Monolayer Borophene Formation on Cu(111) Surface Triggered by ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ Step Edge.

Borophene, a promising material with potential applications in electronics, energy storage, and sensors, is successfully grown as a monolayer on Ag(111), Cu(111), and Au(111) surfaces using molecular beam epitaxy. The growth of two-dimensional borophene on Ag(111) and Au(111) is proposed to occur via surface adsorption and boron segregation, respectively. However, the growth mode of borophene on Cu(111) remains unclear. To elucidate this, scanning tunneling microscopy in conjunction with theoretical calculations is used to study the phase transformation of boron nanostructures under post-annealing treatments. Results show that by elevating the substrate temperature, boron nanostructures undergo an evolution from amorphous boron to striped-phase borophene (η = 1/6) adhering to the Cu ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ step edge, and finally to irregularly shaped ß-type borophene (η = 5/36) either on the substrate surface or embedded in the topmost Cu layer. dI/dV spectra recorded near the borophene/Cu lateral interfaces indicate that the striped-phase borophene is a metastable phase, requiring more buckling and electron transfer to stabilize the crystal structure. These findings offer not only an in-depth comprehension of the ß-type borophene formation on Cu(111), but also hold potential for enabling borophene synthesis on weakly-binding semiconducting or insulating substrates with 1D active defects.

Creation of Interfacial S4 -Sn-N2 Electron Pathways for Efficient Light-Driven Hydrogen Evolution.

Establishing effective charge transfer channels between two semiconductors is key to improving photocatalytic activity. However, controlling hetero-structures in situ and designing binding modes pose significant challenges. Herein, hydrolytic SnCl2 ·2H2 O is selected as the metal source and loaded in situ onto a layered carbon nitriden supramolecular precursor. A composite photocatalyst, S4 -Sn-N2 , with electron pathways of SnS2 and tubular carbon nitriden (TCN) is prepared through pyrolysis and vulcanization processes. The contact interface of SnS2 -TCN is increased significantly, promoting the formation of S4 -Sn-N2 micro-structure in a Z-scheme charge transfer channel. This structure accelerates the separation and transport of photogenerated carriers, maintains the stronger redox ability, and improves the stability of SnS2 in this series of heterojunctions. Therefore, the catalyst demonstrated exceptional photocatalytic hydrogen production efficiency, achieving a reaction rate of 86.4 µmol h-1 , which is 3.15 times greater than that of bare TCN.

FragGrow: A Web Server for Structure-Based Drug Design by Fragment Growing within Constraints.

Fragment growing is an important ligand design strategy in drug discovery. In this study, we present FragGrow, a web server that facilitates structure-based drug design by fragment growing. FragGrow offers two working modes: one for growing molecules through the direct replacement of hydrogen atoms or substructures and the other for growing via virtual synthesis. FragGrow works by searching for suitable fragments that meet a set of constraints from an indexed 3D fragment database and using them to create new compounds in 3D space. The users can set a range of constraints when searching for their desired fragment, including the fragment's ability to interact with specific protein sites; its size, topology, and physicochemical properties; and the presence of particular heteroatoms and functional groups within the fragment. We hope that FragGrow will serve as a useful tool for medicinal chemists in ligand design. The FragGrow server is freely available to researchers and can be accessed at https://fraggrow.xundrug.cn.

MolTaut: A Tool for the Rapid Generation of Favorable Tautomer in Aqueous Solution.

Fast and proper treatment of the tautomeric states for drug-like molecules is critical in computer-aided drug discovery since the major tautomer of a molecule determines its pharmacophore features and physical properties. We present MolTaut, a tool for the rapid generation of favorable states of drug-like molecules in water. MolTaut works by enumerating possible tautomeric states with tautomeric transformation rules, ranking tautomers with their relative internal energies and solvation energies calculated by AI-based models, and generating preferred ionization states according to predicted microscopic pKa. Our test shows that the ranking ability of the AI-based tautomer scoring approach is comparable to the DFT method (wB97X/6-31G*//M062X/6-31G*/SMD) from which the AI models try to learn. We find that the substitution effect on tautomeric equilibrium is well predicted by MolTaut, which is helpful in computer-aided ligand design. The source code of MolTaut is freely available to researchers and can be accessed at https://github.com/xundrug/moltaut. To facilitate the usage of MolTaut by medicinal chemists, we made a free web server, which is available at http://moltaut.xundrug.cn. MolTaut is a handy tool for investigating the tautomerization issue in drug discovery.

