A comprehensive review of advances in hepatocyte microencapsulation: selecting materials and preserving cell viability.

Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of materials for microencapsulation. Our examination of hepatocyte microencapsulation research highlights that, to date, most studies have been conducted in vitro or using liver failure mouse models, with a notable paucity of experiments on larger mammals. The functionality of microencapsulated hepatocytes is primarily inferred through indirect measures such as urea and albumin production and the rate of ammonia clearance. Furthermore, research on the mechanisms underlying hepatocyte co-microencapsulation remains limited, and the practicality of xenogeneic hepatocyte transplantation requires further validation. The potential of hepatocyte microencapsulation extends beyond the current scope of application, suggesting a promising horizon for liver failure treatment modalities. Innovations in encapsulation materials and techniques aim to enhance cell viability and function, indicating a need for comprehensive studies that bridge the gap between small-scale laboratory success and clinical applicability. Moreover, the integration of bioengineering and regenerative medicine offers novel pathways to refine hepatocyte transplantation, potentially overcoming the challenges of immune rejection and ensuring the long-term functionality of transplanted cells. In conclusion, while hepatocyte microencapsulation and transplantation herald a new era in liver failure therapy, significant strides must be made to translate these experimental approaches into viable clinical solutions. Future research should aim to expand the experimental models to include larger mammals, thereby providing a clearer understanding of the clinical potential of these therapies. Additionally, a deeper exploration into the mechanisms of cell survival and function within microcapsules, alongside the development of innovative encapsulation materials, will be critical in advancing the field and offering new hope to patients with liver failure.

Advancing kidney xenotransplantation with anesthesia and surgery - bridging preclinical and clinical frontiers challenges and prospects.

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and formulating effective immunosuppressive protocols crucial for transplant success. Critical to advancing xenotransplantation into clinical settings are the nuanced considerations of anesthesia and surgical practices required for these complex procedures. The precise genetic modification of porcine kidneys marks a significant leap in addressing the biological and immunological hurdles that have traditionally challenged xenotransplantation. Yet, the success of these transplants hinges on the process of meticulously matching these organs with human recipients, which demands thorough understanding of immunological compatibility, the risk of organ rejection, and the prevention of zoonotic disease transmission. In parallel, the development and optimization of immunosuppressive protocols are imperative to mitigate rejection risks while minimizing side effects, necessitating innovative approaches in both pharmacology and clinical practices. Furthermore, the post-operative care of recipients, encompassing vigilant monitoring for signs of organ rejection, infectious disease surveillance, and psychological support, is crucial for ensuring post-transplant life quality. This comprehensive care highlights the importance of a multidisciplinary approach involving transplant surgeons, anesthesiologists, immunologists, infectiologists and psychiatrists. The integration of anesthesia and surgical expertise is particularly vital, ensuring the best possible outcomes of those patients undergoing these novel transplants, through safe procedural practices. As xenotransplantation moving closer to clinical reality, establishing consensus guidelines on various aspects, including donor-recipient selection, immunosuppression, as well as surgical and anesthetic management of these transplants, is essential. Addressing these challenges through rigorous research and collective collaboration will be the key, not only to navigate the ethical, medical, and logistical complexities of introducing kidney xenotransplantation into mainstream clinical practice, but also itself marks a new era in organ transplantation.

Elucidating cuproptosis in metabolic dysfunction-associated steatotic liver disease.

Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in the disease's development. This connection offers new insights into MASLD's complex pathogenesis, pointing to copper accumulation as a key factor that disrupts lipid metabolism and insulin sensitivity. The identification of cuproptosis as a significant contributor to MASLD underscores the potential for targeting copper-mediated pathways for novel therapeutic approaches. This promising avenue suggests that managing copper levels could mitigate MASLD progression, offering a fresh perspective on treatment strategies. Further investigations into how cuproptosis influences MASLD are essential for unraveling the detailed mechanisms at play and for identifying effective interventions. The focus on copper's role in liver health opens up the possibility of developing targeted therapies that address the underlying causes of MASLD, moving beyond symptomatic treatment to tackle the root of the problem. The exploration of cuproptosis in the context of MASLD exemplifies the importance of understanding metal homeostasis in metabolic diseases and represents a significant step forward in the quest for more effective treatments. This research direction lights path for innovative MASLD management and reversal.

