Baseline oxygen consumption decreases with cortical depth.

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase-the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.

Novel and multifaceted regulations of photoperiodic flowering by phytochrome A in soybean.

Photoperiod is an important environmental cue. Plants can distinguish the seasons and flower at the right time through sensing the photoperiod. Soybean is a sensitive short-day crop, and the timing of flowering varies greatly at different latitudes, thus affecting yields. Soybean cultivars in high latitudes adapt to the long day by the impairment of two phytochrome genes, PHYA3 and PHYA2, and the legume-specific flowering suppressor, E1. However, the regulating mechanism underlying phyA and E1 in soybean remains largely unknown. Here, we classified the regulation of the E1 family by phyA2 and phyA3 at the transcriptional and posttranscriptional levels, revealing that phyA2 and phyA3 regulate E1 by directly binding to LUX proteins, the critical component of the evening complex, to regulate the stability of LUX proteins. In addition, phyA2 and phyA3 can also directly associate with E1 and its homologs to stabilize the E1 proteins. Therefore, phyA homologs control the core flowering suppressor E1 at both the transcriptional and posttranscriptional levels, to double ensure the E1 activity. Thus, our results disclose a photoperiod flowering mechanism in plants by which the phytochrome A regulates LUX and E1 activity.

Change in body temperature, not acute-phase reaction, predict anti-Osteoporosis efficacy after the first administration of Zoledronic acid: a prospective observational cohort study.

BACKGROUND: Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. METHODS: This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. RESULTS: (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (ß = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010-0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. CONCLUSIONS: In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. TRIAL REGISTRATION: NCT, NCT03158246. Registered 18/05/2017.

A critical role of the soybean evening complex in the control of photoperiod sensitivity and adaptation.

Photoperiod sensitivity is a key factor in plant adaptation and crop production. In the short-day plant soybean, adaptation to low latitude environments is provided by mutations at the J locus, which confer extended flowering phase and thereby improve yield. The identity of J as an ortholog of Arabidopsis ELF3, a component of the circadian evening complex (EC), implies that orthologs of other EC components may have similar roles. Here we show that the two soybean homeologs of LUX ARRYTHMO interact with J to form a soybean EC. Characterization of mutants reveals that these genes are highly redundant in function but together are critical for flowering under short day, where the lux1 lux2 double mutant shows extremely late flowering and a massively extended flowering phase. This phenotype exceeds that of any soybean flowering mutant reported to date, and is strongly reminiscent of the "Maryland Mammoth" tobacco mutant that featured in the seminal 1920 study of plant photoperiodism by Garner and Allard [W. W. Garner, H. A. Allard, J. Agric. Res. 18, 553-606 (1920)]. We further demonstrate that the J-LUX complex suppresses transcription of the key flowering repressor E1 and its two homologs via LUX binding sites in their promoters. These results indicate that the EC-E1 interaction has a central role in soybean photoperiod sensitivity, a phenomenon also first described by Garner and Allard. EC and E1 family genes may therefore constitute key targets for customized breeding of soybean varieties with precise flowering time adaptation, either by introgression of natural variation or generation of new mutants by gene editing.

Diverse flowering responses subjecting to ambient high temperature in soybean under short-day conditions.

Flowering time is one of important agronomic traits determining the crop yield and affected by high temperature. When facing high ambient temperature, plants often initiate early flowering as an adaptive strategy to escape the stress and ensure successful reproduction. However, here we find opposing ways in the short-day crop soybean to respond to different levels of high temperatures, in which flowering accelerates when temperature changes from 25 to 30 °C, but delays when temperature reaches 35 °C under short day. phyA-E1, possibly photoperiodic pathway, is crucial for 35 °C-mediated late flowering, however, does not contribute to promoting flowering at 30 °C. 30 °C-induced up-regulation of FT2a and FT5a leads to early flowering, independent of E1. Therefore, distinct responsive mechanisms are adopted by soybean when facing different levels of high temperatures for successful flowering and reproduction.

Natural variation of FKF1 controls flowering and adaptation during soybean domestication and improvement.

Soybean (Glycine max) is a major source of protein and edible oil world-wide and is cultivated in a wide range of latitudes. However, it is extremely sensitive to photoperiod, which influences flowering time, maturity, and yield, and severely limits soybean latitude adaptation. In this study, a genome-wide association study (GWAS) identified a novel locus in accessions harboring the E1 allele, called Time of flowering 8 (Tof8), which promotes flowering and enhances adaptation to high latitude in cultivated soybean. Gene functional analyses showed that Tof8 is an ortholog of Arabidopsis FKF1. We identified two FKF1 homologs in the soybean genome. Both FKF1 homologs are genetically dependent on E1 by binding to E1 promoter to activate E1 transcription, thus repressing FLOWERING LOCUS T 2a (FT2a) and FT5a transcription, which modulate flowering and maturity through the E1 pathway. We also demonstrate that the natural allele FKF1bH3 facilitated adaptation of soybean to high-latitude environments and was selected during domestication and improvement, leading to its rapid expansion in cultivated soybean. These findings provide novel insights into the roles of FKF1 in controlling flowering time and maturity in soybean and offer new means to fine-tune adaptation to high latitudes and increase grain yield.

