Identification of Blood Biomarkers in Ischemic Stroke by Integrated Analysis of Metabolomics and Proteomics.

We aimed to uncover the pathological mechanism of ischemic stroke (IS) using a combined analysis of untargeted metabolomics and proteomics. The serum samples from a discovery set of 44 IS patients and 44 matched controls were analyzed using a specific detection method. The same method was then used to validate metabolites and proteins in the two validation sets: one with 30 IS patients and 30 matched controls, and the other with 50 IS patients and 50 matched controls. A total of 105 and 221 differentially expressed metabolites or proteins were identified, and the association between the two omics was determined in the discovery set. Enrichment analysis of the top 25 metabolites and 25 proteins in the two-way orthogonal partial least-squares with discriminant analysis, which was employed to identify highly correlated biomarkers, highlighted 15 pathways relevant to the pathological process. One metabolite and seven proteins exhibited differences between groups in the validation set. The binary logistic regression model, which included metabolite 2-hydroxyhippuric acid and proteins APOM_O95445, MASP2_O00187, and PRTN3_D6CHE9, achieved an area under the curve of 0.985 (95% CI: 0.966-1) in the discovery set. This study elucidated alterations and potential coregulatory influences of metabolites and proteins in the blood of IS patients.

Manipulation of topological antichiral edge states by inducing valley-chirality coupling.

Benefiting from the non-uniform assigning on the sublattices A and B in a modified Haldane model, the reductions of both spatial inversion and time-reversal symmetries can be induced to implement the competition of valley and chirality, which provide us a new, to the best of our knowledge, means to manipulate the topological antichiral edge states (ACEs). An implementation method for harnessing ACEs in a two-dimensional gyromagnetic photonic crystal (PC) has been proposed, which reveals that the opposite magnetization applied in the cylinders of sublattices A and B can generate the ACEs, and the valley Hall phase induced by dimerization of the structure further manipulates the edge states. Moreover, we found that the one-way dual transport channels of the ACEs can be transformed from both upper and lower zigzag edges into only one channel due to the propagating direction mismatched in the gyromagnetic PC heterojunction structure. Our research enriches the understanding of antichiral one-way transport states and offers useful insights and routines to design novel topological electromagnetic and optical functional devices.

Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway.

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

Short term efficacy of subtalar arthroscopy combined with medial calcaneal-talar joint distraction in minimally invasive treatment of diabetic patients with calcaneal fractures: a retrospective study.

BACKGROUND: The surgical treatment and management of postoperative soft tissue complications in diabetic patients with displaced calcaneal fractures are still controversial. We aimed to evaluate the short-term efficacy of percutaneous minimally invasive screw fixation in treatment of diabetic patients with Sanders II and III calcaneal fractures under subtalar arthroscopy assisted by preoperative musculoskeletal ultrasonic locating lateral calcaneal branch (LCB) of the sural nerve and calcaneal-talar joint distraction device. METHODS: The clinical data of 52 diabetic patients diagnosed with Sanders II or III calcaneal fractures from March 2016 to August 2020 were followed up and analyzed. There were 23 patients of type II and 29 patients of type III, 34 males and 18 females, with a mean age of 61.7 ± 14.5 years (range: 45-72 years). Preoperative musculoskeletal ultrasonography was routinely examined to locate LCB of the sural nerve. During surgery, we performed arthroscopic percutaneous prying reduction screw fixation assisted by medial calcaneal-talar joint distraction. Incision healing, local skin paraesthesia and other conditions were observed regularly at 3 days, 6, 12 months, and the last follow-up after surgery. Also, we measured the length, width, height, Böhler angle, and Gissane angle of the calcaneus on lateral and axial x-rays. Visual analogue pain scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) score and Maryland score were used to evaluate the efficacy. RESULTS: 52 patients were followed up for 23.7 ± 3.2 months (range: 20-28 months) without incision-related complications. Calcaneal radiographic parameters (length, width, height, Böhler/Gissane angle) were improved after surgery, and the differences were all statistically significant (P<0.05). There was no difference between calcaneal radiographic parameters at 6,12 months and the last follow-up compared with 3 days after surgery without significant loss in overall morphology (P>0.05). Postoperative VAS, AOFAS scores, and Maryland scores were significantly improved compared with those before surgery (P<0.05). CONCLUSIONS: Preoperative ultrasonic locating LCB of the sural nerve and arthroscopic percutaneous minimally invasive screw fixation of Sanders II and III calcaneal fractures with the assistance of calcaneal-talar joint distraction have good short-term efficacy and clinical feasibility in diabetic patients.