Hepatic venous gas secondary to pulmonary barotrauma: rat model study.

Intrahepatic gas (IHG) is commonly observed during early postmortem examinations of humans with upper or lower airway obstructions. We conducted a study to test the hypothesis that intrapulmonary gas could retrogradely spread to the hepatic vein following pulmonary barotrauma (PB). To establish a rat model of pulmonary barotrauma, we utilized a controllable pressure-vacuum pump to apply airway pressure (40, 60, or 80 mmHg). The rats were dissected directly at the end of the experiment, and histological analysis was performed through microscopic examination of the rats. Additionally, the rats were ventilated with meglumine diatrizoate under pressures of 160 and 250 mmHg to observe the signal dynamic diffusion using X-ray fluoroscopy examination. Rats exhibited classical changes associated with PB, such as alveolar rupture, pulmonary interstitial emphysema, and hemorrhage, as well as IHG characterized by the presence of gas in the hepatic vein and hepatic sinusoids. Air emboli were not observed in the liver in any of the 40 mmHg groups. However, they were observed in the liver in the 60 and 80 mmHg groups, the amount and size of air emboli in the 80 mmHg group were greater than those in the 60 mmHg group (p < 0.05). The 80 mmHg group presented radial grape-like bubbles in the centrilobular portion of the liver accompanied by congestion in the peripheral region of the hepatic lobule. X-ray fluoroscopy examination revealed a gradual enhancement of dynamic contrast medium signals from the lung to the inferior vena cava and then to the liver. Our findings indicate that pulmonary barotrauma can lead to the retrograde spread of intrapulmonary gas to the hepatic vein. When it is clear that no decomposition of the body has occurred, the presence of IHG serves as a novel indicator for the diagnosis of obstructive pulmonary disease or obstruction in the upper or lower airway.

MolHyb: A Web Server for Structure-Based Drug Design by Molecular Hybridization.

Molecular hybridization is a widely used ligand design method in drug discovery. In this study, we present MolHyb, a web server for structure-based ligand design by molecular hybridization. The input of MolHyb is a protein file and a seed compound file. MolHyb tries to generate novel ligands through hybridizing the seed compound with helper compounds that bind to the same protein target or similar proteins. To facilitate the job of getting helper compounds, we compiled a modeled protein-ligand structure database as an extension to crystal structures in the PDB database by placing the bioactive compounds in ChEMBL into their corresponding 3D protein binding pocket properly. MolHyb works by searching for helper compounds from the protein-ligand structure database and migrating chemical moieties from helper compounds to the seed compound efficiently. Hybridization is performed at both cyclic and acyclic bonds. The users can also input their own helper compounds to MolHyb. We hope that MolHyb will be a useful tool for rational drug design. MolHyb is freely available at http://molhyb.xundrug.cn/.

Recent Advances in Surface Modifications of Elemental Two-Dimensional Materials: Structures, Properties, and Applications.

The advent of graphene opens up the research into two-dimensional (2D) materials, which are considered revolutionary materials. Due to its unique geometric structure, graphene exhibits a series of exotic physical and chemical properties. In addition, single-element-based 2D materials (Xenes) have garnered tremendous interest. At present, 16 kinds of Xenes (silicene, borophene, germanene, phosphorene, tellurene, etc.) have been explored, mainly distributed in the third, fourth, fifth, and sixth main groups. The current methods to prepare monolayers or few-layer 2D materials include epitaxy growth, mechanical exfoliation, and liquid phase exfoliation. Although two Xenes (aluminene and indiene) have not been synthesized due to the limitations of synthetic methods and the stability of Xenes, other Xenes have been successfully created via elaborate artificial design and synthesis. Focusing on elemental 2D materials, this review mainly summarizes the recently reported work about tuning the electronic, optical, mechanical, and chemical properties of Xenes via surface modifications, achieved using controllable approaches (doping, adsorption, strain, intercalation, phase transition, etc.) to broaden their applications in various fields, including spintronics, electronics, optoelectronics, superconducting, photovoltaics, sensors, catalysis, and biomedicines. These advances in the surface modification of Xenes have laid a theoretical and experimental foundation for the development of 2D materials and their practical applications in diverse fields.

