Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

TiO2@COF Nanowire Arrays: A "Filter Amplifier" Heterojunction Strategy to Reverse the Redox Nature.

Surface modification is a promising method to change the surface properties of nanomaterials, but it is limited in enhancing their intrinsic redox nature. In this work, a "filter amplifier" strategy is proposed for the first time to reverse the intrinsic redox nature of materials. This is demonstrated by coating a COF-316 layer with controlled thickness on TiO2 to form core-sheath nanowire arrays. This unique structure forms a Z-scheme heterojunction to function as "a filter amplifier" which can conceal the intrinsic oxidative sites and increase the extrinsic reductive sites. Consequently, the selective response of TiO2 is dramatically reversed from reductive ethanol and methanol to oxidative NO2. Moreover, TiO2@COF-316 provides remarkably improved sensitivity, response, and recovery speed, as well as unusual anti-humidity properties as compared with TiO2. This work not only provides a new strategy to rationally modulate the surface chemistry properties of nanomaterials but also opens an avenue to design high-performance electronic devices with a Z-scheme heterojunction.

A study on the application of diffuse axonal multi-axis general evaluation for brain injury assessment in small overlap barrier crash test.

PURPOSE: Head injury criterion (HIC) companied by a rotation-based metric was widely believed to be helpful for head injury prediction in road traffic accidents. Recently, the Euro-New Car Assessment Program utilized a newly developed metric called diffuse axonal multi-axis general evaluation (DAMAGE) to explain test device for human occupant restraint (THOR) head injury, which demonstrated excellent ability in capturing concussions and diffuse axonal injuries. However, there is still a lack of comprehensive understanding regarding the effectiveness of using DAMAGE for Hybrid Ⅲ 50th percentile male dummy (H50th) head injury assessment. The objective of this study is to determine whether the DAMAGE could capture the risk of H50th brain injury during small overlap barrier tests. METHODS: To achieve this objective, a total of 24 vehicle crash loading curves were collected as input data for the multi-body simulation. Two commercially available mathematical dynamic models, namely H50th and THOR, were utilized to investigate the differences in head injury response. Subsequently, a decision method known as simple additive weighting was employed to establish a comprehensive brain injury metric by incorporating the weighted HIC and either DAMAGE or brain injury criterion. Furthermore, 35 sets of vehicle crash test data were used to analyze these brain injury metrics. RESULTS: The rotational displacement of the THOR head is significantly greater than that of the H50th head. The maximum linear and rotational head accelerations experienced by H50th and THOR models were (544.6 ± 341.7) m/s2, (2468.2 ± 1309.4) rad/s2 and (715.2 ± 332.8) m/s2, (3778.7 ± 1660.6) rad/s2, respectively. Under the same loading condition during small overlap barrier (SOB) tests, THOR exhibits a higher risk of head injury compared to the H50th model. It was observed that the overall head injury response during the small overlap left test condition is greater than that during the small overlap right test. Additionally, an equation was formulated to establish the necessary relationship between the DAMAGE values of THOR and H50th. CONCLUSION: If H50th rather than THOR is employed as an evaluation tool in SOB crash tests, newly designed vehicles are more likely to achieve superior performance scores. According to the current injury curve for DAMAGE and brain injury criterion, it is highly recommended that HIC along with DAMAGE was prioritized for brain injury assessment in SOB tests.

[Effect and mechanism of Maxing Shigan Decoction on reducing inflammatory response in rats with cough variant asthma via TLR4/MyD88/NF-κB and p38 MAPK signaling pathways].