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis.

Osteoarthritis is a heterogeneous disease with a complex etiology. However, there is no effective treatment strategy at present. The purpose of this study was to explore the miRNA‒mRNA regulatory network and molecular mechanism that regulate the progression of osteoarthritis. In this article, we downloaded datasets (GSE55457, GSE82107, GSE143514 and GSE55235) from Gene Expression Omnibus (GEO) to screen differentially expressed mRNAs in osteoarthritis. Then, through weighted gene coexpression network (WGCNA), functional enrichment, protein‒protein interaction (PPI) network, miRNA‒mRNA coexpression network, ROC curve, and immune infiltration analyses and qPCR, the mRNA PLCD3, which was highly expressed in osteoarthritis and had clinical predictive value, was screened. We found that PLCD3 directly targets miR-34a-5p through DIANA and dual-luciferase experiments. The expression levels of PLCD3 and miR-34a-5p were negatively correlated. In addition, CCK-8 and wound healing assays showed that the miR-34a-5p mimic inhibited hFLS-OA cell proliferation and promoted hFLS-OA cell migration. PLCD3 overexpression showed the opposite trend. Western blotting further found that overexpression of miR-34a-5p reduced the protein expression levels of p-PI3K and p-AKT, while overexpression of PLCD3 showed the opposite trend. In addition, combined with the effect of the PI3K/AKT pathway inhibitor BIO (IC50 = 5.95 µM), the results showed that overexpression of miR-34a-5p increased the inhibitory effects of BIO on p-PI3K and p-AKT protein expression, while overexpression of PLCD3 significantly reversed these inhibitory effects. Overall, the miR-34a-5p/PLCD3 axis may mediate the PI3K/AKT pathway in regulating cartilage homeostasis in synovial osteoarthritis. These data indicate that miR-34a-5p/PLCD3 may be a new prognostic factor in the pathology of synovial osteoarthritis.

Spin-dependent and tunable perfect absorption in a Fabry-Perot cavity containing a multi-Weyl semimetal.

Spin-dependent absorption has been widely studied in metamaterials and metasurfaces with chirality since it develops significant applications in multiplexed holograms, photodection, and filtering. Here, the one-dimensional photonic crystal Fabry-Perot (FP) cavity containing a multi-Weyl semimetal (mWSM) defect is proposed to investigate the spin-dependent perfect absorption. Results denote that the distinct refractive indices of right hand circularly polarized (RCP) and left hand circularly polarized (LCP) waves are present due to the nonzero off-diagonal term of mWSM, thus supporting the perfect absorption of RCP and LCP waves at distinct resonant wavelengths. The different perfect absorption wavelengths of RCP and LCP waves reveal the spin-dependent perfect absorption. By altering the Fermi energy, tilt degree of Weyl cones, Weyl nodes separation, topological charge, and thickness of the mWSM layer, the perfect absorption wavelength of RCP and LCP waves can be regulated conveniently. Particularly, the linear tunable perfect absorption wavelength with thickness of the mWSM layer supports the accurate determination of perfect absorption wavelength at distinct mWSM thicknesses. Our studies develop simple and effective approaches to acquire the spin-dependent and adjustable perfect absorption without the external magnetic field, and can find practical applications in spin-dependent photonic devices.

Efficient second-harmonic generation based on off-Γ merging bound states in the continuum.

