Transcriptome analysis of largemouth bass (Micropterus salmoides) challenged with LPS and polyI:C.

Largemouth bass (Micropterus salmoides) is a worldwide commercially important aquatic species. In recent years, pathogenic diseases cause great economic losses and hinder the industry of largemouth bass. To further understand the immune response against pathogens in largemouth bass, splenic transcriptome libraries of largemouth bass were respectively constructed at 12 h post-challenged with phosphate-buffered saline (PBS), lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (polyI:C) by using RNA sequencing technology (RNA-seq). RNA libraries were constructed using 9 RNA splenic samples isolated from three biological replicates of the three groups and sequenced on the DNBSEQ platform. A total number of 86,306 unigenes were obtained. Through pairwise comparisons among the three groups, we identified 11,295 different expression genes (DEGs) exhibiting significant differences at the transcript level. There were 7, 7, and 13 signal pathways were significantly enriched in LPS-PBS comparison, polyI:C-PBS comparison, and LPS-polyI:C comparison, respectively, indicating that the immune response to different pathogens was distinct in largemouth bass. To the best of our knowledge, this is the first report on the immune response of largemouth bass against different pathogen-associated molecular patterns (PAMPs) stimuli using transcriptomic analysis. Our results provide a valuable resource and new insights to understanding the immune characteristics of largemouth bass against different pathogens.

Curtailing FGF19's mitogenicity by suppressing its receptor dimerization ability.

As a physiological regulator of bile acid homeostasis, FGF19 is also a potent insulin sensitizer capable of normalizing plasma glucose concentration, improving lipid profile, ameliorating fatty liver disease, and causing weight loss in both diabetic and diet-induced obesity mice. There is therefore a major interest in developing FGF19 as a therapeutic agent for treating type 2 diabetes and cholestatic liver disease. However, the known tumorigenic risk associated with prolonged FGF19 administration is a major hurdle in realizing its clinical potential. Here, we show that nonmitogenic FGF19 variants that retain the full beneficial glucose-lowering and bile acid regulatory activities of WT FGF19 (FGF19WT) can be engineered by diminishing FGF19's ability to induce dimerization of its cognate FGF receptors (FGFR). As proof of principle, we generated three such variants, each with a partial defect in binding affinity to FGFR (FGF19ΔFGFR) and its coreceptors, i.e., ßklotho (FGF19ΔKLB) or heparan sulfate (FGF19ΔHBS). Pharmacological assays in WT and db/db mice confirmed that these variants incur a dramatic loss in mitogenic activity, yet are indistinguishable from FGF19WT in eliciting glycemic control and regulating bile acid synthesis. This approach provides a robust framework for the development of safer and more efficacious FGF19 analogs.

PDE1 or PDE5 inhibition augments NO-dependent hypoxic constriction of porcine coronary artery via elevating inosine 3',5'-cyclic monophosphate level.

Hypoxic coronary vasospasm may lead to myocardial ischaemia and cardiac dysfunction. Inosine 3',5'-cyclic monophosphate (cIMP) is a putative second messenger to mediate this pathological process. Nevertheless, it remains unclear as to whether levels of cIMP can be regulated in living tissue such as coronary artery and if so, what is the consequence of this regulation on hypoxia-induced vasoconstriction. In the present study, we found that cIMP was a key determinant of hypoxia-induced constriction but not that of the subsequent relaxation response in porcine coronary arteries. Subsequently, coronary arteries were treated with various phosphodiesterase (PDE) inhibitors to identify PDE types that are capable of regulating cIMP levels. We found that inhibition of PDE1 and PDE5 substantially elevated cIMP content in endothelium-denuded coronary artery supplemented with exogenous purified cIMP. However, cGMP levels were far lower than their levels in intact coronary arteries and lower than cIMP levels measured in endothelium-denuded coronary arteries supplemented with exogenous cIMP. The increased cIMP levels induced by PDE1 or PDE5 inhibition further led to augmented hypoxic constriction without apparently affecting the relaxation response. In intact coronary artery, PDE1 or PDE5 inhibition up-regulated cIMP levels under hypoxic condition. Concomitantly, cGMP level increased to a comparable level. Nevertheless, the hypoxia-mediated constriction was enhanced in this situation that was largely compromised by an even stronger inhibition of PDEs. Taken together, these data suggest that cIMP levels in coronary arteries are regulated by PDE1 and PDE5, whose inhibition at a certain level leads to increased cIMP content and enhanced hypoxic constriction.

