An investigation into accidents in laboratories in universities in China caused by human error: A study based on improved CREAM and SPAR-H.

Although considerable research has been devoted to improving safety in university laboratories, accidents, in that environment, have still occurred frequently at the cost of serious injury or even death of laboratory personnel. Currently, few Human Reliability Analyses (HRA) have been conducted with respect to a university laboratory. The aim of the research was to conduct a reliability study relating to human behaviour in a university laboratory to explore quantitatively the causes and influencing factors relating to the frequency of laboratory accidents. Improved Cognitive Reliability and Error Analysis Method (CREAM) and improved Standardized Plant Analysis Risk HRA (SPAR-H) were employed to assess Human Error Probability (HEP) of 23 subjects. The HEP calculated through improved CREAM proved more accurate than results obtained through improved SPAR-H. Unexpectedly, the results demonstrated that under similar environmental conditions, the HEP of subjects did not decrease with an increase in educational background, including additional experimental time and experience. Moreover, environmental conditions exerted greater impact on personnel reliability than Human Inherent Factors (HIFs) in laboratories. It is anticipated that the study would provide valuable insights, in respect of research methods, and to serve as a practical basis for lowering the accident rate in university laboratories.

TGR5 supresses cGAS/STING pathway by inhibiting GRP75-mediated endoplasmic reticulum-mitochondrial coupling in diabetic retinopathy.

Diabetic retinopathy (DR) is a serious and relatively under-recognized complication of diabetes. Müller glial cells extend throughout the retina and play vital roles in maintaining retinal homeostasis. Previous studies have demonstrated that TGR5, a member of the bile acid-activated GPCR family, could ameliorate DR. However, the role of TGR5 in regulating Müller cell function and the underlying mechanism remains to be ascertained. To address this, high glucose (HG)-treated human Müller cells and streptozotocin-treated Sprague-Dawley rats were used in the study. The IP3R1-GRP75-VDAC1 axis and mitochondrial function were assessed after TGR5 ablation or agonism. Cytosolic mitochondrial DNA (mtDNA)-mediated cGAS-STING activation was performed. The key markers of retinal vascular leakage, apoptosis, and inflammation were examined. We found that mitochondrial Ca2+ overload and mitochondrial dysfunction were alleviated by TGR5 agonist. Mechanically, TGR5 blocked the IP3R1-GRP75-VDAC1 axis mediated Ca2+ efflux from the endoplasmic reticulum into mitochondria under diabetic condition. Mitochondrial Ca2+ overload led to the opening of the mitochondrial permeability transition pore and the release of mitochondrial DNA (mtDNA) into the cytosol. Cytoplasmic mtDNA bound to cGAS and upregulated 2'3' cyclic GMP-AMP. Consequently, STING-mediated inflammatory responses were activated. TGR5 agonist prevented retinal injury, whereas knockdown of TGR5 exacerbated retinal damage in DR rats, which was rescued by the STING inhibitor. Based on the above results, we propose that TGR5 might be a novel therapeutic target for the treatment of DR.

A Rule for Response Sensitivity of Structural-Color Photonic Colloids.

To mimic natural photonic crystals having color regulation capacities dynamically responsive to the surrounding environment, periodic assembly structures have been widely constructed with response materials. Beyond monocomponent materials with stimulus responses, binary and multiphase systems generally offer extended color space and complex functionality. Constructing a rule for predicting response sensitivity can provide great benefits for the tailored design of intelligently responsive photonic materials. Here, we elucidate mathematical relationships between the response sensitivity of dynamically structural-color changes and the location distances of photonic co-phases in three-dimensional Hansen space that can empirically express the strength of their interaction forces, including dispersion force, polarity force, and hydrogen bonding. Such an empirical rule is proven to be applicable for some typical alcohols, acetone, and acetic acid regardless of their molecular structures, as verified by angle resolution spectroscopy, in situ infrared spectroscopy, and molecular simulation. The theoretical method we demonstrate provides rational access to custom-designed responsive structural coloration.

Construction of cellulose structural-color pigments with tunable colors and iridescence/non-iridescence.

