Tight Bounds on Pauli Channel Learning without Entanglement.

Quantum entanglement is a crucial resource for learning properties from nature, but a precise characterization of its advantage can be challenging. In this Letter, we consider learning algorithms without entanglement to be those that only utilize states, measurements, and operations that are separable between the main system of interest and an ancillary system. Interestingly, we show that these algorithms are equivalent to those that apply quantum circuits on the main system interleaved with mid-circuit measurements and classical feedforward. Within this setting, we prove a tight lower bound for Pauli channel learning without entanglement that closes the gap between the best-known upper and lower bound. In particular, we show that Θ(2^{n}ϵ^{-2}) rounds of measurements are required to estimate each eigenvalue of an n-qubit Pauli channel to ϵ error with high probability when learning without entanglement. In contrast, a learning algorithm with entanglement only needs Θ(ϵ^{-2}) copies of the Pauli channel. The tight lower bound strengthens the foundation for an experimental demonstration of entanglement-enhanced advantages for Pauli noise characterization.

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn's disease.

BACKGROUND: Adalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn's disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn's disease (CD), but implementation is challenging. AIM: To evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn's disease. METHODS: A prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn's disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the  ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients' quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. RESULTS: These investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment  in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05). CONCLUSION: Adalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn's disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Three-Dimensional Microfluidic Chip for Efficient Capture of Secretory Autophagosomes and Sensitive Detection of Their Surface Proteins.

Recent studies on autophagy demonstrated a new extracellular secretion pathway for autophagosomes in addition to the routinely described intracellular degradation pathway. Besides, the secretory autophagosomes were found closely related to the occurrence and development of cancers. Therefore, analysis of the protein expression on secretory autophagosomes is a promising noninvasive strategy for cancer diagnosis and mechanism study. Herein, we constructed a three-dimensional (3D) microfluidic chip employing a fusiform micropillar array and layer-by-layer modification of gelatins, which obviously enhanced the mass transfer between reactants and increased the immobilization sites for capture antibody. As a result, the autophagosome capture efficiency of the 3D chip (74%) is significantly higher than that of the unmodified flat chip (47%). Using a two-step immunoreaction, ovarian cancer cell-secreted autophagosomes were successfully captured and detected. The results showed that two proteins, LC3B and HSP60 at the surface of autophagosomes, can be detected with limits of detection (LODs) of 141 particles µL-1 and 126 particles µL-1, respectively. In addition, both LC3B and HSP60 expressions on autophagosomes can be used to distinguish the serum samples between cancer patients and healthy people, with a p value less than 0.01 (statistically significant difference) or 0.05 (statistically different), respectively. Moreover, the summed signal of LC3B and HSP60 showed a p value less than 0.001 (extremely statistically significant difference), demonstrating the good potential of this chip for further application in cancer diagnosis.

TfR Aptamer Enhanced Blood-Brain Barrier Penetration of Biomimetic Nanocomplexes for Intracellular Transglutaminase 2 Imaging and Silencing in Glioma.

Engineering a versatile nanocomplex integrating effective penetration of the blood-brain barrier (BBB), accurate diagnosis, and boosting therapy has always been an intractable challenge in glioblastoma multiforme (GBM). Herein, biomimetic nanocomplexes (TMPsM) for single intracellular transglutaminase 2 (TG2)-triggered self-assembly imaging and RNAi therapy for GBM are subtly developed. To prove the concept, transferrin receptor (TfR) aptamer-modified brain metastatic tumor cell membrane is prepared as the shell for dual BBB targeting capability and prolonged blood retention time. Upon targeting entering into GBM, hollow MnO2 is decomposed to release KKGKGQQ-tetraphenylethene (Pep-TPE) and siRNA. Owing to TG2 dependence, the non-emissive Pep-TPE would be self-aggregated to induce the emission turn-on in GBM that contain overexpressed TG2. The resulting aggregation-induced emission fluorescence imaging with a high signal-to-noise ratio can achieve the precise localization of the tumor and dynamic detection of TG2 activity, thereby allowing the GBM accurate diagnosis. Notably, the TG2 can be silenced by the released siRNA to cause cell apoptosis and increase chemotherapeutic sensitivity, ultimately realizing excellent antitumor efficacy. In vitro and in vivo results demonstrate that the as-prepared TMPsM indeed possess superior BBB penetration, precise diagnosis, and effective therapy of GBM. The proposed strategy may pioneer a new path for the theranostics of brain tumors.