Porous Carbon Nitride Thin Strip: Precise Carbon Doping Regulating Delocalized π-Electron Induces Elevated Photocatalytic Hydrogen Evolution.

The photocatalytic efficiency of polymeric carbon nitride is hampered by high carrier recombination rate and low charge transfer. Herein, these issues are addressed by constructing 1D strip-like carbon nitride with a large π-electron conjugated system from carbon-doping, realizing the synchronization control of its electronic structure and morphology. Nicotinic acid, a monomer with the carboxyl group and pyridine ring, and melamine are selected for assembling the strip-like supramolecular via hydrogen bond under hydrothermal process. Both peripheral pyridine unit and hydrogen bond have significant effect on self-assembly process of nicotinic acid and melamine along one dimension to form a strip-like precursor. Subsequently, 1D thin porous strip-like carbon nitride is obtained by calcination treatment of precursor. The as-prepared 1D strip-like carbon nitride with effective π delocalization from carbon-doping and porous structure can accelerate charges and mass transfer and provide extra active sites. Both theoretical and experimental results demonstrate that carbon doping (pyridine heterocycle) narrows the bandgap via manipulating the band position and increases the π electron density. Thus, the 1D porous thin strip-like carbon nitride realizes compelling hydrogen evolution rate (126.2 µmol h-1 ), far beyond (≈18 fold) the value of polymeric carbon nitride (PCN) (7.2 µmol h-1 ) under visible light irradiation.

Reversible structural transition of two-dimensional copper selenide on Cu(111).

Structural engineering opens a door to manipulating the structures and thus tuning the properties of two-dimensional materials. Here, we report a reversible structural transition in honeycomb CuSe monolayer on Cu(111) through scanning tunneling microscopy and Auger electron spectroscopy (AES). Direct selenization of Cu(111) gives rise to the formation of honeycomb CuSe monolayers with one-dimensional moiré structures (stripe-CuSe), due to the asymmetric lattice distortions in CuSe induced by the lattice mismatch. Additional deposition of Se combined with post annealing results in the formation of honeycomb CuSe with quasi-ordered arrays of triangular holes (hole-CuSe), namely, the structural transition from stripe-CuSe to hole-CuSe. Further, annealing the hole-CuSe at higher temperature leads to the reverse structural transition, namely from hole-CuSe to stripe-CuSe. AES measurement unravels the Se content change in the reversible structural transition. Therefore, both the Se coverage and annealing temperature play significant roles in the reversible structural transition in CuSe on Cu(111). Our work provides insights in understanding of the structural transitions in two-dimensional materials.

A survey of current practices, attitudes and demands of anaesthesiologists regarding the depth of anaesthesia monitoring in China.

BACKGROUND: In this study, we aimed to analyse survey data to explore two different hypotheses; and for this purpose, we distributed an online survey to Chinese anaesthesiologists. The hypothetical questions in this survey include: (1) Chinese anaesthesiologists mainly use the depth of anaesthesia (DoA) monitors to prevent intraoperative awareness and (2) the accuracy of these monitors is the most crucial performance factor during the clinical daily practice of Chinese anaesthesiologists. METHODS: We collected and statistically analysed the response of a total of 12,750 anesthesiologists who were invited to participate in an anonymous online survey. The Chinese Society of Anaesthesiologists (CSA) trial group provided the email address of each anaesthesiologist, and the selection of respondents was random from the computerized system. RESULTS: The overall response rate was 32.0% (4037 respondents). Only 9.1% (95% confidence interval, 8.2-10.0%) of the respondents routinely used DoA monitors. Academic respondents (91.5, 90.3-92.7%) most frequently used DoA monitoring to prevent awareness, whereas nonacademic respondents (88.8, 87.4-90.2%) most frequently used DoA monitoring to guide the delivery of anaesthetic agents. In total, the number of respondents who did not use a DoA monitor and whose patients experienced awareness (61.7, 57.8-65.6%) was significantly greater than those who used one or several DoA monitors (51.5, 49.8-53.2%). Overall, the crucial performance factor during DoA monitoring was considered by 61.9% (60.4-63.4%) of the respondents to be accuracy. However, most respondents (95.7, 95.1-96.3%) demanded improvements in the accuracy of the monitors for DoA monitoring. In addition, broad application in patients of all ages (86.3, 85.2-87.4%), analgesia monitoring (80.4, 79.2-81.6%), and all types of anaesthetic agents (75.6, 74.3-76.9%) was reported. In total, 65.0% (63.6-66.5%) of the respondents believed that DoA monitors should be combined with EEG and vital sign monitoring, and 53.7% (52.1-55.2%) believed that advanced DoA monitors should include artificial intelligence. CONCLUSIONS: Academic anaesthesiologists primarily use DoA monitoring to prevent awareness, whereas nonacademic anaesthesiologists use DoA monitoring to guide the delivery of anaesthetics. Anaesthesiologists demand high-accuracy DoA monitors incorporating EEG signals, multiple vital signs, and antinociceptive indicators. DoA monitors with artificial intelligence may represent a new direction for future research on DoA monitoring.

