Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression.

How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.

Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

MutL homolog 1 participates in interference-sensitive meiotic crossover formation in soybean.

MutL homolog 1 (MLH1), a member of the MutL-homolog family, is required for normal recombination in most organisms. However, its role in soybean (Glycine max) remains unclear to date. Here, we characterized the Glycine max female and male sterility 1 (Gmfms1) mutation that reduces pollen grain viability and increases embryo sac abortion in soybean. Map-based cloning revealed that the causal gene of Gmfms1 is Glycine max MutL homolog 1 (GmMLH1), and CRISPR/Cas9 knockout approach further validated that disruption of GmMLH1 confers the female-male sterility phenotype in soybean. Loss of GmMLH1 function disrupted bivalent formation, leading to univalent mis-segregation during meiosis and ultimately to female-male sterility. The Gmmlh1 mutant showed about a 78.16% decrease in meiotic crossover frequency compared to the wild type. The residual chiasmata followed a Poisson distribution, suggesting that interference-sensitive crossover formation was affected in the Gmmlh1 mutant. Furthermore, GmMLH1 could interact with GmMLH3A and GmMLH3B both in vivo and in vitro. Overall, our work demonstrates that GmMLH1 participates in interference-sensitive crossover formation in soybean, and provides additional information about the conserved functions of MLH1 across plant species.

Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes.

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear. METHODS: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and Phe508del-gating or Phe508del-residual function genotypes. After a 4-week run-in period with ivacaftor or tezacaftor-ivacaftor, patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or active control for 8 weeks. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 8 in the elexacaftor-tezacaftor-ivacaftor group. RESULTS: After the run-in period, 132 patients received elexacaftor-tezacaftor-ivacaftor and 126 received active control. Elexacaftor-tezacaftor-ivacaftor resulted in a percentage of predicted FEV1 that was higher by 3.7 percentage points (95% confidence interval [CI], 2.8 to 4.6) relative to baseline and higher by 3.5 percentage points (95% CI, 2.2 to 4.7) relative to active control and a sweat chloride concentration that was lower by 22.3 mmol per liter (95% CI, 20.2 to 24.5) relative to baseline and lower by 23.1 mmol per liter (95% CI, 20.1 to 26.1) relative to active control (P<0.001 for all comparisons). The change from baseline in the Cystic Fibrosis Questionnaire-Revised respiratory domain score (range, 0 to 100, with higher scores indicating better quality of life) with elexacaftor-tezacaftor-ivacaftor was 10.3 points (95% CI, 8.0 to 12.7) and with active control was 1.6 points (95% CI, -0.8 to 4.1). The incidence of adverse events was similar in the two groups; adverse events led to treatment discontinuation in one patient (elevated aminotransferase level) in the elexacaftor-tezacaftor-ivacaftor group and in two patients (anxiety or depression and pulmonary exacerbation) in the active control group. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor was efficacious and safe in patients with Phe508del-gating or Phe508del-residual function genotypes and conferred additional benefit relative to previous CFTR modulators. (Funded by Vertex Pharmaceuticals; VX18-445-104 ClinicalTrials.gov number, NCT04058353.).

Decoding the regulatory roles of non-coding RNAs in cellular metabolism and disease.

Non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are being studied extensively in a variety of fields. Their roles in metabolism have received increasing attention in recent years but are not yet clear. The regulation of glucose, fatty acid, and amino acid metabolism is an imperative physiological process that occurs in living organisms and takes part in cancer and cardiovascular diseases. Here, we summarize the important roles played by non-coding RNAs in glucose metabolism, fatty acid metabolism, and amino acid metabolism, as well as the mechanisms involved. We also summarize the therapeutic advances for non-coding RNAs in diseases such as obesity, cardiovascular disease, and some metabolic diseases. Overall, non-coding RNAs are indispensable factors in metabolism and have a significant role in the three major metabolisms, which may be exploited as therapeutic targets in the future.

A confirmatory basket design considering non-inferiority and superiority testing.