Inhibition of Alzheimer's Aß1-42 Fibrillogenesis and Removal of Copper Ions by Polypeptides Modified Gold Nanoparticles.

Aggregation and fibrillation of ß-amyloid peptides (Aß) as well as accumulation of toxic metal ions have been believed to be the central events to cause Alzheimer's disease (AD). Thus, an attractive therapeutic tactic for AD is to design and synthesize inhibitors and metal chelators to prevent Aß aggregation and chelate toxic metal ions. In this study, the polypeptide functionalized gold nanoparticles (PFGNP) were obtained by modifying polypeptides Cys-Gly-Gly-Gly-Leu-Pro-Phe-Phe-Asp (CGGGLPFFD) and Cys-Gly-Gly-Gly-Gly-Gly-His (CGGGGGH) onto gold nanoparticles through gold-sulfur bond. The inhibitory properties of PFGNP toward Aß1-42 fibril formation was assessed by thioflavin T (ThT) fluorescence method and corroborated by atomic force microscopy analysis. The ability of PFGNP to complex copper ions was studied by electrochemical method. The experimental results reveal that PFGNP can effectively chelate copper ions and significantly inhibit the fibrillation of Aß1-42 . Moreover, PFGNP exhibits significantly protective effect on Aß-induced cytotoxicity toward human neuroblastoma SH-SY5Y cells.

First report of Bougainvillea spectabilis Willd bacterial leaf spot caused by Pantoea stewartii subspecies indologenes in China.

Bougainvillea spectabilis Willd. is an important ornamental flowering plant belonging to the family Nyctaginaceae. It is widely used in landscape designs in tropical and subtropical regions. In December 2020, severe disease-causing leaf spots were discovered on the leaves of B. spectabilis in the Modern Agricultural Park (110°19' E, 21°26' N) Zhanjiang City, Guangdong Province, China. Field surveys revealed that the disease was widespread, with an incidence of 60-80%. Early symptoms on the leaves appeared as tiny leaf spots that later developed into concentric circles surrounded by a yellowish halo (Fig. 1). Diseased leaves with typical symptoms were collected for pathogen isolation. The leading edges of the lesions were excised, sanitized in 75% ethanol for 30 s and in 3% sodium hypochlorite for 3 min, and rinsed three times with sterile distilled water (SDW). The diseased tissue was crushed in 1 mL SDW, soaked for 15 min, and then spread onto nutrient agar medium on a petri dish. Circular, bright yellow colonies with smooth margins were observed after 24 h of incubation at 28 °C. The isolate (SJM1) was a gram-negative bacillus with positive results for catalase, indole synthesis, maltose, and arbutin and negative results for sorbitol, lactose, salicin, and starch hydrolysis. The SJM1 genomic DNA was extracted using the TIANamp Bacterial DNA Kit, and partial 16S rDNA gene segments were amplified using the bacterial generic primers 27F and 1492R. The collated 16S rDNA gene sequences were submitted to the NCBI GenBank (MZ723935). BLAST analysis of the sequences revealed 99.38% identity with Pantoea stewartii (MG517424.1). Amplification using subspecies-specific primers galE (#562/564; Gehring et al. 2014), glmS (#356/341; Wensing et al. 2010), and pstC + pstS (#338/339; Wensing et al. 2010) revealed that the genes showed 99-100% identity with P. stewartii subsp. indologenes (galE = 100%, MZ754494.1; glmS = 99.79%, MZ75496.1; and pstC + pstS = 99.89%, MZ754495.1). Phylogenetic trees were constructed using the neighbor-joining method (MEGA X), with both the 16S rDNA sequence (Fig. 2 2A) and the concatenated 16S rDNA, galE, pstC + pstS, and glmS sequences (Fig.2 2B). The SJM1 isolate belonged to the same clade as P. stewartii subsp. indologenes and was 99% homologous to P. stewartii subsp. indologenes strain ZJ-FGZX1 (Fig. 2 2B; Ren et al. 2020). Pathogenicity tests were performed through prick wound inoculation. Sterile needles were used to create fresh wounds on healthy young leaves of one-year-old B. spectabilis plants. Wounds were inoculated with 20 µl bacterial suspension (1 × 108 CFU/ml) or SDW. Four leaves per plant and three plants per treatment were evaluated. The plants were incubated at 28 °C temperature and 80-90% relative humidity. After 4-7 days of inoculation, all plants inoculated with the bacterial suspension had spot symptoms with a halo, similar to those observed in the field. However, leaves inoculated with SDW alone did not show any symptoms. Furthermore, the colony morphology and 16S rDNA sequences of the strains isolated from the inoculated leaves were identical to those of the original isolates. These results verified Koch's postulates. Based on biochemical identification and sequencing analysis, the pathogen causing B. spectabilis leaf spot was identified as P. stewartii subsp. indologenes. Previous reports have shown that P. stewartii subsp. indologenes can cause diseases in Dracaena sanderiana, Cenchrus americanus, and Allium cepa (Zhang et al. 2020, Ashajyothi et al. 2021, Stumpf et al. 2018). To our knowledge, this is the first report of P. stewartii subsp. indologenes causing B. spectabilis leaf spot disease in China.