This study aims to investigate the effect and mechanism of Maxingshigan Decoction on inflammation in the rat model of cough variant asthma(CVA). The SPF-grade SD rats of 6-8 weeks were randomized into normal, model, Montelukast sodium, and low-, medium-, and high-dose Maxing Shigan Decoction groups, with 8 rats in each group. The CVA rat model was induced by ovalbumin(OVA) and aluminum hydroxide sensitization and ovalbumin stimulation. The normal group and model group were administrated with equal volume of normal saline by gavage, and other groups with corresponding drugs by gavage. After the experiment, the number of white blood cells in blood and the levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α) in the serum were measured. The lung tissue was stained with hematoxylin-eosin(HE). Western blot was employed to determine the protein levels of nuclear factor-κB(NF-κB), Toll-like receptor 4(TLR4), myeloid differentiation protein(MyD88), and mitogen-activated protein kinase(MAPK) in the lung tissue. Real-time PCR was carried out to measure the mRNA levels of TLR4 and MyD88 in the lung tissue. Compared with the normal group, the model group showed increased white blood cells, elevated IL-6 and TNF-α levels(P<0.01), lowered IL-10 level(P<0.01), up-regulated protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK(P<0.01) and mRNA levels of TLR4 and MyD88(P<0.01) in the lung tissue. HE staining showed obvious infiltration of inflammatory cells around the airway and cell disarrangement in the model group. Compared with the model group, Montelukast sodium and high-dose Maxing Shigan Decoction reduced the white blood cells, lowered the IL-6 and TNF-α levels(P<0.01), and elevated the IL-10 level(P<0.01). Moreover, they down-regulated the protein levels of TLR4, MyD88, p-p65/NF-κB p65, p-p38 MAPK/p38 MAPK in the lung tissue(P<0.01) and the mRNA levels of TLR4 and MyD88 in the lung tissue(P<0.01). HE staining showed that Montelukast sodium and high-dose Maxing Shigan Decoction reduced inflammatory cell infiltration and cell disarrangement. The number of white blood cells, the levels of IL-10 and TNF-α in the serum, the protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK, and the mRNA levels of TLR4 and MyD88 in the lung tissue showed no significant differences between the Montelukast sodium group and high-dose Maxing Shigan Decoction group. Maxing Shigan Decoction can inhibit airway inflammation in CVA rats by inhibiting the activation of TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.

Surface Engineering in Covalent Organic Polymers for High-Performance Li-S Batteries.

Lithium-sulfur (Li-S) batteries are a promising energy storage technology due to their tempting high theoretical capacity and energy density. Nevertheless, the wastage of active materials that originates from the shuttling effect of polysulfides still hinders advancement of Li-S batteries. The effective design of cathode materials is extremely pivotal to solve this thorny problem. Herein, surface engineering in covalent organic polymers (COPs) has been performed to investigate the influence of pore wall polarity on the performance of COP-based cathodes used for Li-S batteries. With the assistance of experimental investigation and theoretical calculations, performance improvement by increasing pore surface polarity and a synergy effect of the polarized functionalities, along with nano-confinement effect of the COPs, are disclosed, to which the improved performance of Li-S batteries including outstanding Coulombic efficiency (99.0 %) and extremely low capacity decay (0.08 % over 425 cycles at 1.0 C) is attributed. This work not only enlightens the designable synthesis and applications of covalent polymers as polar sulfur hosts with high utilization of active materials, but also provides a feasible guide for the design of effective cathode materials for future advanced Li-S batteries.

In Situ Probing of the Surface Properties of Droplets in the Air.

Surface properties of nanodroplets and microdroplets are intertwined with their immense applicability in biology, medicine, production, catalysis, the environment, and the atmosphere. However, many means for analyzing droplets and their surfaces are destructive, non-interface-specific, not conducted under ambient conditions, require sample substrates, conducted ex situ, or a combination thereof. For these reasons, a technique for surface-selective in situ analyses under any condition is necessary. This feature article presents recent developments in second-order nonlinear optical scattering techniques for the in situ interfacial analysis of aerosol droplets in the air. First, we describe the abundant utilization of such droplets across industries and how their unique surface properties lead to their ubiquitous usage. Then, we describe the fundamental properties of droplets and their surfaces followed by common methods for their study. We next describe the fundamental principles of sum-frequency generation (SFG) spectroscopy, the Langmuir adsorption model, and how they are used together to describe adsorption processes at planar liquid and droplet surfaces. We also discuss the history of developments of second-order scattering from droplets suspended in dispersive media and introduce second-harmonic scattering (SHS) and sum-frequency scattering (SFS) spectroscopies. We then go on to outline the developments of SHS, electronic sum-frequency scattering (ESFS), and vibrational sum-frequency scattering (VSFS) from droplets in the air and discuss the fundamental insights about droplet surfaces that the techniques have provided. Finally, we describe some of the areas of nonlinear scattering from airborne droplets which need improvement as well as potential future directions and utilizations of SHS, ESFS, and VSFS throughout environmental systems, interfacial chemistry, and fundamental physics. The goal of this feature article is to spread knowledge about droplets and their unique surface properties as well as introduce second-order nonlinear scattering to a broad audience who may be unaware of recent progress and advancements in their applicability.

