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Human epidermal growth factor receptor 2 (HER2) overexpression and activation are crucial for trastuzumab resistance in HER2-positive breast cancer; however, the potential regulatory mechanism of HER2 is still largely undetermined. In this study, a novel circular RNA derived from peptidylprolyl isomerase D (PPID) is identified as a negative regulator of trastuzumab resistance. Circ-PPID is highly stable and significantly downregulated in trastuzumab-resistant cells and tissues. Restoration of circ-PPID markedly enhances HER2-positive breast cell sensitivity to trastuzumab in vitroand in vivo. Circ-PPID directly binds to N-acetyltransferase 10 (NAT10) in the nucleus and blocks the interaction between NAT10 and HER2 mRNA, reducing N4-acetylcytidine (ac4C) modification on HER2 exon 25, leading to HER2 mRNA decay. Intriguingly, the subcellular localization of circ-PPID differs between trastuzumab-sensitive and -resistant cells. Circ-PPID in trastuzumab-resistant cells is located more in the cytoplasm, mainly due to the upregulation of Exportin 4 (XPO4), which results in the loss of spatial conditions for circ-PPID to bind to nuclear NAT10. Taken together, our data suggest that circ-PPID is a previously unappreciated ac4C-dependent HER2 epigenetic regulator, providing a promising therapeutic direction for overcoming trastuzumab resistance in clinical setting.

High-gradient aspheric elements need to meet the requirements of both high-gradient aspheric characteristics and a streamlined shape in aerodynamics. The shape characteristics of high-gradient aspheric surfaces bring great challenges to machining. Aiming at hard machinability of single-point diamond turning high-gradient optical opponents, an ultraprecision XZBaxes single-point diamond turning technique was presented based on rotation B-axis platform. Through analysing the traditional XZaxes turning method, the new XZBaxes turning process was proposed to fabricate a high-gradient aspheric surface. The influences of setting errors and cutting edge of arc lathe tool in Y-direction and X-direction on profile accuracy were analysed for correcting the new tool position. The compensation turning method of axisymmetric surface was presented. An error compensation turning experiment of copper was proposed and carried out to obtain a high-gradient aspheric surface. After three time cycles, the profile accuracy was improved from PV590 nm to PV103 nm.

The emerging business models have impelled firms’ competition in a brand-new and fast-growing market. This study examines such a competition for market share through advertising and loyalty reward programs. Two stages can be distinguished based on the transformation of the competition strategies. These stages can be formulated as a dynamic differential game model and a static Hotelling game model. The operation strategies and performances of two firms are determined and compared viaanalytical studies and case analyses toward a bicycle-sharing program, i.e., Ofo versusMobike. Historical data are used to fit the curve of the market size and to estimate the parameter values of these models. The results show that during the first stage, the difference in market share between these firms gradually decreases (increases) when the advertising response constant is low (high). Meanwhile, in the second stage, these firms offer converse reward strategies.

Superhydrophobic surfaces with microstructures and multifunctionality have attracted intense research interest. Herein, a multiscale microflower structured surface (MMSS) was successfully fabricated by electrostatic air spray. To systematically study the preparation process, the influences of different electrostatic voltages, solution ratios, soaking time, spray distances, and spray time on surface morphology and hydrophobicity were analyzed. The surface has good superhydrophobic properties with a water contact angle of 162.3°, which allows the surface to be self-cleaning and antifouling. The surface hydrophobicity can be maintained after various mechanical and chemical damages. To overcome the limitation that existing droplet manipulation relies on special materials and surfaces, a new and universal droplet transport method is presented to successfully perform nondestructive droplet manipulations, which relies on external forces and droplet deformation to drive droplets. Therefore, this paper represents a different approach from previous studies of superhydrophobic surfaces and provides a new way to achieve dynamic droplet manipulations. These results indicate that the multifunctional MMSS will be widely used in industrial droplet transportation and self-cleaning applications.