For multiple rare diseases as defined by a common biomarker signature, or a disease with multiple disease subtypes of low frequency, it is often possible to provide confirmatory evidence for these disease or subtypes (baskets) as a combined group. A novel drug, as a second generation, may have marginal improvement in efficacy overall but superior efficacy in some baskets. In this situation, it is appealing to test hypotheses of both non-inferiority overall and superiority on certain baskets. The challenge is designing a confirmatory study efficient to address multiple questions in one trial. A two-stage adaptive design is proposed to test the non-inferiority hypothesis at the interim stage, followed by pruning and pooling before testing a superiority hypothesis at the final stage. Such a design enables an efficient and novel registration pathway, including an early claim of non-inferiority followed by a potential label extension with superiority on certain baskets and an improved benefit-risk profile demonstrated by longer term efficacy and safety data. Operating characteristics of this design are examined by simulation studies, and its appealing features make it ready for use in a confirmatory setting, especially in emerging markets, where both the need and the possibility for efficient use of resources may be the greatest.

Understanding the Molecular Regulatory Networks of Seed Size in Soybean.

Soybean being a major cash crop provides half of the vegetable oil and a quarter of the plant proteins to the global population. Seed size traits are the most important agronomic traits determining the soybean yield. These are complex traits governed by polygenes with low heritability as well as are highly influenced by the environment as well as by genotype x environment interactions. Although, extensive efforts have been made to unravel the genetic basis and molecular mechanism of seed size in soybean. But most of these efforts were majorly limited to QTL identification, and only a few genes for seed size were isolated and their molecular mechanism was elucidated. Hence, elucidating the detailed molecular regulatory networks controlling seed size in soybeans has been an important area of research in soybeans from the past decades. This paper describes the current progress of genetic architecture, molecular mechanisms, and regulatory networks for seed sizes of soybeans. Additionally, the main problems and bottlenecks/challenges soybean researchers currently face in seed size research are also discussed. This review summarizes the comprehensive and systematic information to the soybean researchers regarding the molecular understanding of seed size in soybeans and will help future research work on seed size in soybeans.

Biochemical component analysis of human myopic corneal stroma using the Raman spectrum.

PURPOSE: This study aimed to measure the Raman spectrum of the human corneal stroma lens obtained from small incision lenticule extraction surgery (SMILE) in Asian myopic eyes using a confocal Raman micro-spectrometer built in the laboratory. METHODS: Forty-three myopic patients who underwent SMILE with equivalent diopters between - 4.00 and - 6.00 D were selected, and the right eye data were collected. Corneal stroma lenses were obtained during surgery, and the Raman spectra were measured after air drying. The complete Raman spectrum of human myopic corneal stroma lens tissue was obtained within the range of 700-4000 cm-1. RESULTS: Thirteen characteristic peaks were found, with the stronger peaks appearing at 937 cm-1, corresponding to proline, valine, and the protein skeleton of the human myopic corneal stroma lens; 1243 cm-1, corresponding to collagen protein; 1448 cm-1, corresponding to the collagen protein and phospholipids; and 2940 cm-1, corresponding to the amino acid and lipids, which was the strongest Raman peak. CONCLUSION: These results demonstrated that Raman spectroscopy has much potential as a fast, cost-effective, and reliable diagnostic tool in the diagnosis and treatment of eye diseases, including myopia, keratoconus, and corneal infection.

Oviductal Glycoprotein 1 Promotes Hypertension by Inducing Vascular Remodeling Through an Interaction With MYH9.

