Search

Catalytic microsweepers with single-iron-atom centers were designed to search for and inhibit Helicobacter pylori using dynamically navigated reciprocating locomotion.

Aggregation plays a critical role in modulating the photophysical process of organic molecules. However, the rational control of the construction of a function-oriented stacking mode for efficient ...

Meiling Jin,1,2,* Wenwen Ren,3,* Weiguang Zhang,2 Linchang Liu,2,4 Zhiwei Yin,2,5 Diangeng Li6 1Department of Nephrology, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Nephrology, Chinese People’s Liberation Army General Hospital, Chinese People’s Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases (2011DAV00088), National Clinical Research Center for Kidney Diseases, Beijing, 100853, People’s Republic of China; 3Department of Nephrology, Beijing Ditan Hospital,Capital Medical University, Beijing, 100015, People’s Republic of China; 4Department of Nephrology, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, 100039, People’s Republic of China; 5College of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 6Department of Academic Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Diangeng LiDepartment of Academic Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaTel/Fax +86 10-85231049Email lidiangeng@126.comZhiwei YinCollege of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; Department of Nephrology, Chinese People’s Liberation Army General Hospital, Chinese People’s Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases (2011DAV00088), National Clinical Research Center for Kidney Diseases, Beijing, 100853, People’s Republic of ChinaTel/Fax +86 10-66937010Email zhiwei_yin@126.comPurpose: This study aimed to explore the underlying mechanisms of Shenyankangfu tablet (SYKFT) in the treatment of glomerulonephritis (GN) based on network pharmacology, machine learning, molecular docking, and experimental validation.Methods: The active ingredients and potential targets of SYKFT were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the targets of GN were obtained through GeneCards, etc. Perl and Cytoscape were used to construct an herb-active ingredient–target network. Then, the clusterProfiler package of R was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We also used the STRING platform and Cytoscape to construct a protein–protein interaction (PPI) network, as well as the SwissTargetPrediction server to predict the target protein of the core active ingredient based on machine-learning model. Molecular-docking analysis was further performed using AutoDock Vina and Pymol. Finally, we verified the effect of SYKFT on GN in vivo.Results: A total of 154 active ingredients and 255 targets in SYKFT were screened, and 135 targets were identified to be related to GN. GO enrichment analysis indicated that biological processes were primarily associated with oxidative stress and cell proliferation. KEGG pathway analysis showed that these targets were involved mostly in infection-related and GN-related pathways. PPI network analysis identified 13 core targets of SYKFT. Results of machine-learning model suggested that STAT3 and AKT1 may be the key target. Results of molecular docking suggested that the main active components of SYKFT can be combined with various target proteins. In vivo experiments confirmed that SYKFT may alleviate renal pathological injury by regulating core genes, thereby reducing urinary protein.Conclusion: This study demonstrated for the first time the multicomponent, multitarget, and multipathway characteristics of SYKFT for GN treatment.Keywords: shenyankangfu tablet, glomerulonephritis, network pharmacology, machine learning, molecular docking

Reducing heat dissipation plays an indispensable role in boosting the magnetothermal effect but has received scant attention. Herein, a magnetothermal aerogel (MA) combining an efficient magnetothermal convertor for heat generation and a highly porous aerogel for reducing heat dissipation is developed. Such a heat confinement MA shows a large thermal resistance and high infrared absorption that can effectively confine the heat by regulating interior thermal conduction and radiation, exhibiting a supramagnetothermal effect. In addition, a waterproof beeswax coated MA achieves negligible heat loss and a supramagnetothermal effect even in high-thermal-diffusion aqueous media. As a proof of concept, a synthesized heat-triggered nitric oxide (NO) precursor is integrated into an MA, and the rapid NO generation (∼22 μM/min) resulting in an antibacterial effect further verifies the supramagnetothermal effect of the MA. This work provides an efficient strategy to promote the magnetothermal effect and offers inspiration for building a heat-triggering system.

Background GPRIN1 may be a novel tumor regulator, but its role and mechanism in tumors are still unclear. Methods First, a pan‐cancer correlation analysis was conducted on the expression and prognosis of GPRIN1 based on the data downloaded from The Cancer Genome Atlas (TCGA) database. Second, the Starbase database was used to predict the upstream miRNAs and lncRNAs of GPRIN1, and the expression analysis, survival analysis, and correlation analysis were performed to screen the microRNA (miRNAs)/long non‐coding RNAs (lncRNAs) that had a correlation with kidney renal papillary cell carcinoma (KIRP) or lung adenocarcinoma (LUAD). Third, the CIBERSORT algorithm was employed to calculate the proportion of various types of immune cells, and then the R packages were used for evaluating the relation between GPRIN1 expression and tumor immune cell infiltration as well as between GPRIN1 and the immune cell biomarker. Finally, the correlation analysis was made on GPRIN1 and immune checkpoints (CD274, CTLA4, and PDCD1). Results The pan‐cancer analysis suggested that GPRIN1 was up‐expressed in KIRP and LUAD, and it correlated with poor prognosis. LINC00894/MMP25‐AS1/SNHG1/LINC02298/MIR193BHG‐miR‐140‐3p was likely to be the most promising upstream regulation pathway of GPRIN1. Upexpression of LINC00894/MMP25‐AS1/SNHG1/LINC02298/MIR193BHG and downexpression of miR‐140‐3p were found relevant with poor outcomes of KIRP and LUAD. GPRIN1 expression was significantly correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoints. Conclusions The competitive endogenous (ceRNA) of miR‐140‐3p‐GPRIN1 axis and its upstream lncRNAs are closely related to KIRP and LUAD, and might affect the prognosis and therapeutic effect of KIRP and LUAD., GPRIN1 is an important prognostic marker for KIRP and LUAD. ncRNA (LINC00894/MMP25‐AS1/SNHG1/LINC02298/MIR193BHG)‐mediated high expression of GPRIN1 correlates with poor prognosis and tumor immune infiltration of KIPR and LUAD.

Taizhou is a typical coastal area in East China where drinking water is mainly supplied by reservoir water. The water quality of the reservoirs may be affected to some extent by human activities an...

To identify the status of the water resources carrying capacity in Taizhou City in China, this paper selected 17 evaluation indicators and used principal component analysis to analyze the factors influencing that capacity. Then, an evaluation model was established to assess the water resources carrying capacity in the same city from 2011 to 2020, and a multiple linear regression model was established to predict the total water consumption from 2021 to 2026. The results show that as Taizhou has constructed a water-saving society, its water resources carrying capacity has gradually increased. From 2021 to 2026, Taizhou's total water consumption is predicted to show a downward trend each year. Based on the comprehensive evaluation and prediction results of water resources carrying capacity, the paper proposed water resources management and control measures for Taizhou, providing scientific support for the rational development and utilization of water resources.

This study explores the prediction of financial time series and adaptive trading based on deep learning neural networks so as to strengthen the international cooperation in agricultural finance. Firstly, related concepts of international cooperation in agricultural finance are introduced, and the long short-term memory (LSTM) is applied in the prediction of financial time. Then, an adaptive trading system is established based on the deep learning and reinforcement learning. Finally, adoption result of the financial prediction model based on LSTM neural network is compared with that of the adaptive trading system proposed through empirical researches. When the Hong Kong Hang Seng Index is predicted by the prediction model based on LSTM neural network, it is found that the mean absolute percentage error in recent years has reached 0.9%, which is superior to other prediction models in predicting the financial time series. The