Rutaecarpine ameliorates imiquimod-induced psoriasis-like dermatitis in mice associated with alterations in the gut microbiota.

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.

Heterochiral π-stacking dimerization of helical secondary structures with emerging supramolecular chirality.

In this work, we report a new type of interface modes between helical secondary structures by noncovalent assembly along the helical axis. The dimerization of helical secondary structures mediated by aromatic π-stacking leads to discrete heterochiral dimeric helical rods consisting of left-handed helix and right-handed helix, which has been demonstrated by single-crystal X-ray diffraction. We conduct chiral induction studies on discrete heterochiral dimers to regulate the preference of the helical sense. Surprisingly, we found a novel supramolecular chirality potentially occurring inside the super-secondary structure of chirality-induced heterochiral helical dimers, rather than the racemization of helical chirality. Furthermore, chirality-induced heterochiral helical dimers can exhibit unique chiral switches when formed or not formed. In order to identify the emerging supramolecular chirality of discrete heterochiral dimeric helix, we covalently synthesized meso-helix structures with opposite helical handedness. The chirality of aromatic chromophore linker was confirmed by chiral induction despite competition from opposite handed helices, which strongly demonstrates the occurrence of emerging supramolecular chirality in heterochiral dimeric helix. This study not only reports the heterochiral π-stacking dimerization of helical secondary structures for the first time, but also discovers novel supramolecular chirality hidden in the structure of noncovalent and even covalent meso-helices.

ER stress-related protein, CHOP, may serve as a biomarker of mechanical asphyxia: a primary study.

The precise authentication of death from mechanical asphyxia (DMA) has been a complex problem in forensic medicine. Besides the traditional methods that concern the superficial characterization of the body, researchers are now paying more attention to the biomarkers that may help the identification of DMA. It has been reported that the extremely hypoxic environment created by DMA can cause the specific expression of mitochondria-related protein, which may sever as the biomarkers of DMA authentication. Since endoplasmic reticulum stress (ER stress) has been found to be related to the dysfunction of mitochondria, it is promising to look for the biomarkers of DMA among ER stress-related proteins. In this article, animal and cell experiments were conducted to examine how ER-mitochondria interaction may be influenced in the hypoxic condition caused by DMA primarily. Human samples were then used to verify the possible biomarkers of DMA. We found that ER stress-related protein CHOP was significantly up-regulated within a short-term postmortem interval (PMI) in brain tissue of DMA samples, which may interact with a series of ER stress- and mitochondria-related protein, leading to the apoptosis of the cells. It was also verified in human samples that the expression level of CHOP can sever as a potential biomarker of DMA within a specific PMI.

A multifunctional DNA nanostructure based on multicolor FRET for nuclease activity assay.

Nucleases play a crucial role in DNA replication, recombination and repair which are associated with cancers. Herein, we develop a four-color fluorescent probe for ratiometric detection of multiple nucleases. This four-color fluorescent probe consists of four fluorescent dyes connected by a DNA tetrahedral nanostructure with the involvement of multistep fluorescence resonance energy transfer (FRET). Based on the principle of self-assembly, the four-color fluorescent probe is constructed by integrating one acceptor with three spatially and spectrally distinct acceptors. A DNA tetrahedral nanostructure functions as a scaffold to link the acceptor dyes (i.e., diethylaminocoumarin (DEA), carboxyfluorescein (FAM), Texas Red, and Cy5). The fluorescence emissions of DEA, FAM, Texas Red and Cy5 can be observed through efficient multi-step energy transfer. This four-color fluorescent probe enables single excitation/four emissions, and it can be used for ratiometric detection of nucleases (i.e., XhoI, HindIII and KpnI) and the screening of nuclease inhibitors. Importantly, this four-color fluorescent probe can be further applied to discriminate multiple biomolecule targets by simply integrating the recognition sites of various biomolecules into the DNA tetrahedral nanostructure.