BACKGROUND: Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classic epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in patients with hypertension is important for investigating hypertension mechanisms. METHODS: Differential genomic DNA methylation in patients with hypertension, individuals with prehypertension, and healthy control individuals was screened using Illumina 450K BeadChip and verified by pyrosequencing. Plasma OVGP1 (oviduct glycoprotein 1) levels were determined using an enzyme-linked immunosorbent assay. Ovgp1 transgenic and knockout mice were generated to analyze the function of OVGP1. The blood pressure levels of the mouse models were measured using the tail-cuff system and radiotelemetry methods. The role of OVGP1 in vascular remodeling was determined by vascular relaxation studies. Protein-protein interactions were investigated using a pull-down/mass spectrometry assay and verified with coimmunoprecipitation and pull-down assays. RESULTS: We found a hypomethylated site at cg20823859 in the promoter region of OVGP1 and plasma OVGP1 levels were significantly increased in patients with hypertension. This finding indicates that OVGP1 is associated with hypertension. In Ovgp1 transgenic mice, OVGP1 overexpression caused an increase in blood pressure, dysfunctional vasoconstriction and vasodilation, remodeling of arterial walls, and increased vascular superoxide stress and inflammation, and these phenomena were exacerbated by angiotensin II infusion. In contrast, OVGP1 deficiency attenuated angiotensin II-induced vascular oxidase stress, inflammation, and collagen deposition. These findings indicate that OVGP1 is a prohypertensive factor that directly promotes vascular remodeling. Pull-down and coimmunoprecipitation assays showed that MYH9 (nonmuscle myosin heavy chain IIA) interacted with OVGP1, whereas inhibition of MYH9 attenuated OVGP1-induced hypertension and vascular remodeling. CONCLUSIONS: Hypomethylation at cg20823859 in the promoter region of OVGP1 is associated with hypertension and induces upregulation of OVGP1. The interaction between OVGP1 and MYH9 contributes to vascular remodeling and dysfunction. Therefore, OVGP1 is a prohypertensive factor that promotes vascular remodeling by binding with MYH9.

Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from a 192-week open-label extension study.

BACKGROUND: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients. METHODS: In this phase 3, open-label, single-arm extension study, participants with F508del-minimal function (from a 24-week parent study; n=399) or F508del-F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary end-point is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit. RESULTS: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (AEs) (586.6 events per 100 participant-years) and serious AEs (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 and 36.9 events per 100 participant-years, respectively); most participants had AEs classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. 14 participants (2.8%) had AEs that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in forced expiratory volume in 1 s (FEV1) percentage predicted, Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbation rates that were maintained over the interim analysis period. The mean annualised rate of change in FEV1 % pred was +0.07 (95% CI -0.12-0.26) percentage points among the participants. CONCLUSIONS: ELX/TEZ/IVA was generally safe and well tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA.

DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma.

BACKGROUND: This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. METHODS: This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. RESULTS: DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. CONCLUSIONS: Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.

GmUFO1 Regulates Floral Organ Number and Shape in Soybean.

The UNUSUAL FLORAL ORGANS (UFO) gene is an essential regulatory factor of class B genes and plays a vital role in the process of inflorescence primordial and flower primordial development. The role of UFO genes in soybean was investigated to better understand the development of floral organs through gene cloning, expression analysis, and gene knockout. There are two copies of UFO genes in soybean and in situ hybridization, which have demonstrated similar expression patterns of the GmUFO1 and GmUFO2 genes in the flower primordium. The phenotypic observation of GmUFO1 knockout mutant lines (Gmufo1) showed an obvious alteration in the floral organ number and shape and mosaic organ formation. By contrast, GmUFO2 knockout mutant lines (Gmufo2) showed no obvious difference in the floral organs. However, the GmUFO1 and GmUFO2 double knockout lines (Gmufo1ufo2) showed more mosaic organs than the Gmufo1 lines, in addition to the alteration in the organ number and shape. Gene expression analysis also showed differences in the expression of major ABC function genes in the knockout lines. Based on the phenotypic and expression analysis, our results suggest the major role of GmUFO1 in the regulation of flower organ formation in soybeans and that GmUFO2 does not have any direct effect but might have an interaction role with GmUFO1 in the regulation of flower development. In conclusion, the present study identified UFO genes in soybean and improved our understanding of floral development, which could be useful for flower designs in hybrid soybean breeding.

