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Aim To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).Material and methods This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of Results In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8 % (55.6; 82.7) vs. 28.9 % (–9.8; 50,5), p 62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95 % CI: 2.80–34.59; p Conclusion Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.

C-reactive protein (CRP) is a highly conserved pentraxin with pattern recognition receptor–like activities. However, despite being used widely as a clinical marker of inflammation, the in vivo functions of CRP and its roles in health and disease remain largely unestablished. This is, to certain extent, due to the drastically different expression patterns of CRP in mice and rats, raising concerns about whether the functions of CRP are essential and conserved across species and how these model animals should be manipulated to examine the in vivo actions of human CRP. In this review, we discuss recent advances highlighting the essential and conserved functions of CRP across species, and propose that appropriately designed animal models can be used to understand the origin-, conformation-, and localization-dependent actions of human CRP in vivo. The improved model design will contribute to establishing the pathophysiological roles of CRP and facilitate the development of novel CRP-targeting strategies.

The widespread application of isoproturon (IPU) can cause serious pollution to the environment and threaten ecological functions. In this study, the IPU bacterial N-demethylase gene pdmAB was transferred and expressed in the chloroplast of soybean (Glycine max L. 'Zhonghuang13'). The transgenic soybeans exhibited significant tolerance to IPU and demethylated IPU to a less phytotoxic metabolite 3-(4-isopropylphenyl)-1-methylurea (MDIPU) in vivo. The transgenic soybeans removed 98% and 84% IPU from water and soil within 5 and 14 days, respectively, while accumulating less IPU in plant tissues compared with the wild-type (WT). Under IPU stress, transgenic soybeans showed a higher symbiotic nitrogen fixation performance (with higher total nodule biomass and nitrogenase activity) and a more stable rhizosphere bacterial community than the WT. This study developed a transgenic (TS) soybean capable of efficiently removing IPU from its growing environment and recovering a high-symbiotic nitrogen fixation capacity under IPU stress, and provides new insights into the interactions between rhizosphere microorganisms and TS legumes under herbicide stress.

Analyzing scientific advances and networks in NPs research can provide valuable insights into the evolving trends, research gaps, and priorities for future research efforts, highlighting the importance of scientific research in pollution control and risk management of uncontrolled and unknown nanoplastics (NPs) that pose a potential global threat, and have raised concerns in the scientific community and media. A total of 2055 nanoplastics (NPs) studies published from 1995 onwards were retrieved from the Web of Science Core Collection database. Bibliometric methods were applied to assess evolving scientific advances and networks. The general term, “nanoplastics,” was first introduced in 1995 as “intelligent” materials. Before 2009, defined as the ambiguous stage, NPs were produced and applied in many different manufacturing areas and processes. The first research referring to nano-scale plastic particles/debris as potential hazardous contaminants appeared in 2010. Thereafter, the number of annual publications on NPs has increased rapidly, particularly from 2018 onwards. Results showed China published 822 scientific papers, overtaking the United States’ 229 papers, whereas European researches, i.e., the Netherlands, Portugal, German, and the United Kingdom, led in quality and citation with extensive international collaborations. Furthermore, we concluded three main research themes from keyword cluster analysis: environmental monitoring (identification, quantification, fresh-water, marine-environment); environmental behaviors (fate, adsorption, aggregation, transport); and toxicology (toxicity, exposure, ingestion, oxidative stress). Toxicology and environmental behaviors of NPs were the leading themes. An overview of the current understanding of NPs in the above three major themes provides perspectives to identify future research directions based on knowledge gaps, e.g., advancing analytical methods, and exploring the mobility and fate of NPs in different ecosystems. Scientific research on NPs is a key fundamental requirement for their pollution control and risk management. To bridge the gap between research and reality, future efforts are required to promote the dissemination of scientific research findings and encourage actions in engineering, policy, education, etc., to support a sustainable society. Graphical Abstract

ObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.ResultsThe prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.ConclusionThe combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.