Expression and activity analysis of ß Gallinacin-3 in Arabidopsis.

ß Gallinacin-3 (ß Gal-3) is an antimicrobial peptide with strong antibacterial activity against Escherichia coli, Staphylococcus aureus and Salmonella typhimurium. In this study, the ß Gal-3 gene was transferred into a plant genome by genetic engineering techniques. These transgenic plants can be used as feed additives to prevent poultry diseases and them might replace the antibiotics used in poultry industry. To ensure the ß Gal-3 expresses effectively in Arabidopsis seeds, the expression was driven by promoter Ppha cloned from the ß-phaseolin storage protein gene. A total of 294 transgenic lines were obtained by Agrobacterium-mediated transformation into Arabidopsis, and five transgenic lines were selected in which the expression levels of ß Gal-3 were more than 0.10% of the total soluble proteins. The transgenic lines with single locus were identified by Southern blotting. The expression of ß Gal-3 and the highest protein accumulation level (about 4.76 mg/g fresh weight with a maximum of 0.27% of total soluble proteins) was measured by Western blotting and ELISA, respectively. After ultrafiltration by centrifugation, the purity of recombinant ß Gal-3 was up to 73%. Taken together, our data showed that expression of ß Gal-3 with antimicrobial activity is possible and effective in Arabidopsis seeds.

Highly efficient production of functional recombinant human fibroblast growth factor 22 in E. coli and its protective effects on H2O2-lesioned L02 cells.

In the 22 member mammalian FGF family, FGF22 belongs to FGF7 subfamily, and its effects are largely confined to the brain and skin. To explore the functions of FGF22 on other tissues and develop a large-scale production of recombinant human FGF22 (rhFGF22) without a fusion tag, a plasmid encoding human FGF22 (pET3a-rhFGF22) was used to express rhFGF22 in E. coli BL21 (DE3) pLysS. A large amount of rhFGF22 inclusion body protein was obtained. A two-step denaturing method successfully solubilized rhFGF22, and it was refolded and then purified in one step via heparin affinity chromatography. A yield of 105 mg rhFGF22 with a purity of up to 95% was obtained from 100 g wet bacteria. It was found that the rhFGF22 had biological activity, since it effectively attenuated H2O2-induced human hepatic L02 cell death. Analysis by qRT-PCR and Western blot demonstrated that rhFGF22 protects L02 cells from H2O2-induced oxidative damage via suppression of mitochondrial apoptosis pathways. In conclusion, the strategy described in this paper may provide a novel means to solve the production of insoluble rhFGF22 and shine new light on its translational potential.

Seed-specific expression and analysis of recombinant anti-HER2 single-chain variable fragment (scFv-Fc) in Arabidopsis thaliana.

Antibodies to human epidermal growth factor receptor 2 (HER2) are a key element of breast cancer therapy; however, they are expensive to produce and their availability is limited. A seed-specific expression system can be used to produce recombinant proteins. We report a seed-specific expression system for the manufacture of anti-HER2 ScFv-Fc in Arabidopsis thaliana, driven by the Phaseolus vulgaris ß-phaseolin promoter. Recombinant anti-HER2 ScFv-Fc was successfully and specifically expressed in seeds, and identified by protein analysis. The highest protein accumulation level, with a maximum of 1.1% of total soluble protein, was observed in mature seeds. We also demonstrated the anti-tumor potency of the plant-derived antibody against SK-BR-3 cells. These results suggest that seed-expression systems could contribute to the manufacture of commercial antibodies such as anti-HER2 ScFv-Fc.

High production in E. coli of biologically active recombinant human fibroblast growth factor 20 and its neuroprotective effects.

Fibroblast growth factor 20 (FGF20) has a wide range of biological activities; its expression is most pronounced in neural tissues where it has functions in development and neuroprotection. Given these activities, interest in the clinical applications of FGF20 is rising, which will lead to increasing demand for active recombinant human FGF20 (rhFGF20). To improve the production of rhFGF20, an artificial gene encoding fgf20 was cloned into pET3a and expressed in E. coli BL21(DE3)pLysS. By optimizing induction conditions, we successfully induced large amounts of insoluble rhFGF20. Following solubilization and refolding of the rhFGF20 from inclusion bodies, it was purified by HiTrap heparin affinity chromatography to a purity of over 96% with a yield of 218 mg rhFGF20/100 g wet cells. The purified rhFGF20 could stimulate proliferation of both NIH 3T3 cells and PC-12 cells, measured by the MTT assay. In a model of Aß25-35-induced apoptosis on PC-12 cells, rhFGF20 had a clear protective effect. RT-PCR and Western blot analysis of apoptosis-related genes and proteins revealed that the FGF20-derived protective mechanism was likely due to the relief of endoplasmic reticulum stress (ER stress). In conclusion, the approach described here may be a better means to produce active rhFGF20 in good quantity, thereby allowing for its future pharmacological and clinical use.