Corneal densitometry in bilateral keratoconus patients with unilateral corneal Vogt's striae: a contralateral eye study.

PURPOSE: To investigate corneal densitometry and correlations with corneal morphological parameters in patients with bilateral keratoconus (KC) with unilateral Vogt's striae. METHODS: This prospective contralateral study enrolled 112 patients (224 eyes) with evident KC characteristics (corneal topography with asymmetric bow-tie pattern, inferior steepening), and at least one KC sign (conical protrusion of the cornea at the apex, corneal stromal thinning, Fleischer ring, Vogt's striae) on slit-lamp examination. Corneal densitometry and morphological parameters were measured using Pentacam HR. RESULTS: The mean age was 23.93 ± 6.81 years. Fifty-two (23.22%), 111 (49.55%), and 61 (27.23%) eyes were in mild, moderate, and severe groups, respectively. Corneal densitometry values of the anterior 0-2 mm and 2-6 mm, intermediate 0-2 mm and 2-6 mm, posterior 2-6 mm, and total cornea 2-6 mm were significantly higher in eyes with Vogt's striae (P < 0.05), whereas those of the anterior 6-10 mm, posterior 0-2 mm, and total cornea 6-10 mm were significantly lower in eyes with Vogt's striae (P < 0.05). Anterior 0-2 mm and total cornea 2-6 mm corneal densitometry values were positively correlated with anterior K1 (A-K1), K2 (A-K2), Km (A-Km), Kmax (A-Kmax), anterior corneal elevation, and posterior corneal elevation (P < 0.05), and negatively correlated with central corneal thickness and thinnest corneal thickness in eyes with Vogt's striae (P < 0.05). A-K2, A-Km, and A-Kmax were significantly correlated with the densitometry values of the anterior 0-2 mm and intermediate 0-2 mm in eyes without Vogt's striae (P < 0.05). CONCLUSION: Vogt's striae mainly occur on the anterior and intermediate layers during KC progression.

Diagnostic value of corneal higher-order aberrations in keratoconic eyes.

PURPOSE: This study aimed to investigate the diagnostic value of corneal anterior, posterior, and total higher-order aberrations in keratoconic eyes. METHODS: We enrolled 94 patients (152 eyes) with mild keratoconus (Group 1), 64 patients (101 eyes) with moderate keratoconus (Group 2), and 32 patients (52 eyes) with advanced keratoconus (Group 3) according to the Amsler-Krumeich classification system; 99 healthy controls (197 normal eyes) were likewise enrolled. Anterior, posterior, and total corneal higher-order aberrations were assessed using a rotating Scheimpflug camera. The 3rd-order and 4th-order root-mean-square values were calculated for higher-order aberrations, including coma, spherical, and trefoil aberrations. Differences between keratoconic and normal eyes were analyzed using Kruskal-Wallis tests. Receiver operating characteristic curves were evaluated for the keratoconus and control groups. RESULTS: The differences in coma 90, coma, trefoil, and spherical aberrations, as well as 3rd-order and 4th-order root-mean-square values, were statistically significant between the keratoconus and control groups for all anterior, posterior, and corneal aberrations. The absolute values of these higher-order aberrations were higher in the keratoconus groups than in the control group and increased with keratoconus severity in Groups 1-3. Coma and 3rd-order RMS values showed excellent sensitivity and specificity for discriminating between normal and keratoconus eyes for all anterior, posterior, and corneal aberrations. CONCLUSION: Coma aberrations and 3rd-order root-mean-square values may be valuable for diagnosing keratoconus. Combining these data with topography information may enable the effective and efficient detection of keratoconus in the future.

High expression of HNRNPR in ESCA combined with 18F-FDG PET/CT metabolic parameters are novel biomarkers for preoperative diagnosis of ESCA.

