l-borneol promotes neurovascular unit protection in the subacute phase of transient middle cerebral artery occlusion rats: p38-MAPK pathway activation, anti-inflammatory, and anti-apoptotic effect.

Our previous study showed l-borneol reduced cerebral infarction in the acute stage after cerebral ischemia, but there is little about the study of subacute phase. We herein investigated the cerebral protective effects of l-borneol on neurovascular units (NVU) in the subacute phase after transient middle cerebral artery occlusion (t-MCAO). The t-MCAO model was prepared by the line embolus method. Zea Longa, mNss, HE, and TTC staining were used to evaluate the effect of l-borneol. We evaluated the mechanisms of l-borneol on inflammation, p38 MAPK pathway, and apoptosis, etc. through various technologies. l-borneol 0.2, 0.1, 0.05 g·kg-1 could significantly reduce cerebral infarction rate, alleviate the pathological injury, and inhibit inflammation reaction. l-borneol could also significantly increase brain blood supply, Nissl bodies, and the expression of GFAP. Additionally, l-borneol activated the p38 MAPK signaling pathway, inhibited cell apoptosis, and maintained BBB integrity. l-borneol had a neuroprotective effect, which was related to activating the p38 MAPK signaling pathway, inhibiting inflammatory response and apoptosis, and improving cerebral blood supply to protect BBB and stabilize and remodel NVU. The study will provide a reference for the use of l-borneol in the treatment of ischemic stroke in the subacute phase.

[Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats].

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-ß1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-ß1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

[Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway].

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1ß, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1ß, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1ß, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

A two-dimensional α-As/α-AsP van der Waals heterostructure for photovoltaic applications.

On the basis of first-principles calculations, we constructed a two-dimensional (2D) α-As/α-AsP van der Waals heterostructure (vdWH) to study the structural stability, and electronic and optical properties. Our results show that the 2D α-As/α-AsP vdWH displays indirect semiconductor characteristics with a band gap of 0.86 eV. Furthermore, it exhibits anisotropic properties and a high light absorption coefficient of up to 106 cm-1 in the ultraviolet region. Our predicted photoelectric conversion efficiency (PCE) of the 2D α-As/α-AsP vdWH reaches 21.30%, which is higher than those of blue-AsP/CdSe (13%), GeSe/AsP (16%), and As/tetracyanonaphtho-quinodimethane (TCNNQ) (20%). By applying an in-plane strain in the range from -6% to 6%, the band structure of the 2D α-As/α-AsP vdWH can be effectively tuned. In particular, under a uniaxial strain of -2% along the x-axis (2% along the y-axis), a transition from indirect to direct in the band structure occurs, while when applying a biaxial strain of -4% a transition from a semiconductor to a metal can be realized. These results indicate that the 2D α-As/α-AsP vdWH has potential applications in optoelectronic devices and solar cells.

d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model.

BACKGROUND: Cisplatin (CDDP) is commonly used to treat non-small cell lung cancer (NSCLC), but the appearance of drug resistance greatly hinders its efficacy. Borneol may promote drug absorption; however, synergism between borneol and CDDP in suppressing NSCLC is not clearly understood. Hence, we investigated borneol as a novel chemosensitizer to support chemotherapeutic efficacy and reduce side effects. METHODS: We compared viability after exposure to d-borneol, l-borneol, and synthetic borneol in two NSCLC cell lines, A549 and H460, and selected the most sensitive cells. We then assessed synergy between borneol forms and CDDP in cisplatin-resistant NSCLC cells, H460/CDDP. Next, we identified effective concentrations and exposure times. Subsequently, we evaluated cell migration via wound healing and cell proliferation via clone formation assay. Then, we focused on P-glycoprotein (P-gp) function, cell cycle, apoptosis, and RNA sequencing to elucidate underlying molecular mechanisms for synergy. Finally, we used an H460/CDDP xenograft tumor model to verify antitumor activity and safety in vivo. Data were examined using one-way analysis of variance (ANOVA) for multiple datasets or t-test for comparisons between two variables. RESULTS: d-Borneol was more effective in H460 than A549 cells. d-Borneol combined with CDDP showed greater inhibition of cell proliferation, migration, and clone formation in H460/CDDP cells than CDDP alone. RNA sequencing (RNA-seq) analysis identified differentially expressed genes enriched in cell cycle pathways. The impact of d-borneol on CDDP chemosensitivity involved arrest of the cell cycle at S phase via p27/p21-mediated cyclinA2/D3-CDK2/6 signaling and activation of intrinsic apoptosis via p21-mediated Bax/Bcl-2/caspase3 signaling. Further, d-borneol ameliorated drug resistance by suppressing levels and activity of P-gp. Cotreatment with d-borneol and CDDP inhibited tumor growth in vivo and reduced CDDP-caused liver and kidney toxicity. CONCLUSIONS: d-Borneol increased the efficacy of cisplatin and reduced its toxicity. This compound has the potential to become a useful chemosensitizer for drug-resistance NSCLC.

Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R-Ankrd1-P53 Signaling Pathway.

Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R-Ankrd1-P53 signaling pathway.

[Mechanism of Huanglian Houpo Decoction in treatment of ulcerative colitis in mice based on brain-gut axis].

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1ß, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.

Effect of stacking order and in-plane strain on the electronic properties of bilayer GeSe.

Germanium selenide as a new layered material is promising for nanoelectronic applications due to its unique optoelectronic properties and tunable band gap. In this study, based on density functional theory, we systematically investigated the structure, stability, and electronic properties of bilayer germanium selenide with four different stacking orders (namely AA-, AB-, AC- and AD-stacking). The obtained results indicated that the band gap is dependent on the stacking order with an indirect band gap for AA- and AC-stacking and direct band gap for AB- and AD-stacking. In addition, we also found that the band gap of the GeSe bilayer with different stacking orders can be tuned by in-plane strain. The transition between the direct to indirect band gap or semiconductor to metal is tunable. In particular, the direct band gap of the AB-stacking germanium selenide bilayer can be tuned in a wide energy range under applied strain along the armchair direction.

Oxidative treatment of diclofenac via ferrate(VI) in aqueous media: effect of surfactant additives.

The potential reaction of diclofenac (DCF) with ferrate(VI) and influences of coexisting surfactants have not been investigated in depth, and are the focus of this study. The results demonstrated that DCF reacted effectively and rapidly with Fe(VI) and approximately 75% of DCF (0.03 mM) was removed by excess Fe(VI) (0.45 mM) within 10 min. All of the reactions followed pseudo first-order kinetics with respect to DCF and Fe(VI), where the apparent second-order rate constant (kapp) was 5.07 M-1 s-1 at pH 9.0. Furthermore, the degradation efficiencies of DCF were clearly dependent on the concentrations of dissolved organic matter additives in the substrate solution. Primarily, inhibitory effects were observed with the samples that contained anionic (sodium dodecyl-benzene sulfonate, SDBS) or non-ionic (Tween-80) surfactants, which have been attributed to the side reactions between Fe(VI) and surfactants, which led to a reduction in the available oxidant for DCF destruction. Furthermore, the addition of a cationic surfactant (cetyltrimethyl ammonium bromide, CTAB) and humic acid (HA) conveyed significantly promotional effects on the DCF-Fe(VI) reaction. The rate enhancement effect for CTAB might be due to micellar surface catalysis, through the Coulomb attraction between the reactants and positively charged surfactants, while the catalytic action for HA resulted from the additional oxidation of Fe(V)/Fe(IV) in the presence of HA. The results provided the basic knowledge required to understand the environmental relevance of DCF oxidation via Fe(VI) in the presence of surfactant additives.

COD and Color Removal from Real Dyeing Wastewater by Ozonation.

Ozonation of real dye wastewater for removal of color and COD reduction covering a wide range in operating parameters forms the scope of the present work. The influence of parameters such as influent pH, ozone flow rate and initial effluent concentration on ozonation efficiency has been critically examined. It has been observed from the present investigation that a maximum of COD removal efficiency of 92.5% has been achieved under optimum operating conditions (pH=11; ozone flow rate: 6×10(-3) m(3)/minute). Further the biodegradability index of the dye effluent has increased from an initial value of 0.18 to 0.49 during ozonation indicating favorable adaptation of ozonation as a primer to the biochemical technique to enhance the efficiency of biochemical treatment.