BackgroundDepression is a prevalent mental health disorder. Although Internet use has been associated with depression, there is limited data on the association between smartphone use and depressive symptoms. The present study aimed to investigate the relationship between smartphone use and depressive symptoms among older individuals in China.Methods5,244 Chinese older individuals over the age of 60 were selected as the sample from the China Longitudinal Aging Social Survey (CLASS) 2018 dataset. The dependent variable “depression symptoms” was measured using the 9-item Center for Epidemiologic Studies-Depression (CES-D) scale. The study employed multiple linear regression to investigate the relationship between smartphone use (independent variable) and depressive symptoms in older people. Thorough analyses of robustness, sensitivity, and heterogeneity were conducted to ensure the robustness and sensitivity of the findings. Additionally, mediating effect analysis was performed to elucidate the mechanism through which the dependent and independent variables were related.ResultsEmpirical study indicated that smartphone use had a negative impact on depressive symptoms among older adults, specifically leading to a reduction in such symptoms. The above-mentioned result was verified through endogenous and robustness tests. The heterogeneity analysis revealed that older individuals aged 70 years and above, male, and residing in urban areas exhibited a stronger association between smartphone use and depressive symptoms. Furthermore, the mediating effect model indicated that political participation, voluntary participation, and active leisure participation mediated the relationship between smartphone use and lower levels of depression symptoms among the older adults. However, passive leisure participation had a suppressing effect on the relationship between smartphone use and reduced depressive symptoms among the older adults.LimitationsThe causal relationship between variables required further investigation with a longitudinal design.ConclusionThese findings suggested that smartphone use may be considered an intervention to reduce depression symptoms among older people by increasing levels of political participation, voluntary participation, and active leisure participation.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp drop in blood pressure in humans and in core body temperature in animals. We report that the IgE/MC-mediated drop in body temperature in mice associated with anaphylaxis also requires the body’s thermoregulatory neural circuit. This circuit is activated when granule-borne chymase from MCs is deposited on proximal TRPV1 + sensory neurons and stimulates them via protease-activated receptor-1. This triggers the activation of the body’s thermoregulatory neural network, which rapidly attenuates brown adipose tissue thermogenesis to cause hypothermia. Mice deficient in either chymase or TRPV1 exhibited limited IgE-mediated anaphylaxis, and, in wild-type mice, anaphylaxis could be recapitulated simply by systemically activating TRPV1 + sensory neurons. Thus, in addition to their well-known effects on the vasculature, MC products, especially chymase, promote IgE-mediated anaphylaxis by activating the thermoregulatory neural circuit.

Evidence suggested that the use of partial dopamine D2/D3 receptor agonists may be a better choice for the treatment of Parkinson's disease (PD), and the stimulation of 5-HT1A receptors (mainly via nondopaminergic mechanisms) alleviates motor and nonmotor disorders of PD, implying that the multitarget approach may provide a double bonus for the treatment of the disease. In this study, 20 novel 1-(3-((6-fluoropyridin-3-yl)oxy)propyl)piperazine derivatives were designed and synthesized using a bioisosterism approach, and their activities for D2/D3/5-HT1A receptors were further tested. The results showed that several compounds exhibited a multitarget combination of D2/5-HT1A agonism. Compounds 7b and 34c showed agonistic activities on D2/D3/5-HT1A receptor. The EC50 value of 7b for D2/D3/5-HT1A receptor were 0.9/19/2.3 nmol/L, respectively; and the EC50 value of 34c for D2/D3/5-HT1A receptor were 3.3/10/1.4 nmol/L, respectively. In addition, 34c exhibited good metabolic stability (the half-life T 1/2 = 159.7 minutes) in vitro, which is of great significance for the further exploration of multitarget anti-PD drugs.