Expression of bioactive anti-CD20 antibody fragments and induction of ER stress response in Arabidopsis seeds.

Seed-based expression system is an attractive platform for the production of recombinant proteins in molecular farming. Despite the many advantages of molecular farming, little is known about the effect of the different subcellular accumulation of recombinant proteins on the endoplasmic reticulum (ER) quality control system in host plants. In this study, we analyzed the expression of anti-CD20 antibody fragments in seeds of Arabidopsis thaliana (ecotype Columbia) and corresponding glycosylation mutants, and evaluated the influence of three different signal sequences on the expression levels of scFv-Fc of C2B8. The highest protein accumulation level, with a maximum of 6.12 % total soluble proteins, was observed upon fusing proteins to the signal peptide of Arabidopsis seed storage albumin 2. The ER stress responses in developing seeds at 13 days post-anthesis were also compared across different transgenic lines under normal and heat shock conditions. Based on the gene expression profiles of ER stress transducers, our results suggest that accumulation of antibody fragments in the ER exerts more stress on ER homeostasis. In addition, quantitative PCR results also implicate enhanced activation of ER-associated degradation in transgenic lines. Last but not the least, we also demonstrate the anti-tumor potency of plant-derived proteins by showing the anti-tumor activity of purified scFv-Fc proteins against Daudi cells. Together, our data implies that better understanding of the interaction between exogenous protein production and the cellular quality control system of the host plant is necessary for the development of an optimal expression strategy that will be especially beneficial to commercial protein manufacturing.

Emerging activated tungsten dust: Source, environmental behaviors, and health effects.

Fusion energy investigation has stepped to a new stage adopting deuterium and tritium as fuels from the previous stage concentrating hydrogen plasma physics. Special radiation safety issues would be introduced during this stage. In addition to industrial and military uses, tungsten is also regarded as the most promising plasma facing material for fusion reactors. During the operation of fusion reactors, tungsten-based plasma facing materials can be activated via neutron nuclear reaction. Meanwhile, activated tungsten dust can be produced when high-energy plasma interacts with the tungsten-based plasma facing materials, namely plasma wall interaction. Activated tungsten dust would be an emerging environmental pollutant with radiation toxicity containing various radionuclides in addition to the chemical toxicity of tungsten itself. Nonetheless, the historical underestimation of its environmental availability has led to limited research on tungsten compared to other environmental contaminants. This paper presents the first systematic review on the safety issue of emerging activated tungsten dust, encompassing source terms, environmental behaviors, and health effects. The key contents are as follows: 1) to detail the source terms of activated tungsten dust from aspects of tungsten basic properties, generation mechanism, physical morphology and chemical component, radioactivity, as well as potential release pathways, 2) to illustrate the environmental behaviors from aspects of atmospheric dispersion and deposition, transformation and migration in soil, as well as plant absorption and distribution, 3) to identify the toxicity and health effects from aspects of toxicity to plants, distribution in human body, as well as health effects by radiation and chemical toxicity, 4) based on the research progress, research and development issues needed are also pointed out to better knowledge of safety issue of activated tungsten dust, which would be beneficial to the area of fusion energy and ecological impact caused by the routine tungsten related industrial and military applications.

Prevalence, Risk Factors, and Metabolic Characteristics of Metabolically Healthy Obesity in Patients Seeking Bariatric Surgery: A Cohort Study.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight. OBJECTIVE: This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery. METHODS: A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes. RESULTS: Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender (P = .021) and younger age (P < .001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%). CONCLUSION: Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population.

Molecular characterization, structural and expression analysis of twelve CXC chemokines and eight CXC chemokine receptors in largemouth bass (Micropterus salmoides).

