Clinicopathological features of kidney injury in patients receiving immune checkpoint inhibitors (ICPi) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy.

Background: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity.

Methods: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy.

Strain-induced recognition of molecular and chirality in cholesteric liquid crystal droplets for distance and curvature sensing.

Chirality is universal in nature and in biological systems, and the chirality of cholesteric liquid crystals (Ch-LC) is both controllable and quantifiable. Herein, a strategy for precise chirality recognition in a nematic LC host within soft microscale confined droplets is reported. This approach facilitates applications in distance and curvature sensing as well as on-site characterization of the overall uniformity and bending movements of a flexible device.

Small RNAs: An expanding world with therapeutic promises.

Small non-coding RNAs (sncRNAs), such as microRNAs (miRNAs), small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs), play essential roles in regulating various cellular and developmental processes. Over the past three decades, researchers have identified novel sncRNA species from various organisms. These molecules demonstrate dynamic expression and diverse functions, and they are subject to intricate regulation through RNA modifications in both healthy and diseased states.

Epithelial dysfunction is prevented by IL-22 treatment in a Citrobacter rodentium-induced colitis model that shares similarities with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal epithelial barrier leading to breach of barrier immunity. Here we identified similar protein expression changes between IBD and Citrobacter rodentium-infected FVB mice with respect to dysregulation of solute transporters as well as components critical for intestinal barrier integrity. We attribute the disease associated changes in the model to the emergence of undifferentiated intermediate intestinal epithelial cells.

FISI: frequency domain integration sequential imaging at 1.26×10 frames per second and 108 lines per millimeter.

High spatial resolution on the image plane (intrinsic spatial resolution) has always been a problem for ultrafast imaging. Single-shot ultrafast imaging methods can achieve high spatial resolution on the object plane through amplification systems but with low intrinsic spatial resolutions. We present frequency domain integration sequential imaging (FISI), which encodes a transient dynamic by an inversed 4f (IFF) system and decodes it using optical spatial frequencies recognition (OFR), which overcomes the limitation of the spatial frequencies recognition algorithm.

Small Noncoding RNAs in Reproduction and Infertility.

Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical intervention such as assisted reproductive therapy. Small noncoding RNAs (sncRNAs) are well-established regulators of mammalian reproduction.

All-optical high spatial-temporal resolution photography with raster principle at 2 trillion frames per second.

A novel single-shot ultrafast all-optical photography with raster principle (OPR) that can capture real-time imaging of ultrafast phenomena is proposed and demonstrated. It consists of a sequentially timed module (STM), spectral-shaping module (SSM), and raster framing camera (RFC). STM and SSM are used for linearly encoding frequency-time mapping and system calibration, respectively.

A new species of Diplolepis Geoffroy (Hymenoptera: Cynipidae: Diplolepidini) from northeastern China.

A new species, Diplolepis valtonyci Zhu, Wang Pujade-Villar sp. nova, is described from Rosa rugosa Thunb. (1784) and R.

Soft-hard hybrid covalent-network polymer sponges with super resilience, recoverable energy dissipation and fatigue resistance under large deformation.

Energy absorption or dissipation ability has been widely developed in tough hydrogels and 3D nano-structured sponges for a variety of applications. However, fully recoverable energy dissipation and fatigue resistance under large deformation is still challenging yet highly desirable. Polymer network with homogeneous chemical crosslinking structures is an efficient way to construct hydrogels with high resilience and fatigue resistance.

Localized modes and dark solitons sustained by nonlinear defects.

Dark solitons and localized defect modes against periodic backgrounds are considered in arrays of waveguides with defocusing Kerr nonlinearity, constituting a nonlinear lattice. Bright defect modes are supported by a local increase in nonlinearity, while dark defect modes are supported by a local decrease in nonlinearity. Dark solitons exist for both types of defects, although in the case of weak nonlinearity, they feature side bright humps, making the total energy propagating through the system larger than the energy transferred by the constant background.

Specification and epigenomic resetting of the pig germline exhibit conservation with the human lineage.

Investigations of the human germline and programming are challenging because of limited access to embryonic material. However, the pig as a model may provide insights into transcriptional network and epigenetic reprogramming applicable to both species. Here we show that, during the pre- and early migratory stages, pig primordial germ cells (PGCs) initiate large-scale epigenomic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and, potentially, base excision repair (BER).