Arresting the bad seed: HDAC3 regulates proliferation of different microglia after ischemic stroke.

The accumulation of self-renewed polarized microglia in the penumbra is a critical neuroinflammatory process after ischemic stroke, leading to secondary demyelination and neuronal loss. Although known to regulate tumor cell proliferation and neuroinflammation, HDAC3's role in microgliosis and microglial polarization remains unclear. We demonstrated that microglial HDAC3 knockout (HDAC3-miKO) ameliorated poststroke long-term functional and histological outcomes. RNA-seq analysis revealed mitosis as the primary process affected in HDAC3-deficent microglia following stroke. Notably, HDAC3-miKO specifically inhibited proliferation of proinflammatory microglia without affecting anti-inflammatory microglia, preventing microglial transition to a proinflammatory state. Moreover, ATAC-seq showed that HDAC3-miKO induced closing of accessible regions enriched with PU.1 motifs. Overexpressing microglial PU.1 via an AAV approach reversed HDAC3-miKO-induced proliferation inhibition and protective effects on ischemic stroke, indicating PU.1 as a downstream molecule that mediates HDAC3's effects on stroke. These findings uncovered that HDAC3/PU.1 axis, which mediated differential proliferation-related reprogramming in different microglia populations, drove poststroke inflammatory state transition, and contributed to pathophysiology of ischemic stroke.

Novel allelic variations in Tannin1 and Tannin2 contribute to tannin absence in sorghum.

Sorghum is an important food crop commonly used for brewing, feed, and bioenergy. Certain genotypes of sorghum contain high concentrations of condensed tannins in seeds, which are beneficial, such as protecting grains from herbivore bird pests, but also impair grain quality and digestibility. Previously, we identified Tannin1 and Tannin2, each with three recessive causal alleles, regulate tannin absence in sorghum. In this study, via characterizing 421 sorghum accessions, we further identified three novel recessive alleles from these two genes. The tan1-d allele contains a 12-bp deletion at position 659 nt and the tan1-e allele contains a 10-bp deletion at position 771 nt in Tannin1. The tan2-d allele contains a C-to-T transition, which results in a premature stop codon before the bHLH domain in Tannin2, and was predominantly selected in China. We further developed KASP assays targeting these identified recessive alleles to efficiently genotype large populations. These studies provide new insights in sorghum domestication and convenient tools for breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01463-y.

Assessment of yield performances for grain sorghum varieties by AMMI and GGE biplot analyses.

Grain sorghum is an exceptional source of dietary nutrition with outstanding economic values. Breeding of grain sorghum can be slowed down by the occurrence of genotype × environment interactions (GEI) causing biased estimation of yield performance in multi-environments and therefore complicates direct phenotypic selection of superior genotypes. Multi-environment trials by randomized complete block design with three replications were performed on 13 newly developed grain sorghum varieties at seven test locations across China for two years. Additive main effects and multiplicative interaction (AMMI) and genotype + genotype × environment (GGE) biplot models were adopted to uncover GEI patterns and effectively identify high-yielding genotypes with stable performance across environments. Yield (YLD), plant height (PH), days to maturity (DTM), thousand seed weight (TSW), and panicle length (PL) were measured. Statistical analysis showed that target traits were influenced by significant GEI effects (p < 0.001), that broad-sense heritability estimates for these traits varied from 0.40 to 0.94 within the medium to high range, that AMMI and GGE biplot models captured more than 66.3% of total variance suggesting sufficient applicability of both analytic models, and that two genotypes, G3 (Liaoza No.52) and G10 (Jinza 110), were identified as the superior varieties while one genotype, G11 (Jinza 111), was the locally adapted variety. G3 was the most stable variety with highest yielding potential and G10 was second to G3 in average yield and stability whereas G11 had best adaptation only in one test location. We recommend G3 and G10 for the production in Shenyang, Chaoyang, Jinzhou, Jinzhong, Yulin, and Pingliang, while G11 for Yili.

Physiological and Transcriptomic Analysis Provides Insights into Low Nitrogen Stress in Foxtail Millet (Setaria italica L.).