Electric double layer contribution to sum frequency generation signal from Au electrode.

Understanding the electric double layer (EDL) of the metal electrode-electrolyte interface is essential to electrochemistry and relevant disciplines. In this study, potential-dependent electrode Sum Frequency Generation (SFG) intensities of polycrystalline gold electrodes in HClO4 and H2SO4 electrolytes were thoroughly analyzed. The potential of zero charges (PZC) of the electrodes was -0.06 and 0.38 V in HClO4 and H2SO4, respectively, determined from differential capacity curves. Without specific adsorption, the total SFG intensity was dominated by the contribution from the Au surface and increased similar to that of the visible (VIS) wavelength scanning, which pushed the SFG process closer to the double resonant condition in HClO4. However, the EDL contributed about 30% SFG signal with specific adsorption in H2SO4. Below PZC, the total SFG intensity was dominated by the Au surface contribution and increased with potential at a similar slope in these two electrolytes. Around PZC, as the EDL structure became less ordered and the electric field changed direction, there would be no EDL SFG contribution. Above PZC, the total SFG intensity increased much more rapidly with potential in H2SO4 than in HClO4, which suggested that the EDL SFG contribution kept increasing with more specific adsorbed surface ions from H2SO4.

[Huazhi Rougan Granules attenuates steatosis in cell model of nonalcoholic fatty liver disease by inducing autophagy].

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.

Directional Defect Management in Perovskites by In Situ Decomposition of Organic Metal Chalcogenides for Efficient Solar Cells.

Directional defects management in polycrystalline perovskite film with inorganic passivator is highly demanded while yet realized for fabricating efficient and stable perovskite solar cells (PSCs). Here, we develop a directional passivation strategy employing a two-dimensional (2D) material, Cu-(4-mercaptophenol) (Cu-HBT), as a passivator precursor. Cu-HBT combines the merits of the targeted modification from organic passivator and excellent stability offered by inorganic passivator. Featuring with dense organic functional motifs on its surfaces, Cu-HBT has the capability to "find" and fasten to the Pb defect sites in perovskites through coordination interactions during a spin-coating process. During subsequent annealing treatment, the organic functional motifs cleave from Cu-HBT and convert in situ into p-type semiconductors, Cu2 S and PbS. The resultant Cu2 S and PbS not only serve as stable inorganic passivators on the perovskite surface, significantly enhancing cell stability, but also facilitate efficient charge extraction and transport, resulting in an impressive efficiency of up to 23.5 %. This work contributes a new defect management strategy by directionally yielding the stable inorganic passivators for highly efficient and stable PSCs.

A Humidity-Induced Large Electronic Conductivity Change of 107 on a Metal-Organic Framework for Highly Sensitive Water Detection.

The electronic conductivity (EC) of metal-organic frameworks (MOFs) is sensitive to strongly oxidizing guest molecules. Water is a relatively mild species, however, the effect of H2 O on the EC of MOFs is rarely reported. We explored the effect of H2 O on the EC in the MOFs (NH2 )2 -MIL-125 and its derivatives with experimental and theoretical investigations. Unexpectedly, a large EC increase of 107 on H2 SO4 @(NH2 )2 -MIL-125 by H2 O was observed. Brønsted acid-base pairs formed with the -NH2 groups, and H2 SO4 played an important role in promoting the charge transfer from H2 O to the MOF. Based on H2 SO4 @(NH2 )2 -MIL-125, a high-performance chemiresistive humidity sensor was developed with the highest sensitivity, broadest detection range, and lowest limit of detection amongst all reported sensing materials to date. This work not only demonstrated that H2 O can remarkably influence the EC of MOFs, but it also revealed that post-modification of the structure of MOFs could enhance the influence of the guest molecule on their EC to design high-performance sensing materials.

The phycobilisome core-membrane linkers from Synechocystis sp. PCC 6803 and red-algae assemble in the same topology.