The chemokine-receptor system plays important roles in the leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. In the present study, the sequence features, structures and expression patterns of twelve CXC chemokine ligands (CXCL8a.1, CXCL8a.2, CXCL8b.1, CXCL8b.2, CXCL12a, CXCL12b, CXCL13.1, CXCL13.2, CXCL14, CXCL18a, CXCL18b and CXCL19) and eight CXC chemokine receptors (CXCR1, CXCR2, CXCR3.1, CXCR3.2, CXCR3.3, CXCR4a, CXCR4b and CXCR5) of largemouth bass (Micropterus salmoides) were analyzed. All the CXCLs and CXCRs of largemouth bass shared high sequence identities with their teleost counterparts and possessed conserved motifs and structures of CXCLs and CXCRs family. Realtime qPCR revealed that these CXCLs and CXCRs were ubiquitously expressed in all examined tissues, with high expression levels in the immune-related tissues (spleen, head kidney, and gill). Following lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (polyI:C) stimulations, most of these CXCLs and CXCRs were significantly up-regulated in spleen. In addition, the potential interacted molecules of these CXCLs and CXCRs were analyzed by protein-protein interaction network analysis. To the best of our knowledge, this is the first study that in detail analyzes the CXCLs and CXCRs of largemouth bass. Our results provide valuable basis for study the function and mechanism of chemokine-receptor system in largemouth bass.

Celastrol alleviated acute kidney injury by inhibition of ferroptosis through Nrf2/GPX4 pathway.

Ferroptosis is an important pathological process in acute kidney injury (AKI) which could lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). As an active ingredient of Chinese medicine Tripterygium wilfordii, celastrol has been reported to alleviate inflammation and preclinical studies have confirmed its anticancer effect. In the present study, we investigated the renal protective effects of celastrol against cisplatin induced AKI. Mice were administrated cisplatin by intraperitoneal injection and we found that celastrol reduced serum levels of BUN and creatinine, inhibited renal dysfunction, inflammation and oxidative stress. In addition, renal iron accumulation and ferroptosis were significantly reduced by celastrol treatment. Further mechanistic analyses suggested that Nrf2 is essential for celastrol upregulated GPX4 to alleviate ferroptosis and reduction of LDH release, intracellular iron accumulation and lipid peroxidation. These findings expand the potential uses of celastrol for treatment of various kinds of AKI associated with ferroptosis.

Insights into near-surface distribution characteristics of multi-form tritium with consideration of atmospheric buoyancy and gravitational deposition.

Tritium contributes majority to the total airborne radioactive effluents from the nuclear facility because of its considerable production and difficulty in separation. Tritium inventory in the fusion reactor would reach an unprecedented magnitude which brings new safety concern. After being released into the atmosphere, inconsistent atmospheric dispersion behaviors might appear regarding different physicochemical forms such as gaseous state HT, gaseous-aerosol-droplet state HTO. In this study, atmospheric dispersion characteristics of multi-form tritium were investigated based on the computational fluid dynamics method validated by multi-fan type wind tunnel experiments. Species transport model and discrete phase model were used to describe atmospheric dispersion of gaseous and aerosol-droplet state tritium, respectively. Deposition velocity was predicted for gaseous and aerosol-droplet state tritium with different particle sizes. Conditions for describing the changes of particle diameter and its influencing on near-surface tritium distribution due to condensation were provided. The results show that buoyancy effect would strengthen along with the increasing gaseous tritium mass fraction in the airborne effluents. We also indicated that obvious gravitational deposition would appear once gaseous HTO was transformed into droplet state HTO with the particle diameter larger than 20 µm. Both the atmospheric buoyancy and deposition phenomenon would result in a quite different near-surface tritium distribution.

Improved Gaussian plume model for atmospheric dispersion considering buoyancy and gravitational deposition: The case of multi-form tritium.

Various types of radionuclides have different atmospheric dispersion characteristics, such as buoyancy and gravitational deposition phenomenon of light gas and heavy particles, respectively. Gaussian plume model was widely used to describe atmospheric dispersion behaviors of radioactive effluents, particularly for the purpose of engineering environmental impact assessment or nuclear emergency support. Nonetheless, buoyancy and gravitational deposition were rarely reported in previous work for tritium in particular, which might cause a deviation in evaluating near-surface concentration distribution and radiation dose to the public. Based on the multi-form tritium case, we made a quantitative description for the buoyancy and gravitational deposition phenomenon and discussed the feasibility of developing an improved Gaussian plume model to predict near-surface concentration distribution. Firstly, tritium concentration distribution near to the surface was predicted by using computational fluid dynamics method (CFD) and standard Gaussian plume model to reach consistency without consideration of buoyancy and gravitational deposition effects. Secondly, effects of buoyancy and gravitational deposition were identified by species transport model for gaseous tritium and discrete phase model for droplet tritium with integrating the buoyancy force caused by density variation of gaseous tritium and gravitational force of droplet tritium with enough size. Thirdly, buoyancy and gravitational deposition correction factors were obtained to modify the standard Gaussian plume model. Lastly, predictive results by improved Gaussian plume model were compared with CFD method. It was proved the improved correction method enables higher accuracy in predicting the atmospheric concentration distribution of gaseous pollutants with density variation or particles with gravitational deposition properties.