Cascaded Nanozyme System with High Reaction Selectivity by Substrate Screening and Channeling in a Microfluidic Device.

Surpassing natural enzymes in cost, stability and mass production, nanozymes have attracted wide attention in fields from disease diagnosis to tumor therapy. However, nanozymes intrinsically have low reaction selectivity, which significantly restricts their applications. A general method is reported to address this challenge by following a biomimetic operation principle of substrates channeling and screening. Two oxidase- and peroxidase-like nanozymes (i.e., emerging N-doped carbon nanocages and Prussian blue nanoparticles), were cascaded as a proof of concept to improve the reaction selectivity in transforming the substrate into the targeted product by more than 2000 times. The cascaded nanozymes were also adopted to a spatially confined microfluidic device, leading to more than 100-fold enhancement of the reaction efficiency due to signal amplification.

Quantum Limits of Superresolution in a Noisy Environment.

We analyze the ultimate quantum limit of resolving two identical sources in a noisy environment. We prove that in the presence of noise causing false excitation, such as thermal noise, the quantum Fisher information of arbitrary quantum states for the separation of the objects, which quantifies the resolution, always converges to zero as the separation goes to zero. Noisy cases contrast with noiseless cases where the quantum Fisher information has been shown to be nonzero for a small distance in various circumstances, revealing the superresolution. In addition, we show that false excitation on an arbitrary measurement, such as dark counts, also makes the classical Fisher information of the measurement approach to zero as the separation goes to zero. Finally, a practically relevant situation resolving two identical thermal sources is quantitatively investigated by using the quantum and classical Fisher information of finite spatial mode multiplexing, showing that the amount of noise poses a limit on the resolution in a noisy system.

Investigation of Environmental Pollutant-Induced Lung Inflammation and Injury in a 3D Coculture-Based Microfluidic Pulmonary Alveolus System.

The health impact of environmental pollution involving an increase in human diseases has been subject to extensive study in recent decades. The methodology in biomimetic investigation of these pathophysiologic events is still in progress to uncover the gaps in knowledge associated with pollution and its influences on health. Herein, we describe a comprehensive evaluation of environmental pollutant-caused lung inflammation and injury using a microfluidic pulmonary alveolus platform with alveolar-capillary interfaces. We performed a microfluidic three-dimensional coculture with physiological microenvironment simulation at microscale control and demonstrated a reliable reconstruction of tissue layers including alveolar epithelium and microvascular endothelium with typical mechanical, structural, and junctional integrity, as well as viability. On-chip detection and analysis of pulmonary alveolus responses focusing on various inflammatory and injurious dynamics to the respective pollutant stimulations were achieved in the coculture-based microfluidic pulmonary alveolus model, in comparison with common on-chip monoculture and off-chip culture tools. We confirmed the synergistic effects of the epithelial and endothelial interfaces on the stimuli resistance and verified the importance of creating complex tissue microenvironments in vitro to explore pollution-involved human pathology. We believe the microfluidic approach presents great promise in environmental monitoring, drug discovery, and tissue engineering.