Structural colorations have been recognized as a significant way to replace conventional organic dyes for paints, inks, packaging, and cosmetics because of brilliant colors, high stability, and eco-friendliness. However, most current structural-color pigments present an iridescent appearance, and it remains difficult to mitigate a trade-off between lowering the iridescence effect and maintaining the color saturation and brightness. Here, we demonstrate a universal yet economical approach to prepare cellulose structural-color pigments with different sizes. A combined ultrasonication and grinding treatment is explored to adjust the pigment colors as well as control the iridescence-to-non-iridescence transition that depends on the pigment size. The cellulose pigments can be applied on irregular and curved surfaces, having high water-, chemical-, and mechanical-resistances. With humidity-sensing behaviors, the pigments can be further integrated into monitoring systems for environmental management. Such a preparation strategy overcomes the limitation of controlling iridescent and non-iridescent structural colors without sacrificing color properties, which may bring more opportunities to develop new eco-friendly pigments for wide applications.

An extracellular matrix-inspired self-healing composite hydrogel for enhanced platelet-rich plasma-mediated chronic diabetic wound treatment.

Diabetes is generally accompanied by difficult-to-heal wounds, which often lead to permanent disability and even death of patients. Because of the abundance of a variety of growth factors, platelet rich plasma (PRP) has been proven to have great clinical potential for diabetic wound treatment. However, how to suppress the explosive release of its active components while realizing adaptability to different wounds remains important for PRP therapy. Here, an injectable, self-healing, and non-specific tissue-adhesive hydrogel formed by oxidized chondroitin sulfate and carboxymethyl chitosan was designed as an encapsulation and delivery platform for PRP. With a dynamic cross-linking structural design, the hydrogel can meet the clinical demands of irregular wounds with controllable gelation and viscoelasticity. Inhibition of PRP enzymolysis as well as sustained release of its growth factors is realized with the hydrogel, enhancing cell proliferation and migration in vitro. Notably, greatly accelerated healing of full thickness wounds of diabetic skins is enabled by promoting the formation of granulation tissues, collagen deposition and angiogenesis as well as reducing inflammation in vivo. This self-healing and extracellular matrix-mimicking hydrogel provides powerful assistance to PRP therapy, enabling its promising applications for the repair and regeneration of diabetic wounds.

[Quantitative Analysis of Spatio-temporal Evolution Characteristics of Seasonal Average Maximum Temperature and Its Influence by Atmospheric Circulation in China from 1950 to 2019].

Global warming and intensified human activities have led to regional climate instability with increasing frequency and the persistence of high-temperature climate events. Eco-environmental protection and socio-economic development have been faced with rigorous threats. Taking the monthly maximum temperatures from 1950 to 2019 as the basic data source, the spatial-temporal evolution characteristics of seasonal average maximum temperature (AMT) were discerned using the Mann-Kendall test and unary linear regression method in China from 1950 to 2019. Combined with linear correlation, partial linear correlation, and wavelet analysis, the correlation between seasonal AMT characteristics and atmospheric circulations was analyzed quantitatively. The results showed that:① the AMT in all seasons had a significant upward trend, with an increase of 1.21, 0.08, 1.81, and 0.25℃ in spring, summer, autumn, and winter, respectively. The abrupt change times of the AMT were concentrated in the 1990s to the early 21st century. ② In terms of spatial distribution, except for in summer, the average trend rates of AMT in other seasons increased gradually from south to north, although the increasing degrees were different. Among them, the AMT change rate in spring-winter was the fastest in northeast and northwest China. ③ There were complex correlations between the AMT of every season and atmospheric circulation factors, and the distribution of the interrelation energy varied significantly in different frequency domains. Specifically, the Pacific Decadal Oscillation had a significant negative correlation with AMT in summer. The North Atlantic Oscillation had an active effect on AMT changes in summer, autumn, and winter. The Arctic Oscillation had a significant positive driving effect on AMT in all seasons, and there were significant positive or negative influences on the short-or long-term changes of AMT in spring and summer due to the different EI Niño-Southern Oscillation years. These results could provide a theoretical basis and technical reference for China to formulate scientific and effective response plans of climate change.

GRP75 Modulates Endoplasmic Reticulum-Mitochondria Coupling and Accelerates Ca2+-Dependent Endothelial Cell Apoptosis in Diabetic Retinopathy.