Australia is the driest inhabited continent on earth, and most of its population is concentrated along the coastal line. In recent years, extreme climate events such as floods and droughts have occurred more frequently. Sydney, as the largest city in Australia, requires a reliable water supply. Many solutions have been conducted to secure its water supply. This paper is focused on future water supply for the Greater Sydney area. The analysis supports the concept that in runoff-rich regions like Greater Sydney, there is no water shortage but a lack of water storage. The novel technology, coastal reservoirs, can increase the storage capacity of freshwater in the sea. The average annual discharge at Shoalhaven River mouth is estimated as 1,334 gigalitres. By comparison, the average annual inflow to the Warragamba Dam, which supplies 80% of Sydney's drinking water, is 1,069 gigalitres. This paper discusses how to apply a Coastal Reservoir at the Shoalhaven River mouth to secure additional water supply for ever-growing Greater Sydney. The proposed reservoir with a capacity of 500 gigalitres could supply 1,000 gigalitres of water per year with a reliability of 90%. A preliminary design of the reservoir is demonstrated.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Research on combined phytotoxicity of perfluorooctanoic acid (PFOA) and nanoparticles is very important for the remediation of PFOA contaminated soil and further assessment for the potential of nano-enhanced phytoremediation. Here, joint effects of PFOA and CuO nanoparticles (nCuO) in plants were studied by exposing radish (Raphanus sativus L.) to PFOA (4 mg/kg) and nCuO (200 and 400 mg/kg) for 30 days, and measuring for contaminant accumulation, radish biomass, photosynthesis profiles and nutrient contents. Results showed that PFOA accumulated highly in radish organs but showed limited effects on radish biomass. nCuO could increase the transfer rate of PFOA from root to shoot and reduce PFOA accumulation in edible root part, but higher nCuO lead to decreased radish biomass. Reversely, PFOA alleviated the adverse effects of nCuO on leaf photosynthesis and root metabolism of vitamins and amino acids. These results provided basics for exploring possibility of nano-enhanced phytoremediation for PFOA soil pollution.

Background and aims C-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI). Methods The effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post–AILI induction in wild-type mice. Results CRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus–mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine. Conclusion Our results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

The photocatalysis-self-Fenton is a novel technology for high-fluent degradation and high mineralization of aqueous organic pollutants.

Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dorsal root and trigeminal ganglia of the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) express similar molecular markers and are protective under physiological conditions. They also serve similar functions in the genesis and maintenance of neuropathic pain, downregulating some of their homeostatic functions and driving pro-inflammatory neuro-glial interactions in the PNS and CNS, i.e. “gliopathy”. However, the role of SGCs in neuropathic pain is not simply as “peripheral astrocytes”. We delineate how these peripheral and central glia participate in neuropathic pain by producing different mediators, engaging different parts of neurons, and becoming active at different stages following nerve injury. Finally, we highlight the recent findings that SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1. Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.

Our understanding of neuropathic itch is limited, due to the lack of relevant animal models. Patients with cutaneous T-cell lymphoma (CTCL) suffer from severe itching. Here we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune cell accumulation, and persistent pruritus. Intradermal CTCL inoculation produces time-dependent changes in nerve innervations in lymphoma-bearing skin. In the early-phase (20 days), CTCL causes hyper-innervations in the epidermis. However, chronic itch is associated with loss of epidermal nerve fibers in the late-phases (40 and 60 days). CTCL is also characterized by marked nerve innervations in mouse lymphoma. Blockade of C-fibers reduced pruritus at early- and late-phases, whereas blockade of A-fibers only suppressed late-phase itch. Intrathecal gabapentin injection reduced late-phase but not early-phase pruritus. IL-31 is upregulated in mouse lymphoma, while its receptor Il31ra was persistently upregulated in Trpv1-expressing sensory neurons in CTCL mice. Intratumoral anti-IL-31 treatment effectively suppressed CTCL-induced scratching and alloknesis (mechanical itch). Finally, intrathecal administration of TLR4 antagonist attenuated pruritus in early and late phases and in both sexes. Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.