Methane (CH4) oxidation driven by soil aerobic methanotrophs demonstrates the capacity of grassland as a CH4sink. In this study, we compared the oxidation characteristics of atmospheric‐level and elevated concentration (10%) CH4in a typical grassland (steppe) on the Loess Plateau, an alpine meadow (meadow) on the Qinghai‐Tibet Plateau, and an inland arid‐area artificial grassland (pasture) in northwest China and investigated the communities of active methanotrophs and their contribution to CH4oxidation using DNA‐based stable‐isotope probing and Illumina Miseq sequencing. The results showed that the oxidation of atmospheric CH4only occurred in steppe and meadow soils where the USCγ group of methanotrophs was numerically dominant in the methanotroph community. Pasture soils, with their very low relative abundance of USCγ, did not show atmospheric CH4oxidation. However, a DNA‐stable isotope probing experiment with 10% CH4indicated that conventional CH4oxidizers (Methylocaldumand Methylocystis) rather than USCγ communities assimilated significant amounts of 13CH4for growth. The CH4oxidation mechanisms in the three experimental grassland soils varied significantly. The USCγ group may be obligate oligotrophic microorganisms or their growth requires specific unknown conditions. Grassland soils are methane (CH4) sinks, but their capacities vary between grassland types. In this study, atmospheric CH4consumption occurred in steppe and meadows but not in pasture. All three soils consumed elevated CH4. Methanotroph community differences between the three soils explain the variation in CH4consumption.

Friction and wear test equipment, scanning electron microscope, abrasion balls made of CGr15 high carbon chromium bearing steel, and liners made of NM500 steel were used for wear simulation and friction–wear experiments. The variation trends of friction coefficient, wear amount, and sub-surface characteristics under dry friction and slurry conditions were studied. Simulations supported the research results. The results show that the pressure and the coefficient of friction vary inversely. The coefficient of friction between the abrasive ball and the lining plate decreases with the increase of the load. Samples subjected to a pressure of 120N have higher values of Kernel Average Misorientation (KAM) and lower recrystallization ratios compared to samples subjected to a pressure of 130N. In a slurry environment, the difference in wear surface depth decreases to 0 μm (120N) and 5 μm (130N). This change indicates that the presence of the slurry alters the wear characteristics of the surfaces, leading to a reduction in the depth difference between the surfaces under different load conditions. This observation highlights the importance of considering the influence of the slurry environment on friction and wear behavior in simulations and experiments.

Inducing shale reservoir resonance is an environmentally friendly and efficient unconventional oil/gas production technology. It is necessary to study the effect of resonance on shale physical parameters. This paper clarifies the resonance mechanism of improving shale reservoirs and constructs the natural frequency parameter equation under a single excitation direction using vibration system theory and rock mechanics. The resonance experiment is carried out after the physical parameters of the shale and coal samples are verified by material characterization technology. Meanwhile, CT scanning technology and matrix permeability tests are used to measure the samples’ pore development and permeability changes. Eventually, the coalbed methane field in Qinshui Basin, Shanxi province, was selected as the experimental object for the reservoir resonance test. We analyzed the production data of the test wellhead. The results indicate that the mechanism of resonance improvement of shale physical parameters promotes the redevelopment of primary cracks in the rock mass; the porosity and permeability of rock mass are increased by 2–12 times and 2–8 times, respectively, after the once resonance test. The CBM (coalbed methane) wells whose productivity is in a state of decay have been significantly enhanced after resonance stimulation, and the relative daily gas production is increased by 101.61%.

In two-stage zinc pressure leaching process, zinc calcine is used to neutralize the acid pressure leaching solution. The residue usually contains a certain amount of zinc, iron, and other elements. The dissolved iron usually affects the mineral leaching and impurity removal as well as solution purification process. However, the behaviors of iron oxidation and migration are not fully understood and those behaviors impact zinc recovery from the residue. Thus, the behaviors of zinc and iron in the neutralized residue during pressure and hot acid leaching were investigated for varying temperature, acidity, leaching time, and oxygen partial pressure. The results showed that acid to zinc mole ratio is the key factor for the extraction process, and the zinc extraction rate accelerates with an increase in solution acidity. At temperature 150 °C, acid to zinc mole ratio 2.7, residence time 2 h, and oxygen partial pressure 0.6 ~ 0.7 MPa, the zinc extraction rate can reach 98.0%. The iron extraction, however, varied: (A) it increased with temperature and then decreased and (B) displayed an initial increase followed by a decrease with respect to the leaching time. In actual production, iron in marmatite and pyrrhotite is leached into solution and then oxidized and precipitated into residue as hematite or ferrovanadium. In order to achieve the decomposition of ferrite in the neutralized residue, a high initial acidity is essential.