Knockdown of circ-ABCB10 promotes sensitivity of lung cancer cells to cisplatin via miR-556-3p/AK4 axis.

BACKGROUND: Due to the acquired drug resistance, the potency of cisplatin-based chemotherapy is limited in lung cancer, which is a big obstacle in clinical treatment of lung cancer. Abundant evidence has revealed that circular RNAs (circRNAs) exerted facilitating or suppressive function on the tumorigenesis of multiple cancers. The oncogenic role of circ-ABCB10 in breast cancer and clear cell renal cell carcinoma has been validated in recent researches. However, the regulatory mechanism of circ-ABCB10 and its relation to cellular sensitivity to cisplatin in lung cancer is poorly understood. METHODS: The expression and characteristic of circ-ABCB10 were analyzed by RT-qPCR and nucleic acid electrophoresis. CCK-8, colony formation, TUNEL and transwell assays were applied to probe the role of FOXD3-AS1 in lung cancer. The interactions of miR-556-3p with circ-ABCB10 and AK4 were testified by luciferase reporter and RIP assays. RESULTS: Circ-ABCB10 was markedly upregulated and featured with loop structure in lung cancer. Circ-ABCB10 depletion suppresses lung cancer progression and sensitizes lung cancer cells to cisplatin. Molecular mechanism assays manifested that circ-ABCB10 bound with miR-556-3p and negatively modulated miR-556-3p expression. Additionally, AK4 was testified to be the downstream target of miR-556-3p. More importantly, rescue assays clarified that upregulation of AK4 could reverse the cisplatin-sensitizing and tumor-suppressing effect of circ-ABCB10 knockdown on lung cancer cells. CONCLUSIONS: Circ-ABCB10 knockdown enhances sensitivity of lung cancer cells to cisplatin by targeting miR-556-3p/AK4 axis.

Microdisk resonators with lithium-niobate film on silicon substrate.

In this paper, we report the fabrication of lithium niobate (LN) microdisk resonators on a pulsed-laser deposited polycrystalline LN film on a silicon substrate rather than commercially provide LN film on insulator. The quality factor of these polycrystalline LN microdisks were measured above 3.4×104 in the 1550-nm band. Second harmonic generation was demonstrated in the fabricated microresonators. Because the properties of homemade LN film can be easily tuned by doping various ions, LN devices on homemade LN film may have more flexible functions and broad applications.

Fucosyltransferase 2 induced epithelial-mesenchymal transition via TGF-ß/Smad signaling pathway in lung adenocarcinaoma.

Fucosyltransferase 2 (FUT2), the enzyme catalyzing α-1,2-fucosylation in mammals, has been implicated in cancer. The up-regulation of FUT2 has been observed in lung adenocarcinoma (LUAD), and FUT2 can enhance the cell migration and invasion of LUAD cell lines. However, the underlying mechanism of FUT2 in LUAD remains largely unknown. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during lung cancer metastasis and progression. In the present study, we showed that knocking down FUT2 in LUAD cell lines increased the expression of E-cadherin and reduced the expression of Vimentin, N-cadherin, TßRII, p-Smad2, p-Smad3 and Snail, which were the makers of EMT. Meanwhile, the expression of E-cadherin was decreased, and the expression of Vimentin was increased by restoring the expression of FUT2 in RNA interference FUT2 (RNAi-FUT2) cells, suggesting that FUT2 enhanced the EMT process in LUAD. Additionally, silencing FUT2 expression can up-regulate E-cadherin and down-regulate Vimentin, significantly attenuated EMT in vivo. Treated with the SIS3, a new-type inhibitor of p-Smad3 of TGF-ß signaling, the expression of E-cadherin, Vimentin and Snail were not affected by RNAi-FUT2 cells, indicating that the effect of FUT2 on EMT depended on TGF-ß/Smad signaling. Overall, the current results indicated that FUT2 might promote LUAD metastasis through the EMT initiated by TGF-ß/Smad signaling. Therefore, FUT2 might be a prognostic factor and therapeutic target for LUAD.