Foxtail millet (Setaria italica (L.) P. Beauv) is an important food and forage crop that is well adapted to nutrient-poor soils. However, our understanding of how different LN-tolerant foxtail millet varieties adapt to long-term low nitrogen (LN) stress at the physiological and molecular levels remains limited. In this study, two foxtail millet varieties with contrasting LN tolerance properties were investigated through analyses of physiological parameters and transcriptomics. The physiological results indicate that JG20 (high tolerance to LN) exhibited superior biomass accumulation both in its shoots and roots, and higher nitrogen content, soluble sugar concentration, soluble protein concentration, zeatin concentration in shoot, and lower soluble sugar and soluble protein concentration in its roots compared to JG22 (sensitive to LN) under LN, this indicated that the LN-tolerant foxtail millet variety can allocate more functional substance to its shoots to sustain aboveground growth and maintain high root activity by utilizing low soluble sugar and protein under LN conditions. In the transcriptomics analysis, JG20 exhibited a greater number of differentially expressed genes (DEGs) compared to JG22 in both its shoots and roots in response to LN stress. These LN-responsive genes were enriched in glycolysis metabolism, photosynthesis, hormone metabolism, and nitrogen metabolism. Furthermore, in the shoots, the glutamine synthetase gene SiGS5, chlorophyll apoprotein of photosystem II gene SiPsbQ, ATP synthase subunit gene Sib, zeatin synthesis genes SiAHP1, and aldose 1-epimerase gene SiAEP, and, in the roots, the high-affinity nitrate transporter genes SiNRT2.3, SiNRT2.4, glutamate synthase gene SiGOGAT2, fructose-bisphosphate aldolase gene SiFBA5, were important genes involved in the LN tolerance of the foxtail millet variety. Hence, our study implies that the identified genes and metabolic pathways contribute valuable insights into the mechanisms underlying LN tolerance in foxtail millet.

Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives.

BACKGROUND: The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE: To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN: A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS: An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS: Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS: The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.

The effect of restrictive vs. liberal fluid protocols on ocular parameters in patients undergoing prone spine surgery: a randomized controlled trial.

BACKGROUND: Elevated intraocular pressure (IOP) and optic nerve edema occurring during prone surgeries may cause ocular and optic nerve ischaemia injury. We hypothesized that a liberal fluid protocol might further increase IOP and optic nerve sheath diameter (ONSD) than a restrictive fluid protocol for patients in the prone position. METHODS: A single-centre, prospective and randomized trial was conducted. Patients were randomly allocated into 2 groups: the liberal fluid infusion group, in which repeated bolus doses of Ringer's lactate solution were given to maintain pulse pressure variation (PPV) within 6~9%, and the restrictive fluid infusion group, where PPV was maintained within 13-16%. IOP and ONSD were measured in both eyes at 10min after the anaesthesia induction in the supine position, 10min after the prone position placement, and 1h and 2h since the prone position was placed, at the conclusion of surgery, and returned to the supine position. RESULTS: A total of 97 patients were recruited and completed the study. IOP increased significantly from 12±3mmHg in the supine position to 31±5 mmHg (p<0.001) at the end of surgery in the liberal fluid infusion group and from 12±2 to 28±4 mmHg (p<0.001) in the restrictive fluid infusion group. There was a statistically significant difference in the change of IOP over time between the two groups (p=0.019). ONSD increased significantly from 5.3±0.3mm in the supine position to 5.5±0.3mm (p<0.001) at the end of surgery in both groups (both p<0.001). There was no statistically significant difference in the change of ONSD over time between the two groups (p>0.05). CONCLUSIONS: Compared to the restrictive fluid protocol, the liberal fluid protocol increased IOP but not ONSD in patients undergoing prone spine surgery. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov ( https://clinicaltrials.gov ) prior to patient enrollment, ID: NCT03890510, on March 26, 2019. The principal investigator was Xiao-Yu Yang.

The gut microbiome and metabolome in kidney transplant recipients with normal and moderately decreased kidney function.