FragRep: A Web Server for Structure-Based Drug Design by Fragment Replacement.

The design of efficient computational tools for structure-guided ligand design is essential for the drug discovery process. We hereby present FragRep, a new web server for structure-based ligand design by fragment replacement. The input is a protein and a ligand structure, either from protein data bank or from molecular docking. Users can choose specific substructures they want to modify. The server tries to find suitable fragments that not only meet the geometric requirements of the remaining part of the ligand but also fit well with local protein environments. FragRep is a powerful computational tool for the rapid generation of ligand design ideas; either in scaffold hopping or bioisosteric replacing. The FragRep Server is freely available to researchers and can be accessed at http://xundrug.cn/fragrep.

A two-dimensional ErCu2 intermetallic compound on Cu(111) with moiré-pattern-modulated electronic structures.

A rare-earth compound on a metal may form a two-dimensional (2D) intermetallic compound whose properties can be further modulated by the underlying substrate periodicity and coupling. Here, we present a combinational and systematic investigation using scanning tunneling microscopy/spectroscopy (STM/STS) and density functional theory (DFT) calculations on erbium (Er) on Cu(111). Experimentally, an intriguing growth mode transition from a branched island to a fractal-like island has been observed depending on whether the deposition process of Er is interrupted for a certain duration: post-deposition effects, such as nucleation and island growth controlled by diffusion, play an essential role in altering the Er island edge and its activity. Upon annealing, the branched Er islands become strands of amorphous surface alloy; in contrast, the fractal-like islands (with additional Er atoms on top) give rise to a monolayer thick 2D ErCu2 intermetallic compound and display a moiré pattern. Theoretically, using DFT calculations, we found that the characteristic energy states, particularly the state in the unoccupied region around 582-663 meV, of the 2D ErCu2 intermetallic compound are position-dependent, consistent with STS measurements. The moiré pattern originating from the mismatch of the periodicities of the ErCu2 layer and the Cu(111) surface was identified to be responsible for the observed periodic modulation on the coupling interaction that affects the electronic structures. Our further DFT calculations on a free-standing ErCu2 monolayer found it to be a 2D ferromagnet with topological band structures. Our work should stimulate further studies on such 2D rare-earth-based nanostructures and exploration of the use of the tunable electronic structures in such atomically-thin layers.

Preparation of chitosan-based molecularly imprinted material for enantioseparation of racemic mandelic acid in aqueous medium by solid phase extraction.

An S-mandelic acid imprinted chitosan resin was synthesized by cross-linking chitosan with glutaraldehyde in 2% acetic acid solution. S-Mandelic acid imprinted chitosan resin was used to enantioselectively separate racemic mandelic acid in aqueous medium. When keeping the pH of sample solution (100 mM Tris-H3 PO4 ) at 3.5 and adsorption time at 40 min, the enantiomer excess of mandelic acid in supernatant was 78.8%. The adsorption capacities of S-mandelic acid imprinted chitosan resin for S- and R-mandelic acid were determined to be 29.5 and 2.03 mg/g, respectively. While the adsorption capacities of non-imprinted cross-linked chitosan for S- and R-mandelic acid were 2.10 and 2.08 mg/g, respectively. The result suggests that the imprinted caves in S-mandelic acid imprinted chitosan resin are highly matched with S-mandelic acid molecule in space structure and spatial arrangement of action sites. Interestingly, the enantiomer excess value of mandelic acid in supernatant after adsorption of racemic mandelic acid by R-mandelic acid imprinted cross-linked chitosan was 25.4%. The higher enantiomer excess value by S-mandelic acid imprinted chitosan resin suggests that the chiral carbons in chitosan and the imprinted caves in S-mandelic acid imprinted chitosan resin combine to play roles for the enantioselectivity of S-mandelic acid imprinted chitosan resin toward S-mandelic acid. Furthermore, the excellent enantioselectivity of S-mandelic acid imprinted chitosan resin toward S-mandelic acid demonstrates that using chiral chitosan as functional monomer to prepare molecularly imprinted polymers has great potential in enantioseparation of chiral pharmaceuticals.