Curcumolide reduces diabetic retinal vascular leukostasis and leakage partly via inhibition of the p38MAPK/NF-κ B signaling.

Retinal inflammation in a hyperglycemic condition is believed to play a crucial role in the development of diabetic retinopathy, and targeting inflammatory mediators is a promising strategy for the control of diabetic retinopathy. Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. In this study, we demonstrate that treatment with curcumolide alleviated retinal inflammatory activities both in vitro and in vivo in a STZ-induced diabetic rat model and in TNF-α-stimulated HUVECs. Curcumolide alleviated retinal vascular permeability and leukostasis and attenuated the overexpression of TNF-α and ICAM-1 in diabetic retinas. Moreover, curcumolide also inhibited inducible p38 MAPK and NF-κB activation and the subsequent induction of proinflammatory mediators. These data suggest potential treatment strategies against diabetic retinopathy, particularly in the early stages of the disease.

Estimation of the human postmortem interval using an established rat mathematical model and multi-RNA markers.

In our previous study, a R code-based mathematical model using RNA degradation patterns was developed for PMI determination in rat brain specimens. However, the postmortem changes of RNA are much more complicated in real cases, and there is still a huge challenge in efficiently applying information in animal data to real cases. In the present study, different RNA markers in both rat and human tissues were collected to screen valid biomarkers and the corresponding mathematical models were established and validated. With the same methodology, multi-RNA markers of myocardium and liver tissues were detected by qPCR and the Ct values of ten biomarkers generally increased with prolonged PMIs. 5S, miR-1 and miR-133a were shown to be optimum reference biomarkers that were not affected by a PMI of up to 5 or more days; however, liver-specific miR-122 began to degrade under higher temperatures and only 5S was selected as an endogenous control in the liver. Among the tested target RNAs, similar to our previous study in brain tissue, ß-actin (ΔCt) was found to exhibit the best correlation coefficient with PMI and was employed to build mathematical models using R software. Following validation, the relatively low estimated error demonstrated that PMIs can be accurately predicted in human cases through comprehensive consideration of various factors and using effective biomarkers.

Epitome of China's unnatural deaths: a historically retrospective study of forensic autopsy cases in Shanghai Public Security Bureau from 1990 to 1999.

The unnatural death investigation in China seems vague to the world. Shanghai is one of the largest city located in Yangtze River Delta in the East China. This study is committed to lift the veil of unnatural death investigation and describe the epitome of China's unnatural deaths. Based on the 7302 forensic report archives from 1990 to 1999 in Shanghai Public Security Bureau, statistics were carried out in 5 areas according to the manner of death. In 3502 accidental deaths, there was a rapid increase during the 1990s, and 71.6% were involved in traffic accidents whose major cause of death was head and neck injuries. The first 3 causes of death in nontraffic accidents (994) were head and neck injuries (42.8%), poisoning (11.8%), and drowning (9.0%). In 2456 homicides, sharp force injury (36.7%), blunt force injury (35.8%), and manual strangulation (12.9%) were the first 3 causes of death. In 563 suicides, drug/chemical intoxication (40.1%), hanging (23.4%), and injuries because of fall from height (11.4%) were the 3 leading causes of death, especially pesticides ingestion. The causes of natural deaths were diseases mainly in circulatory system (23.1%), central nervous system (12.8%), and respiratory system (6.4%). However, the cause of death remained undetermined in 500 victims. Childhood fatalities were different. The victims of accidents and homicides were nearly equal, and the main cause of homicide was manual strangulation. Besides, 1997 was the landmark year when drug abuse began to emerge in Shanghai.

Postmortem interval determination using 18S-rRNA and microRNA.