Nerve infiltration in the tumor microenvironment is emerging as a promoter of cancer progression that could be targeted in therapies, but the mechanisms initiating tumor innervation remain to be elucidated. Here we report that endoplasmic reticulum (ER) stress in cancer cells is transmitted to neuronal cells, resulting in neurite outgrowth and tumor innervation. In vitro, the induction of ER stress in various human cancer cells resulted in the synthesis and release of the precursor for brain-derived neurotrophic factor (proBDNF) through a mechanism dependent on the transcription factor X-box binding protein 1 (XBP1). Cancer cell-released proBDNF was found to mediate the transmission of ER stress to neurons, resulting in the stimulation of neurite outgrowth. Next-generation sequencing indicated the increased expression of the Egl-9 family hypoxia inducible factor 3 (EGLN3) that was mediated by c-MYC and necessary to neurite outgrowth induced by proBDNF. In orthotopic tumor xenograft, ER stress stimulated XBP1 and proBDNF expression as well as tumor innervation. Anti-proBDNF antibody inhibited both tumor innervation and cancer progression induced by ER stress. Interestingly, the chemotherapeutic drug 5-Fluorouracil (5-FU) was found to induce ER stress and tumor innervation, and this effect was inhibited by anti-proBDNF antibody. Finally, in human tumors, cancer tissues with nerve infiltration expressed high XBP1 and proBDNF while EGLN3 was upregulated in infiltrated nerves. This study reveals that ER stress participates in tumor innervation through the release of proBDNF and that targeting this pathway could be used in future therapies.

This study was aimed to evaluate the effect of vitamin E (VE) on laying performance, VE deposition, antioxidant capacity, immunity, follicle development, estrogen secretion, ovary metabolome, and cecal microbiota of laying hens. One hundred and twenty XinYang Black-Feathered laying hens (70 wk old) were randomly assigned to 2 groups (6 replicates of 20 birds), and fed a basal diet (containing 20 mg/kg VE, control (CON) group) and a basal diet supplemented with 20 mg/kg VE (VE group). The experiment lasted for 10 wk. Results showed that VE supplementation increased laying performance, antioxidant capacity, and immunity, as evidenced by increased (P< 0.05) performance (laying rate), antioxidant (glutathione peroxidase, total superoxide dismutase, total antioxidant capacity, and catalase) and immune (immunoglobulins) parameters, and decreased (P< 0.05) feed/egg ratio and malondialdehyde. Meanwhile, VE group had higher (P< 0.05) pregrade follicles, ovary index and serum estrogen levels than CON group. 16S rRNA sequencing showed that VE supplementation altered the cecal microbiota composition by increasing Bacteroides, Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG-001and Megamonasabundances andreducing Christensenellaceae_R-7_groupabundance (at genus level), which are mainly associated with the production of short-chain fatty acids. Metabolomic profiling of the ovary revealed that the major metabolites altered by VE supplementation were mainly related to follicle development, estrogen secretion, anti-inflammatory, antioxidant, phototransduction, bile acid synthesis, and nutrient transport. Furthermore, changes in cecal microbiota (at genus level) and ovary metabolites were highly correlated with laying performance, antioxidant, and immune parameters. In summary, VE contributed to the laying performance of aged laying hens by enhancing antioxidant, immune, and ovarian functions, promoting follicle development and estrogen secretion, and regulating gut microbiota and ovary metabolites. These findings will provide a new perspective on the mechanisms of egg production in aged poultry ovaries.