Strongly Asymmetric Spectroscopy in Plasmon-Exciton Hybrid Systems due to Interference-Induced Energy Repartitioning.

Recent intense effort has been devoted to exploring different manifestations of resonant excitations of strongly coupled plasmons and excitons, but so far such studies have been limited to situations where the Fano- or Rabi-type spectra are largely symmetric at zero detuning. Using a newly developed full quantum mechanical model, here we reveal the existence of a highly asymmetric spectroscopic regime for both the Rabi splitting and transparency dip. The asymmetric nature is inherently tied to the non-negligible exciton absorbance and is caused by substantial interference-induced energy repartitioning of the resonance peaks. This theoretical framework can be exploited to reveal the quantum behaviors of the two excitation entities with varying mutual coupling strengths in both linear and nonlinear regimes. We also use prototypical systems of rhodamine molecules strongly coupled with AuAg alloyed nanoparticles and well-devised control experiments to demonstrate the validity and tunability of the energy repartitioning and correlated electronic state occupations, as captured by the variations in the asymmetric spectroscopy and corresponding nonlinear absorption coefficient as a function of the Au:Ag ratio. The present study helps to substantially enrich our microscopic understanding of strongly coupled plasmon-exciton systems.

Effects of terlipressin on patients with sepsis via improving tissue blood flow.

Terlipressin (TP), an analog of arginine vasopressin, was reported beneficial in sepsis patients when combined use with norepinephrine (NE), but the undetermined action, mechanism, and safety limited it to become the first-line vasopressor for sepsis patients. With 32 septic shock patients, we investigated the effects of a small dose of TP (1.3 µg/kg/h) on hemodynamic, tissue blood flow, vital organ function, acid-base balance, and coagulation function to systemically know the beneficial effect and side effects of TP on septic shock. The results showed that as compared with the single use of NE group (17 patients), a small dose of TP (1.3 µg/kg/h) in combination with NE continuous infusion, except for decreasing the mortality and NE requirement, could better improve and stabilize the hemodynamics, improve the tissue blood flow, increase the blood oxygen saturation and urine volume, and decrease the lactate level and complication rate (47% versus 82.3% in NE group). Meanwhile, TP + NE did not induce blood bilirubin increase and platelet count decrease and hyponatremia that vasopressin has. The results show that low dose of TP continuous infusion can help NE achieve the good resuscitation effect by improving tissue blood flow, stabilizing hemodynamics, and protecting organ function in septic shock patients while did not induce the side effects that high dose or bonus of TP or vasopressin induced. Low dose of TP may be recommended as the first-line vasopressor for refractory hypotension after severe sepsis or septic shock.

Controllable dissociations of PH3 molecules on Si(001).

We demonstrate for the first time to our knowledge that controllable dissociation of PH3 adsorption products PHx (x = 2, 1) can be realized by STM (scanning tunneling microscope) manipulation techniques at room temperature. Five dissociative products and their geometric structures are identified via combining STM experiments and first-principle calculations and simulations. In total we realize nine kinds of controllable dissociations by applying a voltage pulse among the PH3-related structures on Si(001). The dissociation rates of the five most common reactions are measured by the I-t spectrum method as a function of voltage. The suddenly increased dissociation rate at 3.3 V indicates a transition from multivibrational excitation to single-step excitation induced by inelastic tunneling electrons. Our studies prove that selectively breaking the chemical bonds of a single molecule on semiconductor surface by STM manipulation technique is feasible.

Protein markers related to vascular responsiveness after hemorrhagic shock in rats.