Ultracompact devices engineered for second-harmonic generation (SHG) hold a significant promise across a diverse spectrum of applications. Here, we propose a merging bound state in the continuum at an off-Γ point in a reciprocal space with the anisotropic materials lithium niobate. Such a merging BIC yields a profound reduction in radiative loss and scattering losses while concurrently exhibiting a substantial enhancement in the quality factor. As a result, we achieved a noteworthy SHG efficiency (η = 3.7%) at the incident angle θ = 10° when the pump intensity I0 = 2 kW/cm2, outperforming alternative nanostructures designed for SHG. This research contributes valuable insights into the feasibility of metadevices founded on the principles of nanoengineering applied to traditional nonlinear crystals. Such advancements hold a considerable promise for the development of compact, high-performance SHG devices across a range of applications.

Multi-topological state via the Brillouin zone overlap for nonlinear frequency conversion.

Multiband topological edge states (TESs) or topological corner states (TCSs) in photonic crystals provide effective ways to manipulate the nonlinear frequency conversions. However, the deliberate design and the limited number of multibands lead to the difficulty of experimental realization of the topological nonlinear frequency conversion or higher harmonic generation. Here, we propose an effective method to achieve multiple TESs and TCSs by combining the Brillouin zones of multiple different systems. It is shown that the spectra of the subsystems disperse into different energy levels due to the inter-system hopping. Based on this approach, we construct a topological photonic crystal based on the Brillouin zone overlapped SSH model, which enables the overlapped TCSs to participate in nonlinear frequency conversion. Our scheme can provide a significant way to realize the topological nonlinear frequency conversion with double resonances or multiple resonances.

Second harmonic generation by matching the phase distributions of topological corner and edge states.

Second harmonic generation (SHG) in topological photonic crystals is chiefly concerned with frequency conversion between the same topological states. However, little attention has been paid to the effect of coupling between different topological states on the SHG. In this study, we propose a method for achieving optimal SHG in a topological cavity by matching the phase distributions of the electric fields of the topological corner state (TCS) and topological edge state (TES). Our results show that the intrinsic efficiency can be improved when the phase distributions of the fundamental wave within the TCS and the second harmonic wave within the TES have the same symmetry. Otherwise, conversion efficiency will be greatly inhibited. With this method, we achieved an optimal intrinsic efficiency of 0.165%. Such a platform may enable the development of integrated nanoscale light sources and on-chip frequency converters.

Induction and metabolomic analysis of hairy roots of Atractylodes lancea.

Atractylodes lancea is an important source of traditional Chinese medicines. Sesquiterpenoids are the key active compounds in A. lancea, and their presence determines the quality of the material. Hairy hoot (HR) culture is a potential method to produce medicinally active compounds industrially; however, the induction and metabolic profiling of A. lancea HR have not been reported. We found that optimal induction of A. lancea HR was achieved by Agrobacterium rhizogenes strain C58C1 using the young leaves of tissue culture seedlings in the rooting stage as explants. Ultra-performance liquid chromatography-tandem mass spectrometric analyses of the chemical compositions of HR and normal root (NR) led to the annotation of 1046 metabolites. Over 200 differentially accumulated metabolites were identified, with 41 found to be up-regulated in HR relative to NR and 179 down-regulated in HR. Specifically, atractylodin levels were higher in HR, while the levels of ß-eudesmol and hinesol were higher in NR. Metabolic pathway analyses showed a significant difference in metabolites of the shikimate acid pathway between HR and NR. Five A. lancea compounds are potential biomarkers for evaluation of HR and NR quality. This study provides an important reference for the application of HR for the production of medicinally active compounds. KEY POINTS: • We established an efficient protocol for the induction of HR in A. lancea • HR was found to have a significantly higher amount of atractylodin than did NRs • Metabolic pathway analyses showed a significant difference in metabolites of the shikimate acid pathway between HR and NR.

Proteomic advance of ischemic stroke: preclinical, clinical, and intervention.