BACKGROUND: The aim of this study was to determine the expression and function of heterogeneous nuclear ribonucleoprotein R (HNRNPR) in esophageal carcinoma (ESCA), the correlation between its expression and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerized tomography scan (PET/CT)-related parameters. We also investigated whether 18F-FDG PET/CT can be used to predict the expression of HNRNPR in ESCA. METHODS: We analyzed patients with ESCA who underwent 18F-FDG PET/CT before surgery, and their tissues were stained with HNRNPR IHC. The associated parameters were derived using the 18F-FDG PET imaging data, and the correlation with the IHC score was evaluated. The Oncomine, TCGA, and GEO datasets were used to investigate HNRNPR expression in the pan- and esophageal cancers, as well as its relationship with N6-methyladenosine (m6A) modification and glycolysis. The R software, LinkedOmics, GeneMANIA, and StringOnline tools were used to perform GO/KEGG, GGI, and PPI analyses on the HNRNPR. RESULTS: HNRNPR is highly expressed in the majority of pan-cancers, including ESCA, and is associated with BMI, weight, and history of reflux in patients with ESCA. HNRNPR is somewhat accurate in predicting the clinical prognosis of ESCA. HNRNPR expression was positively correlated with SUVmax, SUVmean, and TLG in ESCA (p < 0.05). The combination of these three variables provides a strong predictive value for HNRNPR expression in ESCA. GO/KEGG analysis showed that HNRNPR played a role in the regulation of cell cycle, DNA replication, and the Fannie anemia pathway. The analysis of the TCGA and GEO data sets revealed a significant correlation between HNRNPR expression and m6A and glycolysis-related genes. GSEA analysis revealed that HNRNPR was involved in various m6A and glycolysis related-pathways. CONCLUSION: HNRNPR overexpression correlates with 18F-FDG uptake in ESCA and may be involved in the regulation of the cell cycle, m6A modification, and cell glycolysis. 18F-FDG PET/CT-related parameters can predict the diagnostic accuracy of HNRNPR expression in ESCA.

In-situ measurement and cancellation of the light-shift in fiber-coupled atomic magnetometers.

In optical atomic magnetometers (AMs), the light-shift caused by the circularly polarized pumping beam have a significant impact on the response and is also one of the non-negligible sources of the noise. In this paper, we develop a novel method whereby utilizing the symmetry of the frequency response in an AM to measure and cancel the light-shift. Furthermore, we theoretically analyze and experimentally verify a rapid method of magnetic field compensation and the approach is convenient to measure and cancel of the light-shift. Moreover, the influence of intensity and frequency of the pumping beam is also investigated. The proposed method of in - situ measurement and cancellation of light-shift will be particularly profitable to other optical systems based on AMs.

The miR166 mediated regulatory module controls plant height by regulating gibberellic acid biosynthesis and catabolism in soybean.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play critical roles in regulating plant growth and development. Here, we used Short Tandem Target Mimic (STTM) technology to generate soybean (Glycine max (L.) Merr.) miRNA knockdown lines and identify miRNAs that regulate plant height, a key agronomic trait that affects yield. STTM166 successfully silenced miR166 in soybean and upregulated the expression of miR166 target genes, such as ATHB14-LIKE. The miR166 knockdown lines (GmSTTM166) displayed a reduced plant height phenotype. Moreover, GmSTTM166 plants contained lower levels of bioactive gibberellic acid (GA3) than wild-type plants, and application of exogenous GA partially rescued the dwarf phenotype of GmSTTM166. Knockdown of miR166 altered the expression of genes involved in GA biosynthesis and catabolism. Further analysis revealed that ATHB14-LIKE directly represses transcription of the GA biosynthesis genes GmGA1 and GmGA2, while activating transcription of the GA catabolic gene GIBBERLLIN 2 OXIDASE 2 (GmGA2ox2). Collectively, these results reveal a pivotal role for miR166 in the genetic control of plant height in soybean, thereby providing invaluable insights for molecular breeding to improve soybean yield.

Posterior corneal elevation changes and characteristic analysis 1 year after corneal collagen cross-linking for keratoconus.