The importance of determining postmortem interval (PMI) is crucial to criminal, civil and forensic cases. The precise estimation of PMI is a critical step in many death investigations. A technique exploiting the level of RNA, 18S rRNA and microRNA to estimate PMI was investigated. 18S-rRNA is a main ribosomal RNA presented as part of the ribosomal protein complex, while microRNA is a class of small non-coding single-stranded RNA, only 21-25 nucleotides, which has a strong conservation between different species. In this study, heart tissues were removed from adult rats at various postmortem intervals. An efficient extraction and detection protocol to analyze the level of 18S-rRNA and microRNA in postmortem tissue was carried out. The process consists of total RNA extraction, transcription and visualization by quantitative real time PCR. The result indicates a characteristic parabola relationship between postmortem period and Ct values for 18S-rRNA in dead rat hearts. The result indicates that the degradation pattern of tissue 18S-rRNA and microRNA is useful in the determination of the postmortem interval within seven days.

[Relationship between PMI and relative expression of myocardial various RNAs in rats died of different causes].

OBJECTIVE: To observe the changes of relative expression of myocardial various RNAs in rats died of different causes and their relationship with PMI. METHODS: The rat models were established in which the rats were sacrificed by broken neck, asphyxia, and hemorrhagic shock. Total RNAs were extracted from myocardium. The quantitative real time PCR was used to calculate threshold cycle values of RNAs including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, inducible nitric oxide synthase (iNOS), hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and U6 small nuclear RNA (U6 snRNA) and to study the changes of the relative expressions of various indexes with PMI. RESULTS: U6 snRNA with stable expression level could be used as appropriate internal control. In the early PMI, the relative expression of GAPDH, HIF-1, iNOS, TNF-alpha, and IL-6 more characteristically increased in groups of asphyxia and hemorrhagic shock than in group of broken neck, but the quantity of beta-actin decreased in all groups. In the late PMI, all the relative expressions significantly declined in correlation with the degradation of RNA. CONCLUSION: The characteristic changes of each RNA expression can be used as references to estimate PMI in deaths by different causes.

Effective adsorption of As(V) from aqueous solution by quaternary ammonium and Zn2+ decorated lignin-based sorbent.

Arsenic poses a serious harm to the natural environment and human health. Lignin decorated with quaternary ammonium and metal ion can effectively adsorb arsenic from aqueous solution. Zn2+/quaternary ammonium lignin was synthesized by quaternization and metallization from lignin with 3-Chloro-2-hydroxypropyl trimethylammonium chloride and ZnCl2. The morphology, functional groups and chemical compositions of adsorbent were identified by SEM-EDS, FTIR and XRD. The effects such as pH, initial As(V) concentration, contact time and adsorbent dosage on the adsorption capacity were investigated in batch system. The adsorption mechanism was explored by SEM-EDS, FTIR and XPS. It was shown that the adsorbent was rough and contained a large amount of quaternary ammonium and Zn2+. Zn2+/quaternary ammonium lignin exhibited much strong affinity towards As(V) with the maximum adsorption capacity of 70.38 mg·g-1 at 25 °C, oscillation rate of 180 r·min-1, pH of 5, initial As(V) concentration of 100 mg·L-1, contact time of 30 min and 1 g·L-1 Zn2+/quaternary ammonium lignin. The adsorption could be well described by Langmuir model and quasi-second-order kinetic model, indicating the monolayer homogeneous chemisorption nature. As(V) was adsorbed through electrostatic attraction of Zn2+ and ion exchange between H2AsO4- and Cl-.

Adverse reactions caused by high serum concentration of linezolid: Two case reports and literature review.

Linezolid is a potent oxazolidinone for the treatment of various gram-positive bacterial infections. However, the drug can cause potential adverse reactions such as thrombocytopenia, hyperlactacidemia and serotonin syndrome, which warrant consideration by the medical team when planning treatment. The existing literature has reported some adverse reactions caused by linezolid, but most of these are based on clinical characteristics and simple treatment measures. Two cases of linezolid overdose resulting in thrombocytopenia, hyperlactacidemia and serotonin syndrome are presented, which were successfully managed with therapeutic drug monitoring. A dose adjustment strategy was adopted to safely and effectively mitigate linezolid-related adverse events.

