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Abstract Background SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects. Methods Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18–45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55–80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg). Results Sixty-two (part 1/2, n = 50/12; age range, 18–42/55–63 years) and 30 subjects (age range, 18–42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2–60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed. Conclusions A single intravenous dose of SHR-1707 at 2–60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development. Trial registration NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov.

Global climate change is intensifying and extreme weather events are occurring frequently, with far-reaching impacts on agricultural production. The Songnen Plain, as an important maize production region in China, faces challenges posed by climate change. This study aims to explore the effects of climate extremes on maize yield and provide a scientific basis for the adaptation of agriculture to climate change in this region. The study focuses on the spatial and temporal evolution characteristics of climate extremes during the maize reproductive period from 1988 to 2020 in the Songnen Plain and their impacts on maize yield. Daily temperature and precipitation data from 11 meteorological stations were selected and combined with maize yield information to assess the spatial and temporal trends of extreme climate indices using statistical methods such as the moving average and Mann–Kendall (M-K) mutation test. Pearson correlation analysis and a random forest algorithm were also used to quantify the degree of influence of extreme climate on maize yield. The results showed that (1) the extreme heat and humidity indices (TN90p, TX90p, CWD, R95p, R10, and SDII) tended to increase, while the cold indices (TN10p, TX10p) and the drought indices (CDD) showed a decreasing trend, suggesting that the climate of the Songnen Plain region tends to be warmer and more humid. (2) The cold indices in the extreme temperature indices showed a spatial pattern of being higher in the north and lower in the south and lower in the west and higher in the east, while the warm indices were the opposite, and the extreme precipitation indices showed a spatial pattern of being higher in the east and lower in the west. (3). Both maize yield and trend yield showed a significant upward trend. Maize meteorological yield showed a fluctuating downward trend within the range of −1.64~0.79 t/hm2. During the 33 years, there were three climatic abundance years, two climatic failure years, and the rest of the years were normal years. (4) The cold index TN10p and warm indices TN90p and CWD were significantly correlated with maize yield, in which TN90p had the highest degree of positive correlation with yield, and in the comprehensive analysis, the importance of extreme climatic events on maize yield was in the order of TN90p, TN10p, and CWD. This study demonstrates the impact of extreme climate indices on maize yield in the Songnen Plain, providing a scientific basis for local agricultural management and decision-making, helping to formulate response strategies to mitigate the negative effects of extreme climate, ensure food security, and promote sustainable agricultural development.

Precipitation unevenness significantly influences the rational allocation of water resources and the management of agricultural irrigation. Based on precipitation data from 29 meteorological stations in Heilongjiang Province, China, from 1961 to 2020, this study calculated the precipitation concentration index (PCI), precipitation concentration degree (PCD), and precipitation concentration period (PCP) to analyze the spatial distribution characteristics of precipitation heterogeneity at three distinct timescales: year, maize growth period, and the four stages of the maize growth period. The findings reveal that the rainy season in Heilongjiang Province commences earlier in the southwest compared with the northeast and northwest, with a primary concentration in July. At the annual scale, PCI in southwestern Heilongjiang Province surpasses that in the southeastern region, displaying an approximate east–west gradient in PCD and PCP values ranging from 0.544 to 0.746 and 196 to 203, respectively. During the growth period scale, precipitation concentrates in the southwest and central regions, occurring earlier than in the northeast and northwest. In contrast to the annual scale, the PCI value is smaller, and precipitation predominantly concentrates in mid and late July. Examining the four stages of the maize growth period, PCD generally exhibits a decreasing gradient from west to east. The highest values of PCI and PCD manifest in the southwestern part of Heilongjiang Province, with precipitation concentrated in the middle of each growth stage. The research results serve as a valuable reference for policymakers and stakeholders involved in water resource allocation and agricultural water management in Heilongjiang Province.

Abstract Background Deciphering the relationship between clinical responses and gene expression profiles may shed light on the mechanisms underlying diseases. Most existing literature has focused on exploring such relationship from cross-sectional gene expression data. It is likely that the dynamic nature of time-series gene expression data is more informative in predicting clinical response and revealing the physiological process of disease development. However, it remains challenging to extract useful dynamic information from time-series gene expression data. Results We propose a statistical framework built on considering co-expression network changes across time from time series gene expression data. It first detects change point for co-expression networks and then employs a Bayesian multiple kernel learning method to predict exposure response. There are two main novelties in our method: the use of change point detection to characterize the co-expression network dynamics, and the use of kernel function to measure the similarity between subjects. Our algorithm allows exposure response prediction using dynamic network information across a collection of informative gene sets. Through parameter estimations, our model has clear biological interpretations. The performance of our method on the simulated data under different scenarios demonstrates that the proposed algorithm has better explanatory power and classification accuracy than commonly used machine learning algorithms. The application of our method to time series gene expression profiles measured in peripheral blood from a group of subjects with respiratory viral exposure shows that our method can predict exposure response at early stage (within 24 h) and the informative gene sets are enriched for pathways related to respiratory and influenza virus infection. Conclusions The biological hypothesis in this paper is that the dynamic changes of the biological system are related to the clinical response. Our results suggest that when the relationship between the clinical response and a single gene or a gene set is not significant, we may benefit from studying the relationships among genes in gene sets that may lead to novel biological insights.

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named "Mapping Allele with Resolved Carrier Status" (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population. [ABSTRACT FROM AUTHOR]