Advanced treatment of sodium acetate in water by ozone oxidation.

Ozone oxidation is an advanced oxidation process for treatment of organic and inorganic wastewater. In this paper, sodium acetate (according to chemical oxygen demand [COD]) was selected as the model pollutant in water, and the degradation efficiencies and mechanism of sodium acetate in water by ozone oxidation were investigated. The results showed that the ozone oxidation was an effective treatment technology for advanced treatment of sodium acetate in water; the COD removal rate obtained the maximum value of 45.89% from sodium acetate solution when the pH value was 10.82, ozone concentration was 100 mg/L, reaction time was 30 minutes, and reaction temperature was 25 degrees C. The COD removal rate increased first and decreased subsequently with the bicarbonate (HCO3-) concentration from 0 to 200 mg/L, the largest decline being 20.35%. The COD removal rate declined by 25.38% with the carbonate (CO3(2-)) concentration from 0 to 200 mg/L; CO3(2-) has a more obvious scavenging effect to inhibit the formation of hydroxyl free radicals than HCO3-. Calcium chloride (CaCl2) and calcium hydroxide (Ca(OH)2) could enhance the COD removal rate greatly; they could reach 77.35 and 96.53%, respectively, after a reaction time of 30 minutes, which was increased by 31.46 and 50.64%, respectively, compared with only ozone oxidation. It was proved that the main ozone oxidation product of sodium acetate was carbon dioxide (CO2), and the degradation of sodium acetate in the ozone oxidation process followed the mechanism of hydroxyl free radicals.

l-Borneol and d-Borneol promote transdifferentiation of astrocytes into neurons in rats by regulating Wnt/Notch pathway to exert neuroprotective effect during recovery from cerebral ischaemia.

BACKGROUND: The Chinese medicines Borneolum and l-Borneolum have neuroprotective effects on acute cerebral ischaemia-reperfusion (IR) in rats. Research on their effects during recovery from cerebral IR is lacking. Cerebral ischaemia can activate astrocytes for conversion into neurons. Neurogenesis cannot be achieved without nutritional support from an improved brain microenvironment through the blood circulation. PURPOSE: The purpose of this study was to determine whether Borneolum and l-Borneolum can promote transdifferentiation of astrocytes into neurons by regulating the Wnt/Notch pathway to exert neuroprotective effects during recovery from cerebral ischaemia. STUDY DESIGN AND METHODS: A suture crossing the external carotid artery to occlude the middle cerebral artery was used to prepare a model of cerebral IR (Longa et al., 1989). The Longa neurological function score, modified neurological severity score, tape removal test and grid misstep experiment were used to evaluate motor nerve function. Triphenyltetrazolium chloride was used to determine the extent of cerebral infarction. Left/right hemisphere contrast was used to measure brain atrophy. Astrocytes labelled with adeno-associated virus were used to track their fate after transdifferentiation. Laser speckle contrast imaging was used to observe the effects of l-Borneolum and Borneolum on cerebral blood flow. Immunofluorescence and western blotting were used to investigate their mechanisms. RESULTS: l-Borneolum and Borneolum significantly improved neurological function and limb movement in rats with cerebral ischaemia during recovery and increased cerebral blood flow. l-Borneolum improved forelimb motor coordination more effectively than Borneolum and promoted transdifferentiation of astrocytes to GABAergic neurons in the striatal region. The expression of Wnt3a and Notch-1 was downregulated. The expression of vascular endothelial growth factor was not significantly changed. Borneolum improved forelimb sensitivity and alleviated cerebral infarction and brain atrophy more effectively than l-Borneolum, which promoted transdifferentiation of astrocytes into neurons and nestin expression and neurogenesis in the striatal zone. The expression of glycogen synthase kinase-3ß and ß-catenin was upregulated. l-Borneolum and Borneolum had no significant neuroprotective effect on the cortex and hippocampus. CONCLUSIONS: l-Borneolum and Borneolum exerted neuroprotective effects on cerebral ischaemia during recovery by promoting neurogenesis and blood circulation in the striatal and subventricular zones. Their mechanisms may be related to the Wnt3a and Notch-1 pathways.