Endoplasmic reticulum (ER) and mitochondrial dysfunction play fundamental roles in the pathogenesis of diabetic retinopathy (DR). However, the interrelationship between the ER and mitochondria are poorly understood in DR. Here, we established high glucose (HG) or advanced glycosylation end products (AGE)-induced human retinal vascular endothelial cell (RMEC) models in vitro, as well as a streptozotocin (STZ)-induced DR rat model in vivo. Our data demonstrated that there was increased ER-mitochondria coupling in the RMECs, which was accompanied by elevated mitochondrial calcium ions (Ca2+) and mitochondrial dysfunction under HG or AGE incubation. Mechanistically, ER-mitochondria coupling was increased through activation of the IP3R1-GRP75-VDAC1 axis, which transferred Ca2+ from the ER to the mitochondria. Elevated mitochondrial Ca2+ led to an increase in mitochondrial ROS and a decline in mitochondrial membrane potential. These events resulted in the elevation of mitochondrial permeability and induced the release of cytochrome c from the mitochondria into the cytoplasm, which further activated caspase-3 and promoted apoptosis. The above phenomenon was also observed in tunicamycin (TUN, ER stress inducer)-treated cells. Meanwhile, BAPTA-AM (calcium chelator) rescued mitochondrial dysfunction and apoptosis in DR, which further confirmed of our suspicions. In addition, 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, was shown to reverse retinal dysfunction in STZ-induced DR rats in vivo. Taken together, our findings demonstrated that DR fueled the formation of ER-mitochondria coupling via the IP3R1-GRP75-VDAC1 axis and accelerated Ca2+-dependent cell apoptosis. Our results demonstrated that inhibition of ER-mitochondrial coupling, including inhibition of GRP75 or Ca2+ overload, may be a potential therapeutic target in DR.

Highly Flame-Retardant and Low Heat/Smoke-Release Wood Materials: Fabrication and Properties.

Wood is an important renewable material exhibiting excellent physical and mechanical properties, environmental friendliness, and sustainability, and has been widely applied in daily life. However, its inherent flammability and susceptibility to fungal attack greatly limit its application in many areas. Use of fire-retardant coatings and preservatives has endowed wood with improved safety performance; importantly, the cooperative effect of dual treatments on the burning behavior and flame retardancy of wood needs to be better understood. Here, a two-step treatment for wood is proposed, with a copper-boron preservative (CBP) and a fire-retardant coating. The thermal degradation and burning behavior of treated wood were investigated. The CBP formed a physical barrier on the wood surface, facilitating a charring process at high temperatures and thus suppressing the release of heat and smoke. Notably, the dual-treated wood exhibited lower heat release and reduced smoke emission compared with the mono-treated wood, indicating a cooperative effect between CBP and fire-retardant coatings, beneficial to the improvement of fire safety. This experimental work improved fire retardance and suppressed smoke release in flammable materials, and offers a new design for developing fire-retardant coatings.

A Surface Diffusion Barrier Strategy toward Water-Resistant Photonic Materials for Accurate Detection of Ethanol.

Photonic materials that enable visual detection of chemicals have shown great potential for wide applications in chemical, environmental, biotechnological, and food industries, but until now, using hydrophilic photonic materials for tracing water-soluble chemicals remains a major challenge due to the strong water interference. Here, we demonstrate a two-step co-assembly and subsequent surface coating strategy to develop an ethanol-sensitive and anti-water interference photonic crystal film. By using citric acid as a co-assembly phase, high ethanol sensing is realized because of the strong intermolecular affinity. By controlling the thickness of the outer polyvinyl butyral layer, selective ethanol penetration but a water barrier is enabled. Notably, the composite photonic films are free-standing, highly flexible, and controllably structurally colored. We further present using the composite film to quantitatively trace ethanol/water mixtures and potentially track drunk driving as a colorimetric sensor. The heuristic two-step modification strategy proposed in this work not only overcomes the limitation of water interference for hydrophilic colorimetric sensors but also provides references to develop more new photonic materials with water resistance that need to be applied in water/humid environments.

Photonic Cellulose Films with Vivid Structural Colors: Fabrication and Selectively Chemical Response.