Excessive inflammation has been implicated in autism spectrum disorder (ASD), but the underlying mechanisms have not been fully studied. SHANK3 is a synaptic scaffolding protein and mutations of SHANK3 are involved in ASD. Shank3 expression in dorsal root ganglion sensory neurons also regulates heat pain and touch. However, the role of Shank3 in the vagus system remains unknown. We induced systemic inflammation by lipopolysaccharide (LPS) and measured body temperature and serum IL-6 levels in mice. We found that homozygous and heterozygous Shank3 deficiency, but not Shank2 and Trpv1 deficiency, aggravates hypothermia, systemic inflammation (serum IL-6 levels), and sepsis mortality in mice, induced by lipopolysaccharide (LPS). Furthermore, these deficits can be recapitulated by specific deletion of Shank3 in Nav1.8-expressing sensory neurons in conditional knockout (CKO) mice or by selective knockdown of Shank3 or Trpm2 in vagal sensory neurons in nodose ganglion (NG). Mice with Shank3 deficiency have normal basal core temperature but fail to adjust body temperature after perturbations with lower or higher body temperatures or auricular vagus nerve stimulation. In situ hybridization with RNAscope revealed that Shank3 is broadly expressed by vagal sensory neurons and this expression was largely lost in Shank3 cKO mice. Mechanistically, Shank3 regulates the expression of Trpm2 in NG, as Trpm2 but not Trpv1 mRNA levels in NG were significantly reduced in Shank3 KO mice. Our findings demonstrated a novel molecular mechanism by which Shank3 in vagal sensory neurons regulates body temperature, inflammation, and sepsis. We also provided new insights into inflammation dysregulation in ASD.

Land application of biochar has been recommended as an effective soil amendment measure. Nonetheless, the applied biochar can accumulate co-existing contaminants. Meanwhile, nanoparticles formed due to biochar disintegration may facilitate contaminant transport in vadose zone and groundwater, posing a potential risk to the subsurface environment. Here, we show that the presence of pinewood- and rice straw-derived biochar nanoparticles (BCNPs) at parts per million level (~ 20 mg/L) can result in significant mobilization of hydrophobic, nonpolar contaminants (naphthalene and pyrene) and positively charged polar contaminants (trimethoprim and ciprofloxacin) in saturated sandy soil, but slightly inhibits the transport of negatively charged or neutral hydrophilic compounds (sulfamethoxazole and bisphenol A). With supplemental adsorption and desorption experiments we show that the ability of BCNPs in mediating contaminant transport (either enhancing or inhibiting) relies primarily on the extent of irreversible binding of a contaminant to the BCNPs. Sulfide reduction and leaching of organic carbon, two relatively mild (in terms of modification of physicochemical properties, e.g., surface O/C ratio) but widely occurring aging processes, facilitate co-transport of pyrene and bisphenol A with the BCNPs. However, this is mainly the result of increased mobility of the BCNPs (i.e., the carrier), rather than enhanced interactions between the BCNPs and the contaminants being carried. The findings underline the significant effects of BCNPs on the fate and transport of environmental contaminants, and further highlight the important role of aging in affecting environmental behaviors and effects of biochar materials. Graphical Abstract

Microencapsulated phase change materials (MEPCMs) are effective solutions for addressing the issue of leakage that phase change materials (PCMs) face in thermal energy storage devices. Their applications are ubiquitous as PCMs are utilized in industries such as logistics, construction, electronics, etc., thus, an efficient method to prevent problems such as leakage and poor thermal conductivity is to encapsulate the PCM which not only renders it leakage-proof but also impart mechanical strength and enhanced thermal properties. The application of silicon-based additives is one of the most studied methods to impart such desired properties. We discuss the silicon-containing compounds which are commonly employed in core-shell matrix of encapsulated PCMs, namely, siloxanes and silicone, silicon nitride, silicon carbide, silica/SiO2, and other silicon-containing additives as they are able to provide synergistic improvements and exhibit enhanced physical properties. In this review, the different silicon compounds used as additives or main shell matrix are discussed, the general fabrication of the MEPCM and its thermophysical properties will be briefly highlighted. Lastly, we also examine its application and performance in thermal storage and thermal management. We hope to provide a broader perspective of silicon-containing MEPCM for those who are working in the similar field of research.

Humic substances (HS) are the most abundant forms of natural organic matter on the earth surface. Comprised of decomposed plant and animal materials rich in carbon, oxygen, hydrogen, nitrogen, and sulfur complexes, HS facilitate global carbon and nitrogen cycling and the transport of anthropogenic contaminants. While it is known that HS also interact with organisms at different trophic levels to produce beneficial and harmful effects whether HS exert these biological effects through accumulation remains unknown. Current radiolabeling techniques, which only detect the amount of accumulated radiolabels, cannot visualize the transport and accumulation behavior of HS. Here, using a label-free method based on pump-probe microscopy, we show HS entered the protozoan