Digitalization of toxicology: improving preclinical to clinical translation.

Though the portfolio of medicines that are extending and improving the lives of patients continues to grow, drug discovery and development remains a challenging business on its best day. Safety liabilities are a significant contributor to development attrition where the costliest liabilities to both drug developers and patients emerge in late development or post-marketing. Animal studies are an important and influential contributor to the current drug discovery and development paradigm intending to provide evidence that a novel drug candidate can be used safely and effectively in human volunteers and patients.

Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis.

Objective: Argatroban is a highly promising drug for the treatment of acute ischemic stroke (AIS), but there is currently insufficient strong evidence regarding the efficacy and safety of using Argatroban in the treatment of AIS. Therefore, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of Argatroban in the treatment of AIS.

Methods: Articles on PubMed, Embase and the Cochrane Library databases were searched from these websites' inceptions to 2th February 2023.

CRISPRlnc: a machine learning method for lncRNA-specific single-guide RNA design of CRISPR/Cas9 system.

CRISPR/Cas9 is a promising RNA-guided genome editing technology, which consists of a Cas9 nuclease and a single-guide RNA (sgRNA). So far, a number of sgRNA prediction softwares have been developed. However, they were usually designed for protein-coding genes without considering that long non-coding RNA (lncRNA) genes may have different characteristics.

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected.

GRAS transcription factor PINNATE-LIKE PENTAFOLIATA2 controls compound leaf morphogenesis in Medicago truncatula.

The milestone of compound leaf development is the generation of separate leaflet primordia during the early stages, which involves two linked but distinct morphogenetic events: leaflet initiation and boundary establishment for leaflet separation. Although some progress in understanding the regulatory pathways for each event have been made, it is unclear how they are intrinsically coordinated. Here, we identify the PINNATE-LIKE PENTAFOLIATA2 (PINNA2) gene encoding a newly identified GRAS transcription factor in Medicago truncatula.

Absence of functional deficits in rats following systemic administration of an AAV9 vector despite moderate peripheral nerve and dorsal root ganglia findings: A clinically silent peripheral neuropathy.

Adeno-associated virus (AAV)-based vectors are commonly used for delivering transgenes in gene therapy studies, but they are also known to cause dorsal root ganglia (DRG) and peripheral nerve toxicities in animals. However, the functional implications of these pathologic findings and their time course remain unclear. At 2, 4, 6, and 8 weeks following a single dose of an AAV9 vector carrying human frataxin transgene in rats, non-standard functional assessments, including von Frey filament, electrophysiology, and Rotarod tests, were conducted longitudinally to measure allodynia, nerve conduction velocity, and coordination, respectively.

Magnetic field and gas pressure sensor based on Mach-Zehnder interferometer with micro-groove fabricated by femtosecond laser pulse.

A microgroove type Mach-Zehnder interferometer (MZI) for gas pressure and magnetic field measurements was prepared using a femtosecond laser pulse in a single mode fiber. Due to the interference light passing through the microgroove, changing the refractive index (RI) of the medium in the microgroove will change the optical path difference between the two channels, leading to significant drift of the MZI transmission spectrum, thus achieving the measurement of environmental parameters. When the gas pressure inside the microgroove changes, the RI of the air changes, achieving the measurement of environmental gas pressure.

The MIO1-MtKIX8 module regulates the organ size in Medicago truncatula.

Plant organ size is an important agronomic trait tightly related to crop yield. However, the molecular mechanisms underlying organ size regulation remain largely unexplored in legumes. We previously characterized a key regulator F-box protein MINI ORGAN1 (MIO1)/SMALL LEAF AND BUSHY1 (SLB1), which controls plant organ size in the model legume Medicago truncatula.

A comparative full-length transcriptomic resource provides insight into the perennial monocarpic mass flowering.

Perennial monocarpic mass flowering represents as a key developmental innovation in flowering time diversity in several biological and economical essential families, such as the woody bamboos and the shrubby Strobilanthes. However, molecular and genetic mechanisms underlying this important biodiversity remain poorly investigated. Here, we generated a full-length transcriptome resource incorporated into the BlueOmics database (http://blueomics.

Sex-related differences in retinal function in Wistar rats: implications for toxicity and safety studies.

Wistar Han rats are a preferred strain of rodents for general toxicology and safety pharmacology studies in drug development. In some of these studies, visual functional tests that assess for retinal toxicity are included as an additional endpoint. Although the influence of gender on human retinal function has been documented for more than 6 decades, preclinically it is still uncertain if there are differences in retinal function between naïve male and female Wistar Han rats.

Ultra-sensitive temperature and pressure sensor based on PDMS-based FPI and Vernier effect.

An ultra-sensitive sensor, based on two Fabry-Perot interferometers (FPIs), has been realized for temperature and pressure sensing. A polydimethylsiloxane (PDMS)-based FPI was used as a sensing cavity, and a closed capillary-based FPI was used as a reference cavity for its insensitivity to both temperature and pressure. The two FPIs were connected in series to obtain a cascaded FPIs sensor, showing a clear spectral envelope.