To guide the design of novel graphene-based catalysts in catalytic ozonation for micropollutant degradation, the mechanism of catalytic ozonation with heteroatom-doped graphene was clarified. Reduced graphene oxide doped with nitrogen, phosphorus, boron, and sulfur atoms (N-, P-, B-, and S-rGO) were synthesized, and their catalytic ozonation performances were evaluated in the degradation of refractory organics and bromate elimination simultaneously. Doping with heteroatoms, except sulfur, significantly improved the catalytic ozonation activity of graphene. Introducing sulfur atoms destroyed the stability of graphene during ozonation, with the observed partial performance improvement caused by surface adsorption. Degradation pathways for selected refractory organics were proposed based on the intermediates identified using high-resolution Orbitrap mass spectroscopy and gas chromatographic–mass spectroscopy. Three and six new unopened intermediates were identified in benzotriazole and p-chlorobenzoic acid degradation, respectively. Roles of chemical functional groups, doped atoms, free electron, and delocalized π electron of heteroatom-doped graphene in catalytic ozonation were identified, and contributions of these active centers to the formation of reactive oxygen species (ROS), including hydroxyl radicals, superoxide radicals, singlet oxygen, and H2O2, were evaluated. A mechanism for catalytic ozonation by heteroatom-doped graphene was proposed for the first time.

Missense mutations in the gasdermin-A3 (Gsdma3) gene are associated with skin inflammation and hair loss in mice. However, the physiological function of Gsdma3remains unclear. Herein, we reported that mice carrying the Gsdma3Y344H mutation that encodes a presumptive activated form of Gsdma3 show increased heat production along with lower body fat percentages. Detailed analysis indicated that this metabolic phenotype is mediated by serum IL-6–induced up-regulation of thermogenesis in brown adipose tissue. The mutant form of Gsdma3 promotes the expression of IL-6 in the epidermis in a c-Jun N-terminal kinase (JNK) signaling–dependent manner. The higher whole-body heat production in alopecia and excoriation mice could be suppressed by an IL-6 receptor/GP130 inhibitor. Our results uncovered Gsdma3/IL-6–dependent cross talk between the skin and brown adipose tissue.

Large artery atherosclerosis and cardioembolism are the two major subtypes of ischemic stroke. We herein describe a 75-year-old man with acute complete cerebral infarction in the typical territories of the bilateral anterior cerebral artery (ACA) and left middle cerebral artery. Brain magnetic resonance angiography showed that the right A1 segment of the ACA was affected by severe arteriosclerosis and that the right ACA other than the A1 segment was compensated by the left ACA through the anterior communicating artery. Acute cardioembolism only occluded the left anterior circulation but simultaneously blocked the right ACA due to decompensation. We presume that the bilateral cerebral infarctions were caused by chronic atherosclerosis and acute cardioembolism.

Chronic active Epstein–Barr virus infective enteritis (CAEBV enteritis) is rare and has not been well described yet. Therefore, we reported the clinicopathologic features of 11 patients with chronic active Epstein–Barr virus infective enteritis and their differences from inflammatory bowel disease. The major clinical presentations of chronic active Epstein–Barr virus infective enteritis were intermittent fever over 39 °C (100%), diarrhea (73%), abdominal pain (64%), lymphadenopathy (64%), splenomegaly (64%), and hepatomegaly (27%). The main endoscopic findings included numerous shallow, small, and irregular ulcers, mainly involving colon and small intestine together, no cobble-like appearance, and longitudinal ulcers. Compared to inflammatory bowel disease patients, the frequency of intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, the value of C-reactive protein, and serum Epstein–Barr virus DNA (EBV DNA) were significantly higher in chronic active Epstein–Barr virus infective enteritis patients (p< 0.01). The histologic findings show transmural inflammation with extended lymphoid infiltration, fissuring ulcers, and intraepithelial lymphocytosis. But chronic active Epstein–Barr virus infective enteritis lacked granulomas and connective tissue changes such as neural hypertrophy and thickened muscularis mucosae. Three chronic active Epstein–Barr virus infective enteritis patients died within 5 years of disease onset, and those three patients have received total colectomy, two of them died within 1 month after surgery. In this study, clinicopathologic features have been summarized to better recognize chronic active Epstein–Barr virus infective enteritis. There are resemblances between chronic active Epstein–Barr virus infective enteritis and inflammatory bowel disease, but some symptoms, signs, and indexes like intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, and elevated C-reactive protein, Epstein–Barr virus DNA are characteristics to differentiate chronic active Epstein–Barr virus infective enteritis and inflammation. Histopathological features also help the discrimination. Serum Epstein–Barr virus DNA and intestinal tissue in situ hybridization for Epstein–Barr virus-encoded RNA are recommended to exclude chronic active Epstein–Barr virus infective enteritis.