Ischemic stroke (IS) is the most common type of stroke and is characterized by high rates of mortality and long-term injury. The prediction and early diagnosis of IS are therefore crucial for optimal clinical intervention. Proteomics has provided important techniques for exploring protein markers associated with IS, but there has been no systematic evaluation and review of research that has used these techniques. Here, we review the differential proteins that have been found in cell- and animal- based studies and clinical trials of IS in the past 10 years; determine the key pathological proteins that have been identified in clinical trials; summarize the target proteins affected by interventions aimed at treating IS, with a focus on traditional Chinese medicine treatments. Overall, we clarify findings and problems that have been identified in recent proteomics research on IS and provide suggestions for improvements in this area. We also suggest areas that could be explored for determining the pathogenesis and developing interventions for IS.

Celastrol alleviates oxidative stress induced by multi-walled carbon nanotubes through the Keap1/Nrf2/HO-1 signaling pathway.

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Evaluation of subchronic toxicity of the compound of diphenhydramine hydrochloride and caffeine after 28 days of repeated oral administration in Sprague-Dawley rats and beagle dogs.

This study was designed to evaluate the subchronic toxicity of the compound of diphenhydramine hydrochloride (DH) and caffeine in Sprague-Dawley (SD) rats and beagle dogs. A total of 180 SD rats (15/sex/group) were randomly divided into the compound low-, medium- and high-dose groups (51, 102, 204 mg/kg), DH group (60 mg/kg), caffeine group (144 mg/kg) and the vehicle control group. Sixty beagle dogs (5/sex/group) were randomly divided into the compound low-, medium- and high-dose groups (male: 14.20, 28.30, 56.60 mg/kg, female: 5.66, 14.20, 28.30 mg/kg), DH group (male: 16.60 mg/kg, female: 8.30 mg/kg), caffeine group (male: 40.00 mg/kg, female: 20.00 mg/kg) and the vehicle control group. Rats and dogs were given continuous oral administration for 28 days following a 28-day recovery period. The adverse effects of the compound on rats and beagle dogs mainly included anorexia and liver function impairment. Most adverse effects induced by administration were reversible. Under the experimental conditions, the no-observed-adverse-effect level (NOAEL) of the compound of DH and caffeine was 51 mg/kg/day for SD rats and 28.30 mg/kg/day (male) and 5.66 mg/kg/day (female) for beagle dogs.

Sensitivity-Tunable Terahertz Liquid/Gas Biosensor Based on Surface Plasmon Resonance with Dirac Semimetal.

In this paper, we study the sensitivity-tunable terahertz (THz) liquid/gas biosensor in a coupling prism-three-dimensional Dirac semimetal (3D DSM) multilayer structure. The high sensitivity of the biosensor originates from the sharp reflected peak caused by surface plasmon resonance (SPR) mode. This structure achieves the tunability of sensitivity due to the fact that the reflectance could be modulated by the Fermi energy of 3D DSM. Besides, it is found that the sensitivity curve depends heavily on the structural parameters of 3D DSM. After parameter optimization, we obtained sensitivity over 100°/RIU for liquid biosensor. We believe this simple structure provides a reference idea for realizing high sensitivity and a tunable biosensor device.

[Application of tissue culture technology of medicinal plants in sustainable development of Chinese medicinal resources].

Chinese medicinal resources are the cornerstone of the sustainable development of traditional Chinese medicine industry. However, due to the fecundity of species, over-exploitation, and limitations of artificial cultivation, some medicinal plants are depleted and even endangered. Tissue culture, a breakthrough technology in the breeding of traditional Chinese medicinal materials, is not limited by time and space, and can allow the production on an annual basis, which plays an important role in the protection of Chinese medicinal resources. The present study reviewed the applications of tissue culture of medicinal plants in the field of Chinese medicinal resources, including rapid propagation of medicinal plant seedlings, breeding of novel high-yield and high-quality cultivars, construction of a genetic transformation system, and production of secondary metabolites. Meanwhile, the current challenges and suggestions for the future development of this field were also proposed.

Prognostic signatures and potential pathogenesis of eRNAs-related genes in colon adenocarcinoma.