The phycobilisomes (PBSs) of cyanobacteria and red-algae are unique megadaltons light-harvesting protein-pigment complexes that utilize bilin derivatives for light absorption and energy transfer. Recently, the high-resolution molecular structures of red-algal PBSs revealed how the multi-domain core-membrane linker (LCM ) specifically organizes the allophycocyanin subunits in the PBS's core. But, the topology of LCM in these structures was different than that suggested for cyanobacterial PBSs based on lower-resolution structures. Particularly, the model for cyanobacteria assumed that the Arm2 domain of LCM connects the two basal allophycocyanin cylinders, whereas the red-algal PBS structures revealed that Arm2 is partly buried in the core of one basal cylinder and connects it to the top cylinder. Here, we show by biochemical analysis of mutations in the apcE gene that encodes LCM , that the cyanobacterial and red-algal LCM topologies are actually the same. We found that removing the top cylinder linker domain in LCM splits the PBS core longitudinally into two separate basal cylinders. Deleting either all or part of the helix-loop-helix domain at the N-terminal end of Arm2, disassembled the basal cylinders and resulted in degradation of the part containing the terminal emitter, ApcD. Deleting the following 30 amino-acids loop severely affected the assembly of the basal cylinders, but further deletion of the amino-acids at the C-terminal half of Arm2 had only minor effects on this assembly. Altogether, the biochemical data are consistent with the red-algal LCM topology, suggesting that the PBS cores in cyanobacteria and red-algae assemble in the same way.

Evolution of the CBL and CIPK gene families in Medicago: genome-wide characterization, pervasive duplication, and expression pattern under salt and drought stress.

BACKGROUND: Calcineurin B-like proteins (CBLs) are ubiquitous Ca2+ sensors that mediate plant responses to various stress and developmental processes by interacting with CBL-interacting protein kinases (CIPKs). CBLs and CIPKs play essential roles in acclimatization of crop plants. However, evolution of these two gene families in the genus Medicago is poorly understood. RESULTS: A total of 68 CBL and 135 CIPK genes have been identified in five genomes from Medicago. Among these genomes, the gene number of CBLs and CIPKs shows no significant difference at the haploid genome level. Phylogenetic and comprehensive characteristic analyses reveal that CBLs and CIPKs are classified into four clades respectively, which is validated by distribution of conserved motifs. The synteny analysis indicates that the whole genome duplication events (WGDs) have contributed to the expansion of both families. Expression analysis demonstrates that two MsCBLs and three MsCIPKs are specifically expressed in roots, mature leaves, developing flowers and nitrogen fixing nodules of Medicago sativa spp. sativa, the widely grown tetraploid species. In particular, the expression of these five genes was highly up-regulated in roots when exposed to salt and drought stress, indicating crucial roles in stress responses. CONCLUSIONS: Our study leads to a comprehensive understanding of evolution of CBL and CIPK gene families in Medicago, but also provides a rich resource to further address the functions of CBL-CIPK complexes in cultivated species and their closely related wild relatives.

The role of histone chaperone spty2d1 in human colorectal cancer.

Colorectal cancer (CRC) remains a major public health concern, associated with a high rate of morbidity and mortality. Several factors have been implicated in its occurrence and development, which includes histone chaperones. The role of spty2d1 (spt2)-a novel histone chaperone protein-has rarely been investigated in CRC. Therefore, we demonstrated in this study that spt2 undergoes different genetic alterations in colorectal adenocarcinoma datasets and that it was associated with the proliferation of colon carcinoma. Spt2 silencing can reduce the ability of proliferation and increase the rate of apoptosis of LoVo cells. Regarding the overall survival associated with spt2, only the quartile disease-free survival of colon adenocarcinoma (COAD) was found to be statistically significant, while that of rectum adenocarcinoma (READ) was not. The positive (+++) expression of spt2 was correlated with a deeper invasion depth in colorectal adenocarcinoma, and this effect was more pronounced in COAD. These data collectively suggest that spt2 can influence the progression and prognosis in some subtypes of colorectal adenocarcinoma. Therefore, we propose spt2 as a potential target for application in enhancing the overall therapeutic efficacy in some specific subtypes of colorectal adenocarcinoma.

In Situ Detection of Chemical Compositions at Nanodroplet Surfaces and In-Nanodroplet Phases.