Chronic active Epstein–Barr virus infective enteritis (CAEBV enteritis) is rare and has not been well described yet. Therefore, we reported the clinicopathologic features of 11 patients with chronic active Epstein–Barr virus infective enteritis and their differences from inflammatory bowel disease. The major clinical presentations of chronic active Epstein–Barr virus infective enteritis were intermittent fever over 39 °C (100%), diarrhea (73%), abdominal pain (64%), lymphadenopathy (64%), splenomegaly (64%), and hepatomegaly (27%). The main endoscopic findings included numerous shallow, small, and irregular ulcers, mainly involving colon and small intestine together, no cobble-like appearance, and longitudinal ulcers. Compared to inflammatory bowel disease patients, the frequency of intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, the value of C-reactive protein, and serum Epstein–Barr virus DNA (EBV DNA) were significantly higher in chronic active Epstein–Barr virus infective enteritis patients (p< 0.01). The histologic findings show transmural inflammation with extended lymphoid infiltration, fissuring ulcers, and intraepithelial lymphocytosis. But chronic active Epstein–Barr virus infective enteritis lacked granulomas and connective tissue changes such as neural hypertrophy and thickened muscularis mucosae. Three chronic active Epstein–Barr virus infective enteritis patients died within 5 years of disease onset, and those three patients have received total colectomy, two of them died within 1 month after surgery. In this study, clinicopathologic features have been summarized to better recognize chronic active Epstein–Barr virus infective enteritis. There are resemblances between chronic active Epstein–Barr virus infective enteritis and inflammatory bowel disease, but some symptoms, signs, and indexes like intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, and elevated C-reactive protein, Epstein–Barr virus DNA are characteristics to differentiate chronic active Epstein–Barr virus infective enteritis and inflammation. Histopathological features also help the discrimination. Serum Epstein–Barr virus DNA and intestinal tissue in situ hybridization for Epstein–Barr virus-encoded RNA are recommended to exclude chronic active Epstein–Barr virus infective enteritis.

As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H2O2or relatively high pH value for Fenton reaction‐dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid‐based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction‐independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG2K‐DSPE‐modified liposomes (Lip@SF&FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe2+, and subsequently the formed iron redox pair (Fe2+/Fe3+) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction‐independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor‐killing ability with negligible side effect. Consequently, this two‐pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy. An efficient lipid‐based delivery system is constructed with unsaturated lipids, mPEG2K‐DSPE, oxidation catalyst, and Gpx4 inhibitor sorafenib. While iron redox couple‐catalyzed lipid peroxidation increases the production of lipid peroxide (LPO), Gpx4 inhibitor decreases the reduction of LPO. This work introduces a novel approach for amplifying Fenton reaction‐independent ferroptosis by the bidirectional regulation of LPO accumulation for cancer therapy.

Background: Previous studies have reported that polymorphisms in the interleukin-1 gene may be involved in tumorigenesis and tumor progression.Aim: The purpose of the present study was to evaluate whether an insertion/deletion polymorphism, rs3783553, located in the miR-122 target gene interleukin-1α, was associated with the risk of colorectal cancer.Methods: Genomic DNA was extracted from peripheral venous blood of 382 patients with colorectal cancer and 433 controls, and the polymorphism was genotyped using a polymerase chain reaction assay.Results: Significantly decreased colorectal cancer risk was observed to be associated with the interleukin-1α rs3783553 insertion/insertion genotype (P=0.0001; OR=0.41; 95% CI 0.26, 0.65) and the insertion allele (P<0.001; OR=0.68; 95% CI 0.55, 0.83). Stratification analysis based on clinical and pathological features also revealed that the “TTCA” insertion allele of rs3783553 contributes to slow the progression of colorectal cancer.Conclusion: These results suggest that the rs3783553 polymorphism could be a useful genetic marker to predict the size/extent of colorectal cancer.