Integrated Microfluidic Device for Accurate Extracellular Vesicle Quantification and Protein Markers Analysis Directly from Human Whole Blood.

Extracellular vesicles (EVs) have the potential to be utilized as disease-specific biomarkers. Although strategies for on-chip isolation and detection of EVs have recently been developed, they need preprocessing of clinical samples and are not accurate enough for disease diagnosis just judging by EVs concentration. Here, we designed an integrated microfluidic device named a plasma separation and EV detection (PS-ED) chip for plasma separation, quantification, and high-throughput protein analysis of EVs directly from clinical whole blood samples. The device included two modules (PS and ED module): the PS module was a six-loop microchannel for rapid separation of plasma from clinical whole blood samples under inertial force; the amount of EVs in the separated plasma kept the same value as in the initial blood samples. The module reduced the mechanical damage to the blood cells and thus reduced the interference of debris or cellular contents from damaged cells during EVs detection; the ED module contained four S-channels for quantification and high-throughput protein analysis of EVs; a wide detection range from 2.5 × 102 to 2.5 × 108 particles/µL with a detection limit of 95 particles/µL was obtained. Through simultanously monitoring three proteins (CD81, CD24, and EpCAM) of EVs, the cancer type can be accurately confirmed. Furthermore, clinical blood sample analysis verified that the proposed device could be used for accurate diagnosis and therapy monitoring of ovarian cancer.

Accurate Cancer Diagnosis and Stage Monitoring Enabled by Comprehensive Profiling of Different Types of Exosomal Biomarkers: Surface Proteins and miRNAs.

Exosomes are recognized as promising biomarkers for early cancer diagnosis and prognosis owing to a large amount of biological information they carried. But the key is that single type of exosomal biomarker analysis is not sufficient enough for accurate cancer diagnosis and stage monitoring due to the insufficient information and high false positive signal. To address the challenge, here simultaneous in situ detection of different types of exosomal biomarkers (surface proteins: CD81, ephrin type-A receptor 2, and carbohydrate antigen 19-9; miRNAs: miR-451a, miR-21, and miR-10b) is conducted with a 3D microfluidic chip, which works in conjunction with quantum dot (QD) labeling and vesicle fusion technology. After exosomes are efficiently captured by the microfluidic chip, the quantification of multiple exosomal proteins is achieved by using three kinds of QDs with the same excitation and different emission wavelengths, and virus-mimicking fusogenic vesicles encapsulating three exquisitely engineered molecular beacons are introduced for ultrasensitive detection of multiple exosomal miRNAs without requiring RNA extraction. Through comprehensive profiling different types of exosomal biomarkers, the false positive rate is substantially avoided and the accuracy of cancer diagnosis and stage monitoring is improved to ≈100%, which are critical to cancer effective treatment and favorable prognosis.

Ancilla-Free Quantum Error Correction Codes for Quantum Metrology.

Quantum error correction has recently emerged as a tool to enhance quantum sensing under Markovian noise. It works by correcting errors in a sensor while letting a signal imprint on the logical state. This approach typically requires a specialized error-correcting code, as most existing codes correct away both the dominant errors and the signal. To date, however, few such specialized codes are known, among which most require noiseless, controllable ancillas. We show here that such ancillas are not needed when the signal Hamiltonian and the error operators commute, a common limiting type of decoherence in quantum sensors. We give a semidefinite program for finding optimal ancilla-free sensing codes in general, as well as closed-form codes for two common sensing scenarios: qubits undergoing dephasing, and a lossy bosonic mode. Finally, we analyze the sensitivity enhancement offered by the qubit code under arbitrary spatial noise correlations, beyond the ideal limit of orthogonal signal and noise operators.

Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice.

1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters. 2. In vitro uptake tests showed that jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 µM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1-1 µM (for OCT2 and OCT3) and 1-10 µM (for PMAT). 3. In mouse synaptosomes, jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant. 4. The antidepressant-like action of jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of jatrorrhizine (5, 10 and 20 mg/kg, i.p.) or venlafaxine (20 mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group. 5. The concentration of jatrorrhizine shows a dose-dependent increase in brain tissues. 6. Our study suggested that jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters.

Sensorimotor Cortical Neuroplasticity in the Early Stage of Bell's Palsy.

Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brain's ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bell's palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations.

Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir.

Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 µM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption.

Interaction of six protoberberine alkaloids with human organic cation transporters 1, 2 and 3.

1. Organic cation transporters (OCTs) play an important role in drug safety and efficacy. Protoberberine alkaloids are ubiquitous organic cations or weak bases with remarkable biological actives. This study was to elucidate the potential interaction of alkaloids (coptisine, jatrorrhizine, epiberberine, berberrubine, palmatine and corydaline) with OCTs using Madin-Darby canine kidney (MDCK) cells stably expressing human OCT1, OCT2 and OCT3. 2. All the tested alkaloids significantly inhibited the uptake of MPP(+), a model OCT substrate, in MDCK-hOCTs cells with the IC50 of 0.931-9.65 µM. Additionally, coptisine, jatrorrhizine and epiberberine were substrates of all the hOCTs with the Km of 0.273-5.80 µM, whereas berberrubine was a substrate for hOCT1 and hOCT2, but not for hOCT3, the Km values were 1.27 and 1.66 µM, respectively. The transport capacity of coptisine in MDCK cells expressing the variants of hOCT1-P341L or hOCT2-A270S was significantly higher than that in wild-type (WT) cells with the Clint (Vmax/Km) of 379 ± 7.4 and 433 ± 5.7 µl/mg protein/min, respectively. 3. The above data indicate that the tested alkaloids are potent inhibitors, and coptisine, jatrorrhizine, epiberberine and berberrubine are substrates of hOCT1, hOCT2 and/or hOCT3 with high affinity. In addition, the variants (OCT1-P341L and OCT2-A270S) possess higher transport capacity to coptisine than WT hOCTs.

Effect of temperature on oxidative stress, antioxidant levels and uncoupling protein expression in striped hamsters.

According to the rate of living-free radical hypothesis, higher metabolic rates should increase reactive oxygen species (ROS) production. However, the "uncoupling to survive" hypothesis postulates that uncoupling proteins (UCPs) can decrease ROS production by lowering the potential of the inner mitochondrial membrane, in which case the correlation between metabolic rate and ROS levels would be a negative rather than positive. In this study, we examined energy intake, oxidative stress levels, antioxidant activity and the expression of UCPs in brown adipose tissue (BAT), and in the liver, heart, skeletal muscle and brain, of striped hamsters (Cricetulus barabensis) acclimated to either 5 °C or 32.5 °C. The energy intake of hamsters acclimated to 5 °C increased by 70.7%, whereas the energy intake of hamsters acclimated to 32.5 °C decreased by 31.3%, relative to hamsters kept at room temperature (21 °C) (P<0.05). Malonadialdehyde (MDA) levels, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity in BAT significantly decreased in 5 °C group, but increased in 32.5 °C group, relative to the 21 °C group. Neither ROS levels (i.e. H2O2 levels), nor antioxidants in skeletal muscle, liver, heart or brain tissue, were affected by temperature. UCP1 expression in BAT was significantly up-regulated in 5 °C group, but down-regulated in 32.5 °C group, relative to the 21 °C group. UCP3 expression of skeletal muscle was also up-regulated significantly in hamsters acclimated to 5 °C. These results suggest that the relationship between ROS levels and metabolic rate was negative, rather than positive. UCP1 expression in BAT may have played a role in lowering ROS levels.

Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

[Effect of shenfu injection on CYP450s of rat liver].

The paper is to report the study of the effect of Shenfu injection on the enzyme activity of liver CYP450 and its mRNA level of rat liver. Microsome of rat liver was prepared after intravenous administration of Shenfu injection for 7 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA expression of CYP1A2, CYP2B1/2, CYP2C11 and CYP3A1 in the liver was detected by RT-PCR. Shenfu injection obviously induced the enzyme activities of CYP2B and CYP2C. Meantime Shenfu injection decreased the enzyme activities of CYP1A2 and CYP3A. The mRNA levels of CYP2B and CYP2C were also induced in rats treated with Shenfu injection. But it obviously inhibited the mRNA level of CYP1A2 and CYP3A. Since the enzyme activity and mRNA level were obviously changed after administration, the potential effect of drug-drug interaction should be concerned.