The signaling pathways of selected traditional Chinese medicine prescriptions and their metabolites in the treatment of diabetic cardiomyopathy: a review.

Diabetic cardiomyopathy (DCM) is a myocardial-specific microvascular disease caused by diabetes that affects the structure and function of the heart and is considered to be the leading cause of morbidity and death in patients with diabetes. Currently, there is no specific treatment or preventive drug for DCM, and there is an urgent need to develop new drugs to treat DCM. Traditional Chinese medicine (TCM) has rich experience in the treatment of DCM, and its characteristics of multi-target, multi-pathway, multi-component, and few side effects can effectively deal with the complexity and long-term nature of DCM. Growing evidence suggests that myocardial fibrosis, inflammation, oxidative stress, apoptosis, cardiac hypertrophy, and advanced glycation end product deposition were the main pathologic mechanisms of DCM. According to the pathological mechanism of DCM, this study revealed the potential of metabolites and prescriptions in TCM against DCM from the perspective of signaling pathways. The results showed that TGF-ß/Smad, NF-κB, PI3K/AKT, Nrf2, AMPK, NLRP3, and Wnt/ß-catenin signaling pathways were the key signaling pathways for TCM treatment of DCM. The aim of this study was to summarize and update the signaling pathways for TCM treatment of DCM, to screen potential targets for drug candidates against DCM, and to provide new ideas and more experimental evidence for the clinical use of TCM treatment of DCM.

Single-Stranded Nucleic Acid Transmembrane Molecular Carriers Based on Positively Charged Helical Foldamers.

Transmembrane delivery of biologically active nucleic acids is an important process in cells and has inspired one to develop advanced drug delivery techniques. In this contribution, molecular-level single-stranded nucleic acid transmembrane carriers are reported based on 3.2 nm long Huc's foldamers (AOrnQ3Q3)8 and (mQ3Q2)8 with linearly and helically aligned positive charges, respectively. These two foldamers not only show very strong DNA affinity via electrostatic interactions but also discriminatively bind single-stranded DNA (ss-DNA) and double-stranded DNA (ds-DNA), corroborating the importance of precise charge arrangement in the electrostatic interactions. More importantly, these two foldamers are capable of efficiently transporting ss-DNA across the lipid membranes, and the ss-DNA transport activity of (AOrnQ3Q3)8 with linearly aligned charges is higher than that of (mQ3Q2)8 with helically aligned charges. Thus a type of novel single-stranded nucleic acid transmembrane molecular carriers based on positively charged helical foldamers are introduced. Further, effective and enhanced expression in EGFP-mRNA transfection experiments strongly demonstrates the potential of positively charged foldamers for RNA transmembrane transport and therapy.

Versatile photonic molecule switch in multimode microresonators.

Harnessing optical supermode interaction to construct artificial photonic molecules has uncovered a series of fundamental optical phenomena analogous to atomic physics. Previously, the distinct energy levels and interactions in such two-level systems were provided by coupled microresonators. The reconfigurability is limited, as they often require delicate external field stimuli or mechanically altering the geometric factors. These highly specific approaches also limit potential applications. Here, we propose a versatile on-chip photonic molecule in a multimode microring, utilizing a flexible regulation methodology to dynamically control the existence and interaction strength of spatial modes. The transition between single/multi-mode states enables the "switched-off/on" functionality of the photonic molecule, supporting wider generalized applications scenarios. In particular, "switched-on" state shows flexible and multidimensional mode splitting control in aspects of both coupling strength and phase difference, equivalent to the a.c. and d.c. Stark effect. "Switched-off" state allows for perfect low-loss single-mode transition (Qi ~ 10 million) under an ultra-compact bend size (FSR ~ 115 GHz) in a foundry-based silicon microring. It breaks the stereotyped image of the FSR-Q factor trade-off, enabling ultra-wideband and high-resolution millimeter-wave photonic operations. Our demonstration provides a flexible and portable solution for the integrated photonic molecule system, extending its research scope from fundamental physics to real-world applications such as nonlinear optical signal processing and sixth-generation wireless communication.