BACKGROUND: The kidney transplant recipients (KTRs) were diagnosed with Chronic Kidney Disease after transplantation (CKD-T). CKD-T can be affected by the microbial composition and metabolites. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of CKD-T. METHODS: We collected 100 fecal samples of KTRs and divided them into two groups according to the stage progression of CKD-T. Among them, 55 samples were analyzed by Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of KTRs were comprehensively characterized. RESULTS: As well as significant differences in gut microbiome diversity between the CKD G1-2T group and CKD G3T group. Eight flora including Akkermansia were found to be enriched in CKD G3T group. As compared with CKD G1-2T group, the relative abundance of some amino acid metabolism, glycerophospholipid metabolism, amino acid biosynthesis, carbohydrate metabolism and purine metabolism in CKD G3T group were differential expressed significantly. In addition, fecal metabolome analysis indicated that CKD G3T group had a unique metabolite distribution characteristic. Two differentially expressed metabolites, N-acetylornithine and 5-deoxy-5'-(Methylthio) Adenosine, were highly correlated with serum creatinine, eGFR and cystatin C. The enrichment of gut microbial function in CKD-T is correlated with the expression of gut metabolites. CONCLUSION: Gut microbiome and metabolites in the progression of CKD-T display some unique distribution and expression characteristics. The composition of the gut microbiome and their metabolites appears to be different between patients with CKD G3T and those with CKD G1-2T.

SiNF-YC2 Regulates Early Maturity and Salt Tolerance in Setaria italica.

Early maturity is an important agronomic trait in most crops, because it can solve the problem of planting in stubble for multiple cropping as well as make full use of light and temperature resources in alpine regions, thereby avoiding damage from low temperatures in the early growth period and early frost damage in the late growth period to improve crop yield and quality. The expression of genes that determine flowering affects flowering time, which directly affects crop maturity and indirectly affects crop yield and quality. Therefore, it is important to analyze the regulatory network of flowering for the cultivation of early-maturing varieties. Foxtail millet (Setaria italica) is a reserve crop for future extreme weather and is also a model crop for functional gene research in C4 crops. However, there are few reports on the molecular mechanism regulating flowering in foxtail millet. A putative candidate gene, SiNF-YC2, was isolated based on quantitative trait loci (QTL) mapping analysis. Bioinformatics analysis showed that SiNF-YC2 has a conserved HAP5 domain, which indicates that it is a member of the NF-YC transcription factor family. The promoter of SiNF-YC2 contains light-response-, hormone-, and stress-resistance-related elements. The expression of SiNF-YC2 was sensitive to the photoperiod and was related to the regulation of biological rhythm. Expression also varied in different tissues and in response to drought and salt stress. In a yeast two-hybrid assay, SiNF-YC2 interacted with SiCO in the nucleus. Functional analysis suggested that SiNF-YC2 promotes flowering and improves resistance to salt stress.

Facile synthesis, crystal structure, quantum calculation, and biological evaluations of novel selenenyl sulfide compounds as potential agrochemicals.

BACKGROUND: In order to design compounds with fresh molecular skeleton to break through the limitation of available agrochemicals, a series of 36 novel selenenyl sulfide compounds were chemically synthesized, and their biological activities were fully evaluated against tobacco mosaic virus (TMV), 14 plant pathogenic fungi, three insect species and plant acetohydroxyacid synthase (AHAS). RESULTS: All the target compounds were characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR, selenium-77 (77 Se)-NMR, and high-resolution mass spectrometry (HRMS). The crystal structure of 10j indicated that the Se-S bond was successfully constructed. Compounds 10d, 10h, 10s, 10u, 10aa, 10ac, 10ae, 10ag, and 10ai exhibited 40%, 43%, 39%, 41%, 47%, 46%, 47%, 42%, and 39% anti-TMV activities at 500 mg L-1 , better than that of ribavirin. The median effective concentration (EC50 ) against Sclerotinia sclerotiorum of 10ac was 6.69 mg L-1 and EC50 values against Physalospora piricola and Pyricularia grisea of 10z were 12.25 mg L-1 and 15.27 mg L-1 , respectively, superior to the corresponding values of chlorothalonil. Compounds 10c and 10v demonstrated 100% larvicidal activity against Culex pipiens pallens at 5 mg L-1 , while 10a displayed 100% insecticidal activity against Mythimna separata at 200 mg L-1 . Compounds 10c, 10j, and 10o showed > 60% inhibitions against plant AHAS at 10 µmol L-1 . From the quantum calculation, highest occupied molecular orbital (HOMO) was considered as a factor that affects the anti-TMV activity. CONCLUSION: The preliminary results suggested that more efforts should be devoted to exploring the selenenyl sulfides for the discovery of new leads of antiviral agent, fungicide, insecticide or AHAS inhibitors as potential agrochemicals for crop protection. © 2023 Society of Chemical Industry.

Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets.

OBJECTIVE: Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application. To find a new strategy, we tested a new polymer combination for islet encapsulation and transplantation. Meanwhile, we explored a new site for xenogeneic islet transplantation in mice. METHOD: We synthesized a hydrogel combining alginate plus poly-ethylene-imine (Alg/PEI) for the encapsulation of rat, neonatal porcine, and human islets. Transplantation was performed into the retroperitoneal retro-colic space of diabetic mice. Control mice received free islets under the kidney capsule or encapsulated islets into the peritoneum. The biochemical indexes were measured, and the transplanted islets were harvested for immunohistochemical staining of insulin and glucagon. RESULTS: Mice receiving encapsulated rat, porcine and human islets transplanted into the retroperitoneal space maintained normoglycemia for a median of 275, 145.5, and 146 days, respectively. In contrast, encapsulated xenogeneic islets transplanted into the peritoneum, maintained function for a median of 61, 95.5, and 82 days, respectively. Meanwhile, xenogeneic islets transplanted free into the kidney capsule lost their function within 3 days after transplantation. Immunohistochemical staining of encapsulated rat, porcine and human islets, retrieved from the retroperitoneal space, allowed to distinguish morphological normal insulin expressing ß- and glucagon expressing α-cells at 70, 60, and 100 days post-transplant, respectively. CONCLUSION: Transplantation of Alg/PEI encapsulated xenogeneic islets into the retroperitoneal space provides a valuable new implantation strategy for the treatment of type 1 diabetes.

Diagnostic performance of GcfDNA in kidney allograft rejection: a meta-analysis.

In this comprehensive meta-analysis, our objective was to evaluate the diagnostic utility of graft-derived cell-free DNA (GcfDNA) in kidney allograft rejection and explore associated factors. We conducted a thorough search of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to September 2022. Statistical analysis was executed utilizing Stata 15, Meta-DiSc 1.4, and Review Manager 5.4 software. The combined pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristics (SROC) curve from the synthesis of findings across ten studies were as follows: 0.75 (0.67-0.81), 0.78 (0.72-0.83), 3.36 (2.89-4.35), 0.32 (0.24-0.44), 8.77 (4.34-17.74), and 0.83 (0.80-0.86), respectively. Among the ten studies primarily focused on GcfDNA's diagnostic potential for antibody-mediated rejection (ABMR), the optimal cut-off threshold demonstrated substantial diagnostic efficacy, with pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the summary receiver operating characteristics curve values of 0.83 (0.74-0.89), 0.75 (0.70-0.80), 3.37 (2.64-4.30), 0.23 (0.15-0.36), 14.65 (7.94-27.03), and 0.85 (0.82-0.88), respectively. These results underscore the high diagnostic accuracy of GcfDNA in detecting rejection. Furthermore, the optimal cut-off threshold proves effective in diagnosing ABMR, while a 1% threshold remains a robust diagnostic criterion for rejection. Notably, for ABMR diagnosis, droplet digital PCR digital droplet polymerase chain reaction emerges as a superior method in terms of accuracy when compared to other techniques. Nonetheless, further research is warranted to substantiate these findings.

Isolation and identification of SiCOL5, which is involved in photoperiod response, based on the quantitative trait locus mapping of Setaria italica.