Recent advances in structural-color cellulose nanocrystal (CNC) materials have been made toward chemical sensing applications; however, such materials lack sufficient color chroma for naked-eye observation, and their selective recognition to given chemicals as well as the corresponding mechanism has rarely been reported. Here, a dopamine-infiltration and post-polymerization approach is proposed to construct vivid structural-color composite films. The chiral nematic structure of CNC enables the structural coloration, while the strong light absorption of the polymeric co-phase, polydopamine (PDA) enhances the color chroma and visibility. By controlling the PDA amount, the composite films can detect organic solvents quantitatively and selectively via visible color changes. From the viewpoint of the compatibility and similitude principle, notably, a critical solubility parameter distance (R0) between PDA and "active" solvents is defined with a three-dimensional Hansen solubility sphere; this well constructs a rule for the sensing selectivity of the chemochromic composite films. The findings pave the foundation for the design of colorimetric sensors with specifically testing objects.

Ubiquitin Extension Protein UEP1 Modulates Cell Death and Resistance to Various Pathogens in Tobacco.

Ubiquitin (Ub) extension proteins (UEPs) are fusion proteins of a Ub at the N terminus to a ribosomal protein. They are the main source of Ub and the only source of extension ribosomal protein. Although important roles of the Ub-26S proteasome system in various biological processes have been well established, direct evidence for the role of UEP genes in plant defense is rarely reported. In this study, we cloned a Ub-S27a-type UEP gene (NbUEP1) from Nicotiana benthamiana and demonstrated its function in cell death and disease resistance. Virus-induced gene silencing of NbUEP1 led to intensive cell death, culminating in whole-seedling withering. Transient RNA interference (RNAi) of NbUEP1 caused strong cell death in infiltrated areas, while stable NbUEP1-RNAi tobacco plants constitutively formed necrotic lesions in leaves. NbUEP1-RNAi plants exhibited increased resistance to the oomycete Pythium aphanidermatum and viruses Tobacco mosaic virus and Cucumber mosaic virus while displaying decreased resistance to the nematode Meloidogyne incognita compared with non-RNAi control plants. Transcription profiling analysis indicated that jasmonate and ethylene pathways, lipid metabolism, copper amine oxidase-mediated active species generation, glycine-rich proteins, vacuolar processing enzyme- and RD21-mediated cell death and defense regulation, and autophagy might be associated with NbUEP1-mediated cell death and resistance. Our results provided evidence for the important roles of plant UEPs in modulating plant cell death and disease resistance.

NLRP3/IL1ß inflammasome associated with the aging bladder triggers bladder dysfunction in female rats.

Bladder dysfunction is associated with fibrosis­-mediated aging, but the corresponding mechanism remains to be elucidated. Activation of the NACHT, LRR and PYD domains­containing protein 3 (NLRP3) inflammasome is related to chronic diseases associated with aging, including organ fibrosis. The present study aimed to explore the role of NLRP3/interleukin 1ß in aging­associated bladder dysfunction. Female Sprague­Dawley rats were divided into the following two groups (n=10 rats/group): 2­month­old group (young group) and 24­month­old group (old group). Urodynamics were performed to assess the bladder function of the rats. The histological alterations were identified using Masson's trichrome staining. The protein expression of the NLRP3 inflammasome and NAD­dependent protein deacetylase sirtuin­3, mitochondrial (SIRT3) were detected by western blot analysis, and immunohistochemistry was used to examine a senescence marker (p21) and the NLRP3 inflammasome in the bladder. The localization of the key molecule Caspase1 was determined using immunofluorescence. The voiding time was longer in the old group compared with the young group. The expression levels of SIRT3 were reduced in the bladders of the old group, while those of the NLRP3 inflammasome and the senescence marker were significantly higher in the bladders of the old group compared with the young group. Increased collagen deposition leads to chronic bladder fibrosis with increased NLRP3. In the histological examination, the bladders of the old group displayed increased collagen deposition, urothelial thinning and detrusor shrinkage compared with the young group. Tissue fibrosis and urothelial alterations are the principal causes of bladder dysfunction during aging. Downregulated SIRT3 and upregulated expression of the NLRP3 inflammasome are involved in the degradation of aging bladders. Inflamm­aging is a novel mechanism underlying bladder dysfunction.

Drilling Combined with Adipose-derived Stem Cells and Bone Morphogenetic Protein-2 to Treat Femoral Head Epiphyseal Necrosis in Juvenile Rabbits.