Janus Nanoparticles with Tunable Amphiphilicity for Stabilizing Pickering-Emulsion Droplets via Assembly Behavior at Oil-Water Interfaces.

Janus particles (JNPs) with controlled anisotropies are regarded as promising materials for sophisticated building blocks and assembly. Herein a straightforward method was proposed for the synthesis of uniformly distributed JNPs with controllable anisotropies, showing two compartmental bulbs with different surface wettability. The synthetic strategy is based on the phase separation-induced styrene liquid protrusion on seed poly(styrene--acrylic acid) (CPSAA) nanoparticles via controlled swelling, with the formed polystyrene (PS) and CPSAA compartments corresponding to the amount of monomers.

[Long-term prognosis of vesicoureteral reflux: a follow-up observation of 138 children].

Objective: To study the long-term prognosis of vesicoureteral reflux in children.

Methods: A retrospective analysis was performed for the clinical data of 138 children (218 ureters with reflux) who were diagnosed with vesicoureteral reflux for the first time from November 2005 to March 2017 and received medical treatment and regular follow-up. According to the initial grade of reflux, the ureters with reflux were divided into a low-grade group (141 ureters, grade I-III) and a high-grade group (77 ureters, grade IV-V), and the two groups were compared in terms of clinical data and follow-up results.

Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis.

High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are largely inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development.

Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against .

The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to subspecies infection, leading to maturation of IL-1β and IL-18 and pyroptosis. AIM2 is critical for host protection against infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11.

A bio-inspired model for bidirectional polarisation detection.

This study investigated a novel polarisation detection model based on the microstructure of rhabdom in mantis shrimp eyes, in which a single unit can detect two directions of orthogonal polarisation. The bionic model incorporated multi-layered orthogonal Si wire grids, and the finite-difference time-domain method was used to simulate light absorption. A single-layer Si wire grid was simulated to study the effects of thickness and duty cycle on extinction ratios.

Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice.

Mice deficient in SHANK-associated RH domain-interacting protein (SHARPIN), a component of the linear ubiquitin chain assembly complex (LUBAC), develop a spontaneous inflammatory disorder with pathologic hallmarks similar to atopic dermatitis and psoriasis in humans. Previous studies identified the crucial role of components of the TNF and IL-1 signaling pathways in the progression of disease in SHARPIN-deficient mice. However, an innate immune adaptor or sensor that relates to the disease progression has remained unknown.

A Lexicon of DNA Modifications: Their Roles in Embryo Development and the Germline.

5-methylcytosine (5mC) on CpG dinucleotides has been viewed as the major epigenetic modification in eukaryotes for a long time. Apart from 5mC, additional DNA modifications have been discovered in eukaryotic genomes. Many of these modifications are thought to be solely associated with DNA damage.

IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation.

Inflammasome activation is critical for host defenses against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here, we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone-marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes.

Detrimental Type I Interferon Signaling Dominates Protective AIM2 Inflammasome Responses during Francisella novicida Infection.

Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F.

Perillyl alcohol protects human renal tubular epithelial cells from hypoxia/reoxygenation injury via inhibition of ROS, endoplasmic reticulum stress and activation of PI3K/Akt/eNOS pathway.

Ischemia/reperfusion (I/R) injury plays an essential role in renal transplantation, and represents a crucial risk factor for allograft dysfunction and acute renal failure. Modulation of oxidative stress is an effective therapeutic strategy for I/R injury. Perillyl alcohol (POH), a dietary monoterpene with antioxidant activity is found in a variety of plants.

NLRC3 regulates cellular proliferation and apoptosis to attenuate the development of colorectal cancer.

Nucleotide-binding domain, leucine-rich-repeat-containing proteins (NLRs) are intracellular innate immune sensors of pathogen-associated and damage-associated molecular patterns. NLRs regulate diverse biologic processes such as inflammatory responses, cell proliferation and death, and gut microbiota to attenuate tumorigenesis. In a recent publication in Nature, we identified NLRC3 as a negative regulator of PI3K-mTOR signaling and characterized its potential tumor suppressor function.

Cutting Edge: Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1β.

Interleukin-18 and IL-1β, which are cytokines of the IL-1 family, are synthesized as precursor proteins and activated by the inflammasome via proteolytic processing. IL-1β is only induced in response to inflammatory stimuli, but IL-18 is constitutively expressed. However, how IL-18 and IL-1β expression is regulated by different inflammatory signals remains poorly studied.