Computational Design of α-AsP/γ-AsP Vertical Two-Dimensional Homojunction for Photovoltaic Applications.

Based on first-principles calculations, we design a α-AsP/γ-AsP homojunction with minimum lattice distortion. It is found that the α-AsP/γ-AsP homojunction has an indirect bandgap with an intrinsic type-II band alignment. The proposed α-AsP/γ-AsP homojunction exhibits high optical absorption of 1.6×106 cm-1 along the zigzag direction. A high power conversion efficiency (PCE) of 21.08% is achieved in the designed α-AsP/γ-AsP homojunction, which implies it has potential applications in solar cells. Under 4% in-plane axial strain along the zigzag direction, a transition from indirect band gap to direct band gap is found in the α-AsP/γ-AsP homojunction. Moreover, the intrinsic type-II band alignment can be tuned to type-I band alignment under in-plane strain, which is crucial for its potential application in optical devices.

Neuroprotective effects of synthetic borneol and natural borneol based on the neurovascular unit against cerebral ischaemic injury.

OBJECTIVES: Natural borneol and synthetic borneol were commonly used to treat ischaemic stroke in clinical practice. This study evaluated their different neuroprotective effects on the remodelling and repair of the neurovascular unit (NVU) after cerebral ischaemia. METHODS: We evaluated the different effects of borneol through neurological test and staining methods in cerebral ischaemia injury. Western blot, immunohistochemistry and transmission electron microscopy were used to evaluate the reparative effects of borneol on NVU. KEY FINDINGS: The prevention and treatment of borneol could prolong recovery time, reduce body temperature and cerebral infarction rate and improve pathological conditions. Further investigations revealed that borneol could inhibit the expression of DII4, Hes1, Hes5 and p65 and increase the Nissl body number and microvessel density. They also inhibited the activation of the microglia. It was also observed through an ultramicroelectron microscope that the structural stability of the NVU has also been repaired. Moreover, natural borneol shows better results in most indicators when compared with synthetic borneol. CONCLUSIONS: Natural borneol showed a stronger effectiveness and had better regulation and neuroprotection on the NVU when compared with synthetic borneol, indicating that it may be better to use natural borneol in the prescription of Chinese patent medicine in clinical practice.

d-Borneol enhances cisplatin sensitivity via autophagy dependent EMT signaling and NCOA4-mediated ferritinophagy.

BACKGROUND: d-Borneol has been widely used as a drug absorption enhancer, but there are few studies on the anti-resistance ability of d-borneol combined with cisplatin in cisplatin-resistant non-small cell lung cancer cells. Ferroptosis, autophagy and epithelial-mesenchymal transition (EMT) have been reported to be associated with drug resistance. PURPOSE: To investigate the molecular mechanisms and sensitizing effects of d-borneol combined with cisplatin to against drug cisplatin resistance from the perspective of ferroptosis, autophagy and EMT resistance. METHODS: H460/CDDP xenograft tumor model was established to verify the antitumor activity and safety in vivo. RNA sequencing was used to predict target molecules and signaling pathways. Reactive oxygen species (ROS) were used as marker of ferroptosis, and its level was determined by a dichlorodihydrofluorescein diacetate fluorescent probe and flow cytometry. Levels of glutathione (GSH), malondialdehyde (MDA), and antioxidants such as superoxide dismutase (SOD) and thioredoxin (Trx) involved in the balance of oxidative stress were measured by an assay kit or enzyme-linked immunosorbent assay. Western blotting and real-time polymerase chain reaction were used to assess the regulatory mechanism of EMT markers, autophagy, and ferroptosis signaling pathways. RESULTS: d-Borneol in combination with cisplatin reduced tumor volume and weight, enhanced tumor-inhibiting effects, and alleviated cisplatin-induced damage to the liver and kidney in vivo. RNA-sequencing showed that differentially expressed genes were enriched in ferroptosis. d-Borneol in combination with cisplatin promoted ROS accumulation, increased the content of MDA levels, and decreased GSH, SOD, Trx, and heme oxygenase-1 expression to induce oxidative damage. d-Borneol combination with cisplatin induced ferroptosis by promoting nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and regulating intracellular iron ion transport via upregulating PRNP and downregulating PCBP2. In addition, d-borneol combined with cisplatin promoted autophagy by upregulating expression of LC3II/ATG5/Beclin-1 and inhibited the EMT by increasing the expression of epithelial marker E-cadherin and decreasing mesenchymal markers (N-cadherin and vimentin) and transcription factors (Snail and ZEB1). CONCLUSION: For the first time, our study implies that d-borneol enhanced cisplatin sensitivity by inducing ferroptosis, promoting autophagy and inhibiting EMT progression, thereby enhancing antitumor activity. It suggests that d-borneol could be developed as a novel chemosensitizers.