Ultra-High Sensitivity and Temperature-Insensitive Optical Fiber Strain Sensor Based on Dual Air Cavities.

This study proposed an all-fiber Fabry-Perot interferometer (FPI) strain sensor with two miniature bubble cavities. The device was fabricated by writing two axial, mutually close short-line structures via femtosecond laser pulse illumination to induce a refractive index modified area in the core of a single-mode fiber (SMF). Subsequently, the gap between the two short lines was discharged with a fusion splicer, resulting in the formation of two adjacent bubbles simultaneously in a standard SMF.

Salicylic acid inhibits rice endocytic protein trafficking mediated by OsPIN3t and clathrin to affect root growth.

Salicylic acid (SA) plays important roles in different aspects of plant development, including root growth, where auxin is also a major player by means of its asymmetric distribution. However, the mechanism underlying the effect of SA on the development of rice roots remains poorly understood. Here, we show that SA inhibits rice root growth by interfering with auxin transport associated with the OsPIN3t- and clathrin-mediated gene regulatory network (GRN).

Epigenetic modifications: Allusive clues of lncRNA functions in plants.

Long non-coding RNAs (lncRNAs) have been verified as flexible and important factors in various biological processes of multicellular eukaryotes, including plants. The respective intricate crosstalk among multiple epigenetic modifications has been examined to some extent. However, only a small proportion of lncRNAs has been functionally well characterized.

Traditional Chinese Patent Medicine in the Treatment of Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.

The objective of this study was to evaluate the efficacy and safety of Chinese patent medicine compared with western medicine in the treatment of Alzheimer's disease using the Network Meta-analysis. This study retrieved relevant studies from 7 databases, and the retrieval time was from the establishment of each database to June 2022. After the screening, data extraction, and quality assessment, 47 studies were finally analyzed, involving 11 Chinese patent medicines.

Fabricating Air Pressure Sensors in Hollow-Core Fiber Using Femtosecond Laser Pulse.

In this paper, a hollow core fiber was spliced with standard single-mode fibers to form a fiber optic gas pressure sensor, and its sensing characteristics with single hole or multi-holes punched on the hollow core fiber with femtosecond laser pulses were investigated. The experiments demonstrate that the air pressure sensitivity of the single hole sensor was -3.548 nm/MPa, with a linearity of 99.

Introduction of gloved hand to cage induces 22-kHz ultrasonic vocalizations in male albino rats.

Rodents emit ultrasonic vocalizations (USVs) above the human hearing threshold of ~ 20 kHz to communicate emotional states and to coordinate their social interactive behavior. Twenty-two kHz USVs emitted by adult rats have been reported in a variety of aversive social and behavioral situations. They occur not only under painful or restraining conditions but can also be evoked by gentle cutaneous touch or airflow.

Gunao-Yizhi decoction combined with donepezil for vascular dementia: A systematic review and meta-analysis.

Background: Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the treatment of vascular dementia (VaD). However, there is still a lack of systematic evaluation of its efficacy and safety.

Characteristics of members of IGT family genes in controlling rice root system architecture and tiller development.

Root system architecture (RSA) and tiller are important agronomic traits. However, the mechanisms of the IGT family genes regulate RSA and tiller development in different rice varieties remain unclear. In this study, we demonstrated that 38 rice varieties obtained from Yuanyang Hani's terraced fields with different RSA and could be classified into six groups based on the ratio of root length and width.

Genome-Wide Identification and Analysis of Lbd Transcription Factor Genes in and Related Species.

Lateral organ boundaries domain (LBD) proteins are plant-specific transcription factors that play important roles in organ development and stress response. However, the function of genes has not been reported in Euphorbiaceae. In this paper, we used as the main study object and added rubber tree (), cassava ( Crantz) and castor ( L.

High sensitivity gas pressure sensor based on different inner diameter quartz capillary cascading and Vernier effect.

In this paper, a highly sensitive optical fiber gas pressure sensor is proposed and experimentally verified. The sensor is composed of two Fabry-Pérot (F-P) cavities, and two F-P cavities are fabricated by a single-mode fiber and two quartz capillaries with different inner diameters splicing. Among them, the small inner diameter capillary is used as a gas channel connecting the large inner diameter capillary and the external environment.

RNA-Seq analysis reveals the important co-expressed genes associated with polyphyllin biosynthesis during the developmental stages of Paris polyphylla.

Background: Plants synthesize metabolites to adapt to a continuously changing environment. Metabolite biosynthesis often occurs in response to the tissue-specific combinatorial developmental cues that are transcriptionally regulated. Polyphyllins are the major bioactive components in Paris species that demonstrate hemostatic, anti-inflammatory and antitumor effects and have considerable market demands.