Enhancer RNAs (eRNAs) are a subclass of long noncoding RNAs (lncRNAs) that have a wide effect in human tumors. However, the systematic analysis of potential functions of eRNAs-related genes (eRGs) in colon cancer (CC) remains unexplored. In this study, a total of 8231 eRGs including 6236 protein-coding genes and 1995 lncRNAs were identified in CC based on the multiple resources. These eRGs showed higher expression level and stability compared to other genes. What's more, the functions of these eRGs were closely related to cancer. Then a prognostic prediction model with 12 eRGs signatures were obtained for colon adenocarcinoma (COAD) patients. ROC curves showed the AUCs were 0.81, 0.77, and 0.78 for 1-, 3-, and 5-year survival prediction, respectively. And the prognostic model also manifested good performance in the validation datasets. Besides, the expression levels of two prognostic signatures, TMEM220 and LRRN2, were verified to be significantly lower in CC tissues than in adjacent noncancerous tissues (p < .05). Finally, the distinct molecular features were characterized between the high- and low-risk group through multiomics analysis including DNA mutation and methylation. Our results show eRGs signatures based prognostic model has high accuracy and may provide innovative biomarkers in COAD.

Low threshold optical bistability based on topological edge state in photonic crystal heterostructure with Dirac semimetal.

The special band structure of three-dimensional Dirac semimetal (3D DSM) makes it show strong nonlinear optical characteristics in the terahertz region, which provides a new way to develop terahertz nonlinear devices with low threshold. In this paper, we theoretically study the optical bistability (OB) of transmitted light in a multilayer structure with 3D DSM embedded in two one-dimensional photonic crystals (1D PhC). The topological edge state (TES) excited by the 1D PhC heterostructure significantly enhances the local electric field near the nonlinear 3D DSM, which provides a positive condition for the realization of low threshold OB. Through parameter optimization, we obtain a threshold electric field with an incident electric field of 106 V/m levels. Furthermore, the influences of the Fermi energy and thickness of 3D DSM and the angle of the incident light on the hysteretic behavior as well as the threshold of OB are clarified. 3D DSM-based optical devices with intrinsic OB provide a building block for future integrated optical and all-optical networks.

Higher-order nodal ring photonic semimetal.

The intriguing discovery of higher-order topology has tremendously promoted the development of topological physics. Three-dimensional topological semimetals have emerged as an ideal platform for investigating novel topological phases. Consequently, new proposals have been theoretically revealed and experimentally realized. However, most existing schemes are implemented on the acoustic system, while similar concepts are rarely launched in photonic crystals due to the complicated optical manipulation and geometrical design. In this Letter, we propose a higher-order nodal ring semimetal protected by C2 symmetry originating from C6 symmetry. The higher-order nodal ring is predicted in three-dimensional momentum space with desired hinge arcs connected by two nodal rings. Fermi arcs and topological hinge modes generate significant marks in higher-order topological semimetals. Our work successfully proves the presence of a novel higher-order topological phase in photonic systems that we will strive to apply practically in high-performance photonic devices.

Simultaneous slow light and sound rainbow trapping in phoxonic crystals.

In this paper, we use a phoxonic crystal (PxC) which can control the topological states of light and sound by breaking inversion symmetry and thus make it possible to achieve rainbow trapping of light and sound simultaneously. It is shown that topologically protected edge states can be obtained at the interfaces between PxCs with different topological phases. Thus, we designed a gradient structure to realize the topological rainbow trapping of light and sound by linearly modulating the structural parameter. In the proposed gradient structure, the edge states of light and sound modes with different frequencies are respectively trapped at different positions, owing to near zero group velocity. The topological rainbows of light and sound are simultaneously realized in one structure, which open a new, to the best of our knowledge, view and provide a feasible platform for the application of the topological optomechanical devices.

Retracted: Fangchinoline Promotes Autophagy and Inhibits Apoptosis in Osteoporotic Rats.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures.Reference:Wenjun Zhu, Wenge Ding, Xiaojun Shang, Ding Zhu, Xiaoyu Dai. Fangchinoline Promotes Autophagy and Inhibits Apoptosis in Osteoporotic Rats. Med Sci Monit, 2019; 25: 324-332. DOI: 10.12659/MSM.912624.