Candidate loci for breeding compact plant-type soybean varieties.

Plant height and node number are important agronomic traits that influence yield in soybean (Glycine max L.). Here, to better understand the genetic basis of the traits, we used two recombinant inbred line (RIL) populations to detect quantitative trait loci (QTLs) associated with plant height and node number in different environments. This analysis detected 9 and 21 QTLs that control plant height and node number, respectively. Among them, we identified two genomic regions that overlap with Determinate stem 1 (Dt1) and Dt2, which are known to influence both plant height and node number. Furthermore, different combinations of Dt1 and Dt2 alleles were enriched in distinct latitudes. In addition, we determined that the QTLs qPH-13-SE and qPH-13-DW in the two RIL populations overlap with genomic intervals associated with plant height and the QTL qNN-04-DW overlaps with an interval associated with node number. Combining the dwarf allele of qPH-13-SE/qPH-13-DW and the multiple-node allele of qNN-04-DW produced plants with ideal plant architecture, i.e., shorter main stems with more nodes. This plant type may help increase yield at high planting density. This study thus provides candidate loci for breeding elite soybean cultivars for plant height and node number. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01352-2.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Risk factors of mortality and second fracture after elderly hip fracture surgery in Shanghai, China.

INTRODUCTION: Hip fracture is one of the leading causes of death and disability in the elderly. We analyzed the risk factors of mortality and second fracture within 2 years after hip fracture surgery in elderly Chinese patients. MATERIALS AND METHODS: A total of 613 elderly patients after hip fracture surgery were selected, including 181 males and 432 females, and the patients were followed for at least 24 months. Information about patients and surgery was collected from medical records. Information on death, secondary fracture, and postoperative activities of daily living (ADL) was obtained by telephone follow-up. Cox regression was performed to identify risk factors associated with mortality and second fracture, measured by hazard ratio (HR). RESULTS: The 1-year and 2-year mortality rates after hip fracture were 13.4% and 20.7%, respectively. The second fracture rate within 2 years was 9.5%. Male gender (HR 1.51, P = 0.035), increased age (HR 1.07, P < 0.001), preoperative hypoalbuminemia (HR 1.79, P = 0.004), preoperative pneumonia (HR 2.60, P = 0.005) and poor ADL (P = 0.048) were independent risk factors for 2-year mortality, while high preoperative hemoglobin (HR 0.98, P = 0.002), high preoperative eGFR (HR 0.99, P = 0.031), high preoperative LVEF (HR 0.92, P = 0.048) were protective factors for 2-year mortality. Poor ADL (P = 0.002) was the independent risk factor for second fracture within 2 years. CONCLUSIONS: The 2-year mortality rate and second fracture rate after hip fracture in elderly remained high, which was related to old age and complications exists. Postoperative rehabilitation and improving ADL were very important to reduce mortality and second fracture.

Agronomical selection on loss-of-function of GIGANTEA simultaneously facilitates soybean salt tolerance and early maturity.

Salt stress and flowering time are major factors limiting geographic adaptation and yield productivity in soybean (Glycine max). Although improving crop salt tolerance and latitude adaptation are essential for efficient agricultural production, whether and how these two traits are integrated remains largely unknown. Here, we used a genome-wide association study to identify a major salt-tolerance locus controlled by E2, an ortholog of Arabidopsis thaliana GIGANTEA (GI). Loss of E2 function not only shortened flowering time and maturity, but also enhanced salt-tolerance in soybean. E2 delayed soybean flowering by enhancing the transcription of the core flowering suppressor gene E1, thereby repressing Flowering Locus T (FT) expression. An E2 knockout mutant e2CR displayed reduced accumulation of reactive oxygen species (ROS) during the response to salt stress by releasing peroxidase, which functions in ROS scavenging to avoid cytotoxicity. Evolutionary and population genetic analyses also suggested that loss-of-function e2 alleles have been artificially selected during breeding for soybean adaptation to high-latitude regions with greater salt stress. Our findings provide insights into the coupled selection for adaptation to both latitude and salt stress in soybean; and offer an ideal target for molecular breeding of early-maturing and salt-tolerant cultivars.