Long-term weight loss outcome of laparoscopic Roux-en-Y gastric bypass predicted by weight loss at 6 months in Chinese patients with BMI ≥ 32.5 kg/m2.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is classic bariatric procedure with long-term safety and efficacy. However, no studies have focused on predicting long-term weight loss after LRYGB in Chinese patients with body mass index (BMI) ≥ 32.5 kg/m2. To explore the relationship between initial and long-term weight loss after LRYGB in patients with BMI ≥ 32.5 kg/m2. All patients were followed-up to evaluate BMI, percentage of excess weight loss (%EWL), and comorbidities. Linear and logistic regression were performed to assess the relationship between initial and long-term weight loss. Receiver operating characteristic curve was used to determine optimal cutoff value. We enrolled 104 patients. The median preoperative BMI was 41.44 (37.92-47.53) kg/m2. %EWL ≥ 50% at 5 years was considered as successful weight loss, and 75.00% of the patients successfully lost weight. The cure rates of hypertension, hyperlipidemia, and type 2 diabetes mellitus at 1 year were 84.38%, 33.93%, and 60.82%, respectively. %EWL at 6 months and 5 years were positively correlated and its relationship could be described by following linear equation: %EWL5 years = 43.934 + 0.356 × %EWL6 months (P < .001; r2 = 0.166). The best cutoff %EWL at 6 months after LRYGB to predict 5-year successful weight loss was 63.93% (sensitivity, 53.85%; specificity, 84.62%; area under the curve (AUC) = 0.671). In Chinese patients with BMI ≥ 32.5 kg/m2, %EWL at 6 months and 5 years were positively correlated and %EWL at 5 years could be calculated by following linear equation: %EWL5 years = 43.934 + 0.356 × %EWL6 months.

Contrasting effects of different light regimes on the photoreactivities of allochthonous and autochthonous chromophoric dissolved organic matter.

Chromophoric dissolved organic matter (CDOM) plays an important role in ultraviolet (UV) light absorption in the ocean. CDOM is known to originate from either an allochthonous or autochthonous source and has varying compositions and levels of reactivity; however, the effects of individual radiation treatments and the combined effects of UVA and UVB on allochthonous and autochthonous CDOM remain poorly understood. Thus, here, we measured changes in the common optical properties of CDOM collected from China's marginal seas and the Northwest Pacific, using full-spectrum, UVA (315-400 nm), and UVB (280-315 nm) irradiation to induce photodegradation over the same time period (60 h). Excitation-emission matrices (EEMs) combined with parallel factor analysis (PARAFAC) identified four components: marine humic-like C1, terrestrial humic-like C2, soil fulvic-like C3, and tryptophan-like C4. Although the behaviours of these components during full-spectrum irradiation exhibited similar decreasing tendencies, three components (C1, C3, and C4) underwent direct photodegradation under UVB exposure, whereas C2 was more susceptible to UVA degradation. The diverse photoreactivities of the source-dependent components to different light treatments led to differing photochemical behaviours of other optical indices [aCDOM(355), aCDOM(254), SR, HIX, and BIX]. The results indicate that irradiation preferentially reduced the high humification degree or humic substance content of allochthonous DOM, and promoted the transformation from the allochthonous humic DOM components to recently produced components. Although values for the samples from different sources overlapped frequently, principal component analysis (PCA) indicated that the overall optical signatures could be linked to the original CDOM source features. The degradation of CDOM humification, aromaticity, molecular weight, and autochthonous fractions under exposure can drive the CDOM biogeochemical cycle in marine environments. These findings can aid in a better understanding of the effects of different combinations of light treatments and CDOM characteristics on CDOM photochemical processes.

rFGF4 alleviates lipopolysaccharide-induced acute lung injury by inhibiting the TLR4/NF-κB signaling pathway.