PURPOSE: To investigate the changes in posterior corneal elevations (PCEs) in the circular areas and local points after corneal collagen cross-linking (CXL) for the treatment of keratoconus. METHODS: Method 1 divided the cornea into 0-2, 2-4, 4-6, and 6-8 mm regions centering on the apex. Method 2 obtained other 34 PCE values of local point that were identified on the nasal, supra-nasal, sub-nasal, superior, inferior, temporal, supra-temporal, and sub-temporal sides of the circle with diameters of 2, 4, 6, and 8 mm, and the apex and thinnest point. RESULTS: Method 1 showed a forward displacement of PCE at 1 month after CXL and then a backward displacement at 3 months. In Method 2, the points on the temporal side of 2 mm and 4 mm showed the same trend. The backward displacements of PCE on the temporal side of 2 mm at 6 months and on the temporal side of 4 mm at 12 months after CXL were both statistically different than those at 1 month after CXL (P < 0.05). No significant forward displacement of PCE was found in all local points in different quadrants at 1 year after CXL. CONCLUSION: The PCEs in circular areas and characteristic points of different diameters in keratoconic eyes after CXL change with time. Local point assessment of the PCE is more clinically significant. In points selected in different quadrants of the cornea, the change in temporal points was more significant after CXL.

Genomic analysis unveils mechanisms of northward invasion and signatures of plateau adaptation in the Asian house rat.

The Asian house rat (AHR), Rattus tanezumi, has recently invaded the northern half of China. The AHR is a highly adaptive rat species that has also successfully conquered the Qinghai-Tibet Plateau (QTP) and replaced the brown rat (BR), R. norvegicus, at the edge of the QTP. Here, we assembled a draft genome of the AHR and explored the mechanisms of its northward invasion and the genetic basis underlying plateau adaptation in this species. Population genomic analyses revealed that the northwardly invasive AHRs consisted of two independent and genetically distinct populations which might result from multiple independent primary invasion events. One invasive population exhibited reduced genetic diversity and distinct population structure compared with its source population, while the other displayed preserved genetic polymorphisms and little genetic differentiation from its source population. Genes involved in G-protein coupled receptors and carbohydrate metabolism may contribute to the local adaptation of northern AHRs. In particular, RTN4 was identified as a key gene for AHRs in the QTP that favours adaptation to high-altitude hypoxia. Coincidently, the physiological performance and transcriptome profiles of hypoxia-exposed rats both showed better hypoxia adaptation in AHRs than in BRs that failed to colonize the heart of the QTP, which may have facilitated the replacement of the BR population by the invading AHRs at the edge of the QTP. This study provides profound insights into the multiple origins of the northwardly invasive AHR and the great tolerance to hypoxia in this species.

High-sensitivity operation of a single-beam atomic magnetometer for three-axis magnetic field measurement.

We demonstrate a single-beam atomic magnetometer (AM) capable of measuring a three-axis magnetic field with high-sensitivity, achieved by applying a small DC offset field and a high frequency modulation field. To satisfy the miniaturization demand of AMs, an elliptically polarized light detuned by 50 GHz from the resonance transition center is employed. The circularly polarized component is used to polarize the alkali-metal atoms, while the linearly polarized light is used to detect the dynamics of the polarized spin under a magnetic field. Based on theoretical analysis, parameters that significantly affect the performance are optimized, and a sensitivity of 20 fT/Hz1/2 in x-axis, 25 fT/Hz1/2 in y-axis, 30 fT/Hz1/2 in z-axis is achieved with a miniature 4 × 4 × 4 mm 87Rb vapor cell. Moreover, we also verify that the operation principle of AMs can be used to null background magnetic fields in-situ with isotropic compensation resolution of 6.7 pT, which provides an effectively precise method for zeroing ambient magnetic field. The high-sensitivity operating of an elliptically-polarized-laser-based magnetometer provides prospective futures for constructing a compact, low-cost AM, which is particularly applicable for non-invasive bio-magnetic imaging such as array-based magnetoencephalography (MEG) and magnetocardiography (MCG).