Foxtail millet (Setaria italica) is a versatile grain and fodder crop grown in arid and semi-arid regions. It is an especially important crop for combating malnutrition in certain poverty-stricken areas of the world. Photoperiod sensitivity is a major constraint to the distribution and utilization of foxtail millet germplasm resources. Foxtail millet may be suitable as a model species for studying the photoperiod sensitivity of C4 crops. However, the genetic basis of the photoperiod response of foxtail millet remains poorly studied. To detect the genetic basis of photoperiod sensitivity-related traits, a recombinant inbred line (RIL) population consisting of 313 lines derived from a cross between the spring-sown cultivar "Longgu 3" and the summer-sown cultivar "Canggu 3" was established. The RIL population was genotyped using whole-genome re-sequencing and was phenotyped in four environments. A high-density genetic linkage map was constructed with an average distance between adjacent markers of 0.69 cM. A total of 21 quantitative trait loci (QTLs) were identified by composite interval mapping, and 116 candidate genes were predicted according to gene annotations and variations between parents, among which three genes were considered important candidate genes by the integration and overall consideration of the results from gene annotation, SNP and indel analysis, cis-element analysis, and the expression pattern of different genes in different varieties, which have different photoperiod sensitivities. A putative candidate gene, SiCOL5, was isolated based on QTL mapping analysis. The expression of SiCOL5 was sensitive to photoperiod and was regulated by biological rhythm-related genes. Function analysis suggested that SiCOL5 positively regulated flowering time. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that SiCOL5 was capable of interacting with SiNF-YA1 in the nucleus.

Artificial intelligence using deep neural network learning for automatic location of the interscalene brachial plexus in ultrasound images.

BACKGROUND: Identifying the interscalene brachial plexus can be challenging during ultrasound-guided interscalene block. OBJECTIVE: We hypothesised that an algorithm based on deep learning could locate the interscalene brachial plexus in ultrasound images better than a nonexpert anaesthesiologist, thus possessing the potential to aid anaesthesiologists. DESIGN: Observational study. SETTING: A tertiary hospital in Shanghai, China. PATIENTS: Patients undergoing elective surgery. INTERVENTIONS: Ultrasound images at the interscalene level were collected from patients. Two independent image datasets were prepared to train and evaluate the deep learning model. Three senior anaesthesiologists who were experts in regional anaesthesia annotated the images. A deep convolutional neural network was developed, trained and optimised to locate the interscalene brachial plexus in the ultrasound images. Expert annotations on the datasets were regarded as an accurate baseline (ground truth). The test dataset was also annotated by five nonexpert anaesthesiologists. MAIN OUTCOME MEASURES: The primary outcome of the research was the distance between the lateral midpoints of the nerve sheath contours of the model predictions and ground truth. RESULTS: The data set was obtained from 1126 patients. The training dataset comprised 11 392 images from 1076 patients. The test dataset constituted 100 images from 50 patients. In the test dataset, the median [IQR] distance between the lateral midpoints of the nerve sheath contours of the model predictions and ground truth was 0.8 [0.4 to 2.9] mm: this was significantly shorter than that between nonexpert predictions and ground truth (3.4 mm [2.1 to 4.5] mm; P < 0.001). CONCLUSION: The proposed model was able to locate the interscalene brachial plexus in ultrasound images more accurately than nonexperts. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov) identifier: NCT04183972.

Mechanical Bowel Preparation Is a Risk Factor for Postoperative Delirium as It Alters the Gut Microbiota Composition: A Prospective Randomized Single-Center Study.

Background and Objective: Postoperative delirium (POD) is a frequent complication in patients undergoing gastrectomy. Increasing evidence suggests that abnormal gut microbiota composition may contribute to its morbidity. However, it is unclear whether mechanical bowel preparation would cause postoperative delirium by altering the gut microbiota of patients. This study aimed to investigate the association between mechanical bowel preparation and postoperative delirium in patients undergoing gastrectomy. Methods: A prospective randomized single-center study was performed. A total of 81 patients with gastric cancer were enrolled and randomly assigned to two groups: preparation group and non-preparation group according to whether the patient received MBP before surgery. To diagnose postoperative delirium, we used the 3-Min Diagnostic Interview for Confusion Assessment Method-defined delirium for five successive days after surgery. 16s rRNA gene sequencing was used to investigate changes in the intestinal bacteria. The linear discriminant analysis and effect size (LefSe) analysis were also used to identify the different taxa of fecal microbiota between the postoperative delirium and non-postoperative delirium groups. Results: We found that there was a significant difference in ß-diversity of the gut microbiota between the preparation group and non-preparation group (P = 0.048). Furthermore, patients in the preparation group had a much higher rate of postoperative delirium (13/40, 32.5%) compared with that in non-preparation groups (4/41, 9.8%). Multivariate regression analysis adjusted by other risk factors indicated that mechanical bowel preparation was associated with the occurrence of delirium (odds ratio = 4.792; 95% confidence interval: 1.274-18.028; P = 0.020). When comparing the gut microbiota of patients with and without POD, Bacteroides and Veillonella (genus), which were higher in the preparation group, were also higher in delirium patients (P < 0.05). Genus Olsenella was both relatively higher in the non-preparation group and non-POD group (P < 0.05). Conclusion: Mechanical bowel preparation not only altered the gut microbiota composition of patients with gastric cancer but also increased the incidence of postoperative delirium. Among all the gut microbiota altered by mechanical bowel preparation, Bacteroides and Veillonella genus might be a risk factor of POD. Genus Olsenella might be a beneficial bacteria to reduce the incidence of POD.