Acute lung injury (ALI) is a serious and common clinical disease. Despite significant progress in ALI treatment, the morbidity and mortality rates remain high. However, no effective drug has been discovered for ALI. FGF4, a member of the FGF family, plays an important role in the regulation of various physiological and pathological processes. Therefore, in the present study, we aimed to study the protective effects of FGF4 against LPS-induced lung injury in vivo and in vitro. We found that rFGF4 treatment improved the lung W/D weight ratio, the survival rate, immune cell infiltration and protein concentrations in mice with LPS-induced ALI. Histological analysis revealed that rFGF4 significantly attenuated lung tissue injury and cell apoptosis. Furthermore, rFGF4 inhibited the activation of the TLR4/NF-κB signaling pathway and the production of pro-inflammatory mediators in LPS-injured lung tissues, murine alveolar macrophages (MH-S) and murine pulmonary epithelial (MLE-12) cells. The results of cell experiments further verified that rFGF4 inhibited the production of inflammatory mediators in MH-S cells and MLE-12 cells by regulating the TLR4/NF-κB signaling pathway. These results revealed that rFGF4 protected lung tissues and inhibited inflammatory mediators in mice with LPS-induced ALI by inhibiting the TLR4/NF-κB signaling pathway in MH-S and MLE-12 cells.

An integrated high-flux cold atomic beam source for strontium.

We present the design, construction, and characterization of an integrated cold atomic beam source for strontium (Sr), which is based on a compact Zeeman slower for slowing the thermal atomic beam and an atomic deflector for selecting the cold flux. By adopting arrays of permanent magnets to produce the magnetic fields of the slower and the deflector, we effectively reduce the system size and power compared to traditional systems with magnetic coils. After the slower cooling, one can employ additional transverse cooling in the radial direction and improve the atom collimation. The atomic deflectors employ two stages of two-dimensional magnetic-optical trapping (MOT) to deflect the cold flux, whose atomic speed is lower than 50 m/s, by 20° from the thermal atomic beam. We characterize the cold atomic beam flux of the source by measuring the loading rate of a three-dimensional MOT. The loading rates reach up to 109 atoms/s. The setup is compact, highly tunable, lightweight, and requires low electrical power, which addresses the challenge of reducing the complexity of building optical atomic clocks and quantum simulation devices based on Sr.

Sustained remission of type 2 diabetes in rodents by centrally administered fibroblast growth factor 4.

Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite the availability of multiple drugs for short-term management, sustained remission of T2D is currently not achievable pharmacologically. Intracerebroventricular administration of fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents, propelling intense research efforts to understand its mechanism of action. Whether other FGFs possess similar therapeutic benefits is currently unknown. Here, we show that icvFGF4 also elicits a sustained antidiabetic effect in both male db/db mice and diet-induced obese mice by activating FGF receptor 1 (FGFR1) expressed in glucose-sensing neurons within the mediobasal hypothalamus. Specifically, FGF4 excites glucose-excited (GE) neurons while inhibiting glucose-inhibited (GI) neurons. Moreover, icvFGF4 restores the percentage of GI neurons in db/db mice. Importantly, intranasal delivery of FGF4 alleviates hyperglycemia in db/db mice, paving the way for non-invasive therapy. We conclude that icvFGF4 holds significant therapeutic potential for achieving sustained remission of T2D.

Rolling-leaf14 is a 2OG-Fe (II) oxygenase family protein that modulates rice leaf rolling by affecting secondary cell wall formation in leaves.

As an important agronomic trait, leaf rolling in rice (Oryza sativa L.) has attracted much attention from plant biologists and breeders. Moderate leaf rolling increases the amount of photosynthesis in cultivars and hence raises grain yield. Here, we describe the map-based cloning of the gene RL14, which was found to encode a 2OG-Fe (II) oxygenase of unknown function. rl14 mutant plants had incurved leaves because of the shrinkage of bulliform cells on the adaxial side. In addition, rl14 mutant plants displayed smaller stomatal complexes and decreased transpiration rates, as compared with the wild type. Defective development could be rescued functionally by the expression of wild-type RL14. RL14 was transcribed in sclerenchymatous cells in leaves that remained wrapped inside the sheath. In mature leaves, RL14 accumulated mainly in the mesophyll cells that surround the vasculature. Expression of genes related to secondary cell wall formation was affected in rl14-1 mutants, and cellulose and lignin content were altered in rl14-1 leaves. These results reveal that the RL14 gene affects water transport in leaves by affecting the composition of the secondary cell wall. This change in water transport results in water deficiency, which is the major reason for the abnormal shape of the bulliform cells.