8-oxoguanine DNA glycosylase-1 may serve as biomarker of mechanical asphyxia.

AIM: To identify mtDNA and OGG1 as potential biomarker candidates for mechanical asphyxia. METHOD: The human tissues are divided into experimental group (hanging and strangulation) and control groups (hemorrhagic shock, brain injury group, and poisoning group). Detected the expression of OGG1 and integrity of mtDNA in cardiac tissue of each group. We used over-OGG1 vector and siRNA-OGG1 transfecting H9C2 cell line to observe the function of OGG1 in hypoxic cells. RESULTS: 1. mtDNA integrity decreased in the mechanical asphyxia group, OGG1 expression increased in mechanical asphyxia groups. They can be biomarkers for mechanical asphyxia. 2. OGG1 increased first and decreased in hypoxia-induced H9C2 cells. OGG1 upregulated the TFAM, NRF1, and Bcl2 in hypoxia-induced H9C2. OGG1 downregulated cleaved-Caspase3 in hypoxia-induced H9C2 cells. 3. In the normoxia condition, NAC maintained mtDNA integrity and decreased the mitochondrial membrane potential and amount of ATP. CONCLUSION: mtDNA integrity and OGG1 expression can be biomarkers for mechanical asphyxia. OGG1 can maintain mtDNA integrity and maintain the stability of the mitochondrial membrane.

The down-regulation of STC2 mRNA may serve as a biomarker for death from mechanical asphyxia.

Death from mechanical asphyxia (DMA) is a common cause of death in forensic pathology. However, due to the lack of biomarkers, the authentication of DMA now relies on a series of non-specific signs, which may cause troubles in the judicial trials, especially when the criminal scene is not fully elucidated. To search for the potential biomarkers for DMA, brain samples of DMA and craniocerebral injury groups were screened by microarray. The obtained mRNAs were validated by animal and human samples. Primary cell culture was conducted to explore the biochemical changes under hypoxia. 415 differentially expressed mRNAs between two groups were discovered. Ten mRNAs were examined in both human and animal samples died of different causes of death. Stanniocalcin-2 (STC2) showed significant down-regulation in DMA samples compared to other groups, regardless of PMI, age, or temperature. Cellular experiments indicated that ROS level peaked after 15-min-hypoxic culture, when the expression level of STC2 was significant down-regulated simultaneously. The ER-stress-related proteins also showed potential connection with STC2. In general, it is indicated that the down-regulation of STC2 may serve as a biomarker for DMA.

The selection of endogenous genes in human postmortem tissues.

Precisely determining the postmortem interval (PMI), which is crucial to criminal and forensic cases, is a research in which quantitative RT-PCR (also known as qRT-PCR or real-time RT-PCR) has been used to analyse gene expression levels and data normalisation should be required to eliminate the differences among the samples. Therefore, it is quite necessary to find stable molecular biological markers in PMI determination research. In this study, we compared nine commonly used endogenous markers (containing ACTB, GAPDH, B2M, U6, 18S rRNA, hsa-mir-1, hsa-mir-9, hsa-mir-194-1 and hsa-mir-203) in the 109 human tissue samples obtained from autopsy at the aim of finding stable markers in human tissues with consideration of the impact of parameters (PMI and cause of death). After RNA was extracted from four tissues (heart, brain, kidney, skin), the Ct values of nine endogenous markers were obtained by qRT-PCR and assessed by geNorm software. The results showed that U6, GAPDH and 18S rRNA were the suitable markers in our set of samples in various corpse conditions, that B2M and ACTB were reliable internal controls in heart tissue only, and that microRNAs had such high M values that they should not be chosen for endogenous control genes.