Optimized mouse model of embolic MCAO: From cerebral blood flow to neurological outcomes.

The embolic middle cerebral artery occlusion (eMCAO) model mimics ischemic stroke due to large vessel occlusion in humans and is amenable to thrombolytic therapy with rtPA. However, two major obstacles, the difficulty of the eMCAO surgery and unpredictable occurrence of clot autolysis, had impeded its application in mice. In this study, we modified catheters to produce suitable fibrin-rich embolus and optimized the eMCAO model using cerebral blood flow (CBF) monitored by both laser Doppler flowmetry (LDF) and 2D laser speckle contrast imaging (LSCI) to confirm occlusion of MCA. The results showed that longer embolus resulted in higher mortality. There was a compensatory increase in MCA territory perfusion after eMCAO associated with decreased infarct volume; however, this was only partly dependent on recanalization as clot autolysis was only observed in ∼30% of mice. Cortical CBF monitoring with LSCI showed that the size of peri-core area at 3 h displayed the best correlation with infarct volume that is attributed to compensatory collateral blood flow. The peri-core area best predicted functional outcome after eMCAO. In summary, we developed a reliable eMCAO mouse model that better mimics embolic ischemic stroke in humans, which will increase the potential for successful translation of stroke neuroprotective therapies.

SbbHLH85, a bHLH member, modulates resilience to salt stress by regulating root hair growth in sorghum.

bHLH family proteins play an important role in plant stress response. However, the molecular mechanism regulating the salt response of bHLH is largely unknown. This study aimed to investigate the function and regulating mechanism of the sweet sorghum SbbHLH85 during salt stress. The results showed that SbbHLH85 was different from its homologs in other species. Also, it was a new atypical bHLH transcription factor and a key gene for root development in sweet sorghum. The overexpression of SbbHLH85 resulted in significantly increased number and length of root hairs via ABA and auxin signaling pathways, increasing the absorption of Na+. Thus, SbbHLH85 plays a negative regulatory role in the salt tolerance of sorghum. We identified a potential interaction partner of SbbHLH85, which was phosphate transporter chaperone PHF1 and modulated the distribution of phosphate, through screening a yeast two-hybrid library. Both yeast two-hybrid and BiFC experiments confirmed the interaction between SbbHLH85 and PHF1. The overexpression of SbbHLH85 led to a decrease in the expression of PHF1 as well as the content of Pi. Based on these results, we suggested that the increase in the Na+ content and the decrease in the Pi content resulted in the salt sensitivity of transgenic sorghum.

Discovery of ortho-Alkoxy Substituted Novel Sulfonylurea Compounds That Display Strong Herbicidal Activity against Monocotyledon Grasses.

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with ortho-alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.5 g ha-1, 6-11 exhibited more potent herbicidal activity against barnyard grass (Echinochloa crus-galli) and crab grass (Digitaria sanguinalis) than commercial acetohydroxyacid synthase (AHAS; EC 2.2.1.6) inhibitors triasulfuron, penoxsulam, and nicosulfuron at both pre-emergence and postemergence conditions. 6-11 was safe for peanut for postemergence application at this ultralow dosage, suggesting that it could be considered a potential herbicide candidate for peanut fields. Although 6-11 and triasulfuron share similar chemical structures and have close Ki values for plant AHAS, a significant difference has been observed between their LUMO maps from DFT calculations, which might be a possible factor that leads to their different behaviors toward monocotyledon weed species.