During the zinc electrowinning process, fluorine (F) and chlorine (Cl) ions can cause corrosion of the anode plate and difficulty in stripping the zinc cathode sheet. Because of the increasing use of F/Cl in zinc concentrate in industrial production and the stricter requirements of large-size cathode technology (LARCATH), it is very important to remove F and Cl fully from the zinc sulfate solution. In this paper, tests for removing F/Cl in zinc sulfate solution from zinc plant are carried out by the goethite method. The effects of several factors on the removal of Fe, F, and Cl are studied, including the temperature, flow rate of the zinc sulfate solution, pH value, initial iron concentration, and F and Cl concentrations in the zinc sulfate solution. It can be determined from the experimental results that the removal efficiency of F and Cl can reach 26.4 and 38.6%, respectively, under the conditions of 90 °C, pH value 2.75, and flow rate 3.8 mL/min. The removal rate of F ions is mainly related to the amount of lime milk, whereas the pH value has the greatest impact on the removal rate of Cl. The concentration of negative ions on the surface of goethite increases with increasing pH, which is harmful to the absorption of Cl.

The use of different methods for the processing of ginseng can result in alterations in its medicinal properties and efficacy. White ginseng (WG), frozen ginseng (FG), and red ginseng (RG) are produced using different methods. WG, FG, and RG possess different pharmacological properties.

We calculated the ultralow frequency of the interlayer shear and breathing modes of van der Waals layered materials by the linear chain model. Some vibrational modes of different layers have exactly the same frequency when only the nearest neighbor interactions are considered, agreeing well with the experimental results of multilayer graphene and MoS2. These modes are classified as a series of in-phase families based on their eigenvectors. The frequencies of the in-phase family show self-similarity characteristics. When the second nearest neighbor interactions are taken into account, the constant-frequency characteristic of the in-phase family does not hold any more. This means that the in-phase family behavior can be used to determine the sign and strength of the second nearest neighbor interactions unambiguously and conveniently. These results reveal that the in-phase family behavior and the corresponding self-similarity characteristic are robust properties in van der Waals layered materials.

Modal computation with high precision is an important issue for wave propagation in optical waveguides when the eigenmode expansion method is applied. This numerical study of an open waveguide is accomplished by terminating the unbounded regions with perfectly matched layers. Then, by the differential transfer matrix method (DTMM), two nonlinear relations of modes for the TM case are proposed for complex waveguides with varied refractive indexes along the transverse direction. For the gradually varied waveguides, a higher approximation is provided and some asymptotic formulas of leaky modes are created, which may be used as better initial values for some iteration methods. Numerical examples illustrate that our treatment is highly feasible and effective.

In order to solve the problem that CCDs cannot measure the full spectral range in a single measurement, we propose a new wavelength-fitting algorithm that combines the polynomial algorithm applied to the fixed grating with grating equation without CCD or spectrum assembling. Both the grating rotating angle and pixel coordinate of the CCD are written in our wavelength-fitting function. With the calibration of the 576.96 and 579.07 nm mercury spectral line, we can determine that wavelength error of 576.96 nm is between 0.002 and 0.1 nm and wavelength error of 579.07 nm is between 0.006 and 0.06 nm. The calculation results show that the new algorithm can gain more precise wavelength accuracy without a complex assembling operation.

The genus of Forsythia (Oleaceae), composing ca. 10˜15 species, is mostly native to eastern Asia and used in oriental traditional medicines. Phytochemical investigations on Forsythia species have shown that triterpenoids, lignans, flavonoids, phenylethanoid glycosides and C6-C2 natural alcohols, accumulated mainly in the fruits, are the major components. Many studies have elucidated that phenolic compounds, including lignans, phenylethanoid glycosides and flavonoids are responsible for the various biological activities of the herbal medicine. This review lists 141 chemical constituents as well as their biosynthetic pathway, bioactivities and quality control as reported until September, 2011 (104 references).

Abstract: The cytochrome P450 (CYP) enzymes play the central role in synthesis of endogenous substances and metabolism of xenobiotics. The substitution of single amino acid caused by non-synonymous single nucleotide polymorphism (nsSNP) will lead to the change in enzymatic activity of CYP isozymes, especially the drugmetabolizing ability. CYP-nsSNP is a specialized database focused on the effect of nsSNPs on enzymatic activity of CYPs. Its unique feature lies in providing the qualitative and quantitative description of the CYP variants in terms of enzymatic activity. In addition, the database also offers the general information about nsSNP and compounds that are involved in corresponding enzymatic reaction. The current CYP-nsSNP can be accessible at http://cypdatabase.sjtu.edu.cn/ and includes more than 300 genetic variants of 12 CYP isozymes together with about 100 compounds. In order to keep the accuracy of information within database, all experimental data were collected from the scientific literatures, and the users who conducted research to identify the novel CYP variants are encouraged to contribute their data. Therefore, CYP-nsSNP can be considered as a valuable source for experimental and computational studies of impact of genetic polymorphism on the function of CYPs.