BACKGROUND: Vascular hyporesponsiveness is an important pathophysiological feature of some critical conditions such as hemorrhagic shock. Many proteins and molecules are involved in the regulation of the pathologic process, however the mechanism has still remained unclear. Our study was intended to look for the related protein markers involved in the regulation of vascular reactivity after hemorrhagic shock. METHODS: Differential in-gel electrophoresis and tandem mass spectrometry were applied to quantify the differences of protein expression in the superior mesenteric arteries from hemorrhagic shock and normal rats. RESULTS: A total of 2317 differentially expressed protein spots in the superior mesenteric arteries of rats before and after hemorrhagic shock were found, and 146 protein spots were selected for tandem mass spectrometry identification. Thirty-seven differentially expressed proteins were obtained, including 3 uncharacterized proteins and 34 known proteins. Among them, heat shock protein beta-1 and calmodulin were the known proteins involved in the occurrence of vascular hyporesponsiveness. Bioinformatics analysis results showed that 18 proteins were related to vasoconstriction, 11 proteins may be involved in other vascular functions such as regulation of angiogenesis and endothelial cell proliferation. CONCLUSIONS: The changes of vascular responsiveness after hemorrhagic shock in rats may be associated with the upregulation or downregulation of previously mentioned protein expressions. These findings may provide the basis for understanding and further study of the mechanism and treatment targets of vascular hyporeactivity after shock.

Beneficial and side effects of arginine vasopressin and terlipressin for septic shock.

Arginine vasopressin (AVP) and its analog, terlipressin (TP), were all demonstrated beneficial for septic shock. What advantages and disadvantages that AVP and TP have for septic shock as well as the mechanism, however, are not completely known. With cecal ligation and puncture-induced septic shock rats and lipopolysaccharide-induced septic shock rabbits, we systematically compared the beneficial and side effects of AVP and TP, in septic shock and the sex difference, and investigated their relationship to Rho kinase and calcium sensitivity. The results indicated that low dose of TP (2.6 µg/kg/h) in combination with norepinephrine (NE) improving vascular reactivity and animal survival were superior to a small dose of AVP (0.03 U/kg/h) in septic shock rats and rabbits. This improving effect of AVP and TP on vascular reactivity was closely related to the activation of Rho-kinase and Rho-kinase-mediating vascular calcium sensitization. A small dose of TP did not result in hyponatremia, did not increase blood bilirubin and decrease platelet count, whereas AVP did. Animal survival and vascular reactivity in female rats after TP or AVP administration were slightly better than male rats, while there were no significant differences. It was suggested that a small dose of TP has better beneficial effect and less side effects on septic shock than AVP. AVP and TP improving vascular reactivity is closely related to Rho-kinase activation and calcium sensitivity improvement. TP or plus NE may be more appropriate for early emergency care for severe septic shock than AVP.

Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways.

Several medical conditions exhibit age- and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4, 8, 10, 14, 18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age- and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17ß-estrdiol increased vascular reactivity in both male and femal rats of 8-24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR)30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age- and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age- and sex-related diseases involving estrogen.

Beneficial effects of platelet-derived growth factor on hemorrhagic shock in rats and the underlying mechanisms.

Studies have shown that local application of platelet-derived growth factor (PDGF) can be used for the treatment of acute and chronic wounds. We investigated if systemic application of PDGF has a protective effect on acute hemorrhagic shock in rats in the present study. Using hemorrhagic shock rats and isolated superior mesenteric arteries, the effects of PDGF-BB on hemodynamics, animal survival, and vascular reactivity as well as the roles of the gap junction proteins connexin (Cx)40 and Cx43, PKC, and Rho kinase were observed. PDGF-BB (1­15 µg/kg iv) significantly improved the hemodynamics and blood perfusion to vital organs (liver and kidney) as well as vascular reactivity and improved the animal survival in hemorrhagic shock rats. PDGF recovering shock-induced vascular hyporeactivity depended on the integrity of the endothelium and myoendothelial gap junction. Cx43 antisense oligodeoxynucleotide abolished these improving effects of PDGF, whereas Cx40 oligodeoxynucleotide did not. Further study indicated that PDGF increased the activity of Rho kinase and PKC as well as vascular Ca2+ sensitivity, whereas it did not interfere with the intracellular Ca2+ concentration in hypoxia-treated vascular smooth muscle cells. In conclusion, systemic application of PDGF-BB may exert beneficial effects on hemorrhagic shock, which are closely related to the improvement of vascular reactivity and hemodynamics. The improvement of PDGF-BB in vascular reactivity is vascular endothelium and myoendothelial gap junction dependent. Cx43, Rho kinase, and PKC play very important role in this process. These findings suggest that PDGF may be a potential measure to treat acute clinical critical diseases such as severe trauma, shock, and sepsis.