and recovered abnormal neuroplasticity in the anterior cingulate cortex of mice. Therefore, SRI may be a candidate compound for the treatment of chronic inflammatory pain and may serve as a structural basis for the development of new drugs.

Robotic Gastrectomy Versus Laparoscopic Gastrectomy for Gastric Cancer: A Multicenter Cohort Study of 5402 Patients in China.

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications. RESULTS: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.

End-to-end neural network for pBRDF estimation of object to reconstruct polarimetric reflectance.

Estimating the polarization properties of objects from polarization images is still an important but extremely undefined problem. Currently, there are two types of methods to probe the polarization properties of complex materials: one is about the equipment acquisition, which makes the collection of polarization information unsatisfactory due to the cumbersome equipment and intensive sampling, and the other is to use polarized imaging model for probing. Therefore, the accuracy of the polarized imaging model will be crucial. From an imaging perspective, we propose an end-to-end learning method that can predict accurate, physically based model parameters of polarimetric BRDF from a limited number of captured photographs of the object. In this work, we first design a novel pBRDF model as a powerful prior knowledge. This hybrid pBRDF model completely defines specular reflection, body scattering and directional diffuse reflection in imaging. Then, an end-to-end inverse rendering is performed to connect the multi-view measurements of the object with the geometry and pBRDF parameter estimation, and a reflectance gradient consistency loss is introduced to iteratively estimate the per-pixel normal, roughness, and polarimetric reflectance. Real-world measurement and rendering experiments show that the results obtained by applying our method are in strong agreement with ground truth, validating that we can reproduce the polarization properties of real-world objects using the estimated polarimetric reflectance.

Inhibition of A1 Astrocytes and Activation of A2 Astrocytes for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious injury to the central nervous system that causes significant physical and psychological trauma to the patient. SCI includes primary spinal cord injuries and secondary spinal cord injuries. The secondary injury refers to the pathological process or reaction after the primary injury. Although SCI has always been thought to be an incurable injury, the human nerve has the ability to repair itself after an injury. However, the reparability is limited because glial scar formation impedes functional recovery. There is a type of astrocyte that can differentiate into two forms of reactive astrocytes known as 'A1' and 'A2' astrocytes. A1 astrocytes release cytotoxic chemicals that cause neurons and oligodendrocytes to die and perform a harmful role. A2 astrocytes can produce neurotrophic factors and act as neuroprotectors. This article discusses ways to block A1 astrocytes while stimulating A2 astrocytes to formulate a new treatment for spinal cord injury.

Synthesis of (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-ones from (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oximes and iodobenzenes via a palladium-catalyzed dearomative arylation/oxidation reaction.

A new method has been successfully developed that offers a facile and reliable approach for synthesizing (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-one, providing 28 compounds. This optimized process enables efficient preparation of a wide range of compounds using readily available (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oxime and iodobenzene, and provides alternative ideas for the structural modification of benzofuran ketones.

Ab initio study revealing remarkable oscillatory effects and negative differential resistance in the molecular device of silicon carbide chains.

Inspired by the requirements of miniaturization and multifunction of molecular devices, we investigate the quantum transport properties of three unique molecular devices with silicon carbide chains bridging gold electrodes by an ab initio approach. The pronounced quantum effects, including the oscillation of charge, conductance, and current, together with the negative differential resistance (NDR), have been observed simultaneously over a wide region in the double-chain device. It changes the regular situation that these two effects usually emerge in single-chain systems at the same time. Inspections of the visible differences in the transport behaviors relevant to length and bias between the three devices further evidence that the interchain interaction and molecule-electrode coupling are decisive factors for achieving the quantum effects of oscillation and NDR. These two factors can improve electronic transport capability through enhancing transmission, strengthening the delocalization of frontier molecular orbitals, and reducing potential barriers. Our results not only lay a solid foundation for the application of silicon carbide chains in the miniaturized and multifunctional molecular devices with good performance, but also provide an efficient way to the continuing search for materials with multiple controllable quantum effects in nanoelectronics.