Gene expression is stochastic, and noise that arises from the stochastic nature of biochemical reactions propagates through active regulatory links. Thus, correlations in gene-expression noise can provide information about regulatory links. We present what to our knowledge is a new approach to measure and interpret such correlated fluctuations at the level of single microcolonies, which derive from single cells. We demonstrated this approach mathematically using stochastic modeling, and applied it to experimental time-lapse fluorescence microscopy data. Specifically, we investigated the relationships among LuxO, LuxR, and the small regulatory RNA qrr4 in the model quorum-sensing bacterium Vibrio harveyi. Our results show that LuxR positively regulates the qrr4 promoter. Under our conditions, we find that qrrregulation weakly depends on total LuxO levels and that LuxO autorepression is saturated. We also find evidence that the fluctuations in LuxO levels are dominated by intrinsic noise. We furthermore propose LuxO and LuxR interact at all autoinducer levels via an unknown mechanism. Of importance, our new method of evaluating correlations at the microcolony level is unaffected by partition noise at cell division. Moreover, the method is first-order accurate and requires less effort for data analysis than single-cell-based approaches. This new correlation approach can be applied to other systems to aid analysis of gene regulatory circuits.

Quorum-sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Quantitative information on parameters such as the copy number of particular quorum-sensing proteins should contribute strongly to understanding how the quorum-sensing network functions. Here, we show that the copy number of the master regulator protein LuxR in Vibrio harveyican be determined in vivo by exploiting small-number fluctuations of the protein distribution when cells undergo division. When a cell divides, both its volume and LuxR protein copy number, N, are partitioned with slight asymmetries. We measured the distribution functions describing the partitioning of the protein fluorescence and the cell volume. The fluorescence distribution is found to narrow systematically as the LuxR population increases, whereas the volume partitioning is unchanged. Analyzing these changes statistically, we determined that N= 80–135 dimers at low cell density and 575 dimers at high cell density. In addition, we measured the static distribution of LuxR over a large (3000) clonal population. Combining the static and time-lapse experiments, we determine the magnitude of the Fano factor of the distribution. This technique has broad applicability as a general in vivo technique for measuring protein copy number and burst size.

The genus Valeriana (Valerianaceae) contains over 250 species distributed around the world and used in traditional medicines of many cultures. The main compounds isolated from Valeriana species are essential oils, valerenic acid and its derivatives and iridoids, accumulated mainly in the roots and rhizomes. This review lists 135 chemical constituents as well as their biosynthesis and bioactivity as reported by the end of 2008 (80 references).

We investigated the binding interaction between the bacteriophage λ-repressor CI and its target DNA using total internal reflection fluorescence microscopy. Large stepwise changes in the intensity of the red fluorescent protein fused to CI were observed as it associated with and dissociated from individually labeled single-molecule DNA targets. The stochastic association and dissociation were characterized by Poisson statistics. Dark and bright intervals were measured for thousands of individual events. The exponential distribution of the intervals allowed direct determination of the association and dissociation rate constants (kaand kd, respectively). We resolved in detail how kaand kdvaried as a function of three control parameters: the DNA length L, the CI dimer concentration, and the binding affinity. Our results show that although interactions with nonoperator DNA sequences are observable, CI binding to the operator site is not dependent on the length of flanking nonoperator DNA.

The Raman spectra of barium formate were investigated at room temperature and liquid nitrogen temperature and the infrared absorption and reflection spectra at room temperature. The presence of two crystallographically non-equivalent sets of formate ions in the lattice results in the doubling of the internal modes in the vibrational spectra. The observed high-wavenumber vibrational bands are assigned to the internal vibrations of formate ions. Copyright © 2001 John Wiley & Sons, Ltd.