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis, which can be done in juvenile rabbits. Passagefour bromodeoxyuridine (BrdU)-labeled ADSCs were cultured, assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability. Two-month-old, healthy male rabbits (1.2 to 1.4 kg, n=45) underwent ischemic induction and were randomly divided into five groups (group A: animal model control; group B: drilling; group C: drilling & ADSCs; group D: drilling & BMP-2; and group E: drilling & ADSCs & BMP-2). Magnetic resonance imaging (MRI), X-ray imaging, hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4, 6 and 10 weeks after treatment. Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability. Similar results were observed in the rabbits in groups C and E at weeks 6 and 10. The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P<0.01). Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P<0.05). In summary, drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis.

Spinal cord injury (SCI) is a severe traumatic lesion of central nervous system (CNS) with only a limited number of restorative therapeutic options. Diosgenin glucoside (DG), a major bioactive ingredient of Trillium tschonoskii Max., possesses neuroprotective effects through its antioxidant and anti-apoptotic functions. In this study, we investigated the therapeutic benefit and underlying mechanisms of DG treatment in SCI. We found that in Sprague-Dawley rats with traumatic SCI, the expressions of autophagy marker Light Chain 3 (LC3) and Beclin1 were decreased with concomitant accumulation of autophagy substrate protein p62 and ubiquitinated proteins, indicating an impaired autophagic activity. DG treatment, however, significantly attenuated p62 expression and upregulated the Rheb/mTOR signaling pathway (evidenced as Ras homolog enriched in brain) due to the downregulation of miR-155-3p. We also observed significantly less tissue injury and edema in the DG-treated group, leading to appreciable functional recovery compared to that of the control group. Overall, the observed neuroprotection afforded by DG treatment warrants further investigation on its therapeutic potential in SCI.

Enhanced biocompatibility and osseointegration of calcium titanate coating on titanium screws in rabbit femur.

This study aimed to examine the biocompatibility of calcium titanate (CaTiO3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO3 coating as an alternative to current implant coating materials. CaTiO3-coated titanium screws were implanted with hydroxyapatite (HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits. Imaging, histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation. Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO3 were fully regenerated and they were also well integrated with the screws. An interfacial fibrous membrane layer, which was found in the HA coating group, was not noticeable between the bone tissues and CaTiO3-coated screws. X-ray imaging analysis showed in the CaTiO3 coating group, there was a dense and tight binding between implants and the bone tissues; no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture. In contrast, uncoated screws exhibited a fibrous membrane layer, as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues. Additionally, biomechanical testing revealed that the binding strength of CaTiO3 coating with bone tissues was significantly higher than that of uncoated titanium screws, and was comparable to that of HA coating. The study demonstrated that CaTiO3 coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.

Bio-friendly Maillard reaction fluorescent products from glutathione and ascorbic acid for the rapid and label-free detection of Fe3+ in living cells.

Developing probes with good biocompatibility and realizing intracellular detection in living cells are of great significance for biomedicine and life sciences, but remain a challenge presently. In this paper, we describe a rapid and highly selective biosensor for Fe3+ detection in living cells based on the Maillard reaction fluorescent products (MRFPs) of glutathione and ascorbic acid as a probe. Experiments show that the MRFPs are non-cytotoxic and possess excellent biocompatibility. Moreover, the MRFPs show a rapid response and good selectivity towards Fe3+ over other metal ions under physiological pH conditions in vitro. The introduction of Fe3+ can quench the fluorescence of MRFPs, and the fluorescence intensity of system decreases linearly with the increasing concentration of Fe3+ in the range of 0.05-50 µM with the detection limit of 4.6 nM at a signal-to-noise ratio of 3. Moreover, the recognition mechanism has been discussed, which is attributed to the charge transfer from excited-state MRFPs molecules to metal ions. In addition, the MRFPs have been successfully demonstrated to be a good imaging probe for Fe3+ sensing in living cells. This study shows that the biocompatible MRFPs might hold great potential for applications in bioimaging, diagnosis, and therapy of intracellular diseases.

Novel targeting of PEGylated liposomes for codelivery of TGF-ß1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study.

Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-ß1 (TGF-ß1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-ß1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-ß1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 µg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 µg/mL. In addition, the TGF-ß1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical signaling pathways were eukaryotic initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of epithelial adherens junctions, epithelial adherens junction signaling, and Rho GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic targeting liposomes represent a promising delivery system for anti-TB drugs to human macrophages with good selectivity and minimal cytotoxicity.