Small-volume nanodroplets play an increasingly common role in chemistry and biology. Such nanodroplets are believed to have unique chemical and physical properties at the interface between a droplet and its surrounding medium, however, they are underexamined. In this study, we present the novel technique of vibrational sum frequency scattering (VSFS) spectroscopy as an interface-specific, high-performance method for the in situ investigation of nanodroplets with sub-micron radii; as well as the droplet bulk through simultaneous hyper-Raman scattering (HRS) spectroscopy. We use laboratory-generated nanodroplets from aqueous alcohol solutions to demonstrate this technique's ability to separate the vibrational phenomena which take place at droplet surfaces from the underlying bulk phase. In addition, we systemically examine interfacial spectra of nanodroplets containing methanol, ethanol, 1-propanol, and 1-butanol through VSFS. Furthermore, we demonstrate interfacial differences between such nanodroplets and their analogous planar surfaces. The sensitivity of this technique to probe droplet surfaces with few-particle density at standard conditions validates VSFS as an analytical technique for the in situ investigation of small nanodroplets, providing breakthrough information about these species of ever-increasing relevance.

Connexin 43 hyper-phosphorylation at serine 282 triggers apoptosis in rat cardiomyocytes via activation of mitochondrial apoptotic pathway.

Cx43 is the major connexin in ventricular gap junctions, and plays a pivotal role in control of electrical and metabolic communication among adjacent cardiomyocytes. We previously found that Cx43 dephosphorylation at serine 282 (pS282) caused cardiomyocyte apoptosis, which is involved in cardiac ischemia/reperfusion injury. In this study we investigated whether Cx43-S282 hyper-phosphorylation could protect cardiomyocytes against apoptosis. Adenovirus carrying rat full length Cx43 gene (Cx43-wt) or a mutant gene at S282 substituted with aspartic acid (S282D) were transfected into neonatal rat ventricular myocytes (NRVMs) or injected into rat ventricular wall. Rat abdominal aorta constriction model (AAC) was used to assess Cx43-S282 phosphorylation status. We showed that Cx43 phosphorylation at S282 was increased over 2-times compared to Cx43-wt cells at 24 h after transfection, while pS262 and pS368 were unaltered. S282D-transfected cells displayed enhanced gap junctional communication, and increased basal intracellular Ca2+ concentration and spontaneous Ca2+ transients compared to Cx43-wt cells. However, spontaneous apoptosis appeared in NRVMs transfected with S282D for 34 h. Rat ventricular myocardium transfected with S282D in vivo also exhibited apoptotic responses, including increased Bax/Bcl-xL ratio, cytochrome c release as well as caspase-3 and caspase-9 activities, while factor-associated suicide (Fas)/Fas-associated death domain expression and caspase-8 activity remained unaltered. In addition, AAC-induced hypertrophic ventricles had apoptotic injury with Cx43-S282 hyper-phosphorylation compared with Sham ventricles. In conclusion, Cx43 hyper-phosphorylation at S282, as dephosphorylation, also triggers cardiomyocyte apoptosis, but through activation of mitochondrial apoptosis pathway, providing a fine-tuned Cx43-S282 phosphorylation range required for the maintenance of cardiomyocyte function and survival.

Biomechanical behaviour of implant prostheses and adjacent teeth according to bone quality: A finite element analysis.

The contribution of biomechanical factors in the formation of proximal contact loss has been observed, but there is little research on the mechanisms by which they contribute. Using finite element analysis, this study aimed to analyse the impact of bone quality on the biomechanical behaviour of a dentition consisting of implant prostheses and adjacent teeth. The occlusal load was applied on the implant/tooth crown. In the mesiodistal direction, the adjacent natural tooth mesially to the implant denture had the tendency for mesial movement, while the distal adjacent natural tooth had the tendency for distal movement. For the supporting bone around the mesial adjacent tooth, the maximum/minimum principal stress and strain values on the mesial side of the bone were higher than those on the distal side of the bone. Stress and strain values on the mesial side of the supporting bone around the distal adjacent tooth were lower than those on the distal side. With decreasing bone density, displacements of teeth and the implant denture, principal stresses and equivalent strains on tooth supporting bone increased. Studies on biomechanical behaviours of a tooth-implant dentition may provide a deeper understanding of implant-induced dental adaptive processes such as proximal contact loss.

Exposure to perchlorate, nitrate and thiocyanate was associated with the prevalence of cardiovascular diseases.