1D/2D van der Waals Heterojunctions Composed of Carbon Nanotubes and a GeSe Monolayer.

Based on first-principles calculations, we propose van der Waals (vdW) heterojunctions composed of one-dimensional carbon nanotubes (CNTs) and two-dimensional GeSe. Our calculations show that (n,0)CNT/GeSe (n = 5-11) heterojunctions are stable through weak vdW interactions. Among these heterojunctions, (n,0)CNT/GeSe (n = 5-7) exhibit metallic properties, while (n,0)CNT/GeSe (n = 8-11) have a small bandgap, lower than 0.8 eV. The absorption coefficient of (n,0)CNT/GeSe (n = 8-11) in the ultraviolet and infrared regions is around 105 cm-1. Specifically, we found that (11,0)CNT/GeSe exhibits type-II band alignment and has a high photoelectric conversion efficiency of 17.29%, which suggests prospective applications in photoelectronics.

Storax, A Promising Botanical Medicine for Treating Cardio-Cerebrovascular Diseases: A Review.

In recent years, the incidence and mortality of cardio-cerebrovascular diseases have been increasing year by year, which has become global burden and challenge. Based on the holistic thinking of "brain disease affects the heart" and "heart disease affects the brain," as well as the characteristics of multi-target and multi-path effects of Chinese medicine, Chinese medicine is more advantageous in the treatment of cardio-cerebrovascular diseases. As a botanical medicine, storax is known for its resuscitation, filth avoidance and pain-relieving effects in the treatment of cardio-cerebrovascular diseases. By reviewing and collating the relevant domestic and international literature in the past 10 years, we have sorted out an overview of the medicinal parts, traditional uses and chemical composition of storax. For the first time, based on the idea of "cerebral and cardiac simultaneous treatment," the pharmacological activities and mechanisms of heart and brain protection of storax for treating cardio-cerebrovascular diseases were summarized and analyzed, showing that storax has the pharmacological effects of anti-cerebral ischemia, regulation of blood-brain barrier, bidirectional regulation of the central nervous system, anti-myocardial ischemia, anti-arrhythmia, anti-thrombosis and anti-platelet aggregation. It mainly exerts its protective effects on the brain and heart through mechanisms such as inhibition of inflammatory immune factors, anti-oxidative stress, anti-apoptosis, pro-neovascularization and regulation of NO release. On the basis of the current findings and limitations, the future research strategies and perspectives of storax are proposed, with a view to providing a reference for further application and development of this medicine, as well as contributing new thoughts and visions for the clinical application of "treating brain-heart synchronously".

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review.

Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it's reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.

Application and advantages of zebrafish model in the study of neurovascular unit.

The concept of "Neurovascular Unit" (NVU) was put forward, so that the research goal of Central Nervous System (CNS) diseases gradually transitioned from a single neuron to the structural and functional integrity of the NVU. Zebrafish has the advantages of high homology with human genes, strong reproductive capacity and visualization of neural circuits, so it has become an emerging model organism for NVU research and has been applied to a variety of CNS diseases. Based on CNKI (https://www.cnki.net/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/about/) databases, the author of this article sorted out the relevant literature, analyzed the construction of a zebrafish model of various CNS diseases，and the use of diagrams showed the application of zebrafish in the NVU, revealed its relationship, which would provide new methods and references for the treatment and research of CNS diseases.