AIMS: To determine the association between urinary levels of perchlorate, nitrate and thiocyanate, and the prevalence of cardiovascular diseases (CVD) among general population. METHODS: A total of 16, 570 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). Urinary levels of perchlorate, nitrate and thiocyanate were measured using ion chromatography coupled with electrospray tandem mass spectrometry. Multivariable linear regressions and logistic regressions were performed to explore the associations of exposure to perchlorate, nitrate and thiocyanate, and the prevalence of total and specific CVD, including chronic heart failure (CHF), coronary heart disease (CHD), angina, heart failure and stroke. Restricted cubic splines were used to explore the nonlinearity. RESULTS: Participants with CVD had a lower urinary level of nitrate and thiocyanate (all P < 0.001). A null association between urinary perchlorate and total CVD or specific CVD was observed. Comparing with the lowest quartile, the highest quartile of urinary nitrate was independently associated with a decreased presence of total CVD (odds ratio [OR] 0.66, 95% confidence interval [CI] [0.53, 0.82]), CHF (OR 0.48, 95% CI [0.33, 0.71]), and stroke (OR 0.63, 95%CI [0.45, 0.88]). In addition, per one-fold increasement of urinary nitrate decreased a 0.15-fold prevalence of total CVD, 0.29-fold prevalence of CHF, and 0.16-fold prevalence of stroke. However, for urinary thiocyanate, we found that the 2nd and 3rd quartile were associated with total CVD, the 2nd quartile associated with heart attack, and the 2nd, 3rd and 4th quartile associated with stroke. What's more, restricted cubic splines confirmed that the relation between urinary nitrate and CVD was linear (P for nonlinearity = 0.242) and the inverse relation between urinary thiocyanate and CVD was nonlinear (P for nonlinearity < 0.001). CONCLUSION: In the general population, low levels of nitrate were linearly while thiocyanate were nonlinearly associated with an increased presence of cardiovascular diseases.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization.

BACKGROUND: Polydatin, a glucoside of resveratrol, has been shown to have protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. METHODS: After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. RESULTS: Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1ß, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. CONCLUSIONS: Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.

Perceived uncertainty stress and its predictors among residents in China during the COVID-19 pandemic.

The prevalence of and risk factors for uncertainty stress among residents during the COVID-19 pandemic remain unclear. An online cross-sectional survey was conducted to explore and identify the risk factors for high perceived uncertainty stress among the general public in China during the COVID-19 outbreak. Information about the respondents' socioeconomic characteristics, knowledge of and attitudes towards COVID-19, perceived uncertainty stress, social capital, anxiety, and depressive symptoms was collected and analysed. Among the 1205 respondents, 45.3% (546) reported a high level of uncertainty stress. Multiple linear regression analysis indicated that anxiety (ß=3.871,P<0.001) and depression symptoms (ß=2.458, P<0.001), family residence (in towns or rural areas) (ß=0.947, P<0.001), lack of support for local epidemic control strategies (ß=1.253, P<0.001), worry about the pandemic (ß=1.191, P<0.001), and symptoms of weakness among family members (ß=1.525, P=0.002) were positively associated with perceived uncertainty stress. Cognitive social capital (ß=-0.883, P<0.001) and social networks (ß=-0.726, P<0.001) were negatively, but social participation (ß=0.714, P<0.001) was positively associated with perceived uncertainty stress. Our findings identify factors associated with a higher level of uncertainty stress and should be helpful in the consideration of effective policies and interventions for uncertainty stress during the initial phases of public health emergencies.

The Growth Mechanism of a Conductive MOF Thin Film in Spray-based Layer-by-layer Liquid Phase Epitaxy.

The layer-by-layer liquid-phase epitaxy (LBL-LPE) method is widely used in preparing metal-organic framework (MOF) thin films with the merits of controlling thickness and out-of-plane orientation for superior performances in applications. The LBL-LPE growth mechanism related to the grain boundary, structure defect, and orientation is critical but very challenging to study. In this work, a novel "in-plane self-limiting and self-repairing" thin-film growth mechanism is demonstrated by the combination study of the grain boundary, structure defect, and orientation of Cu3 (HHTP)2 -xC thin film via microscopic analysis techniques and electrical measurements. This mechanism results a desired high-quality MOF thin film with preferred in-plane orientations at its bottom for the first time and is very helpful for optimizing the LBL-LPE method, understanding the growth cycle-dependent properties of MOF thin film, and inspiring the investigations of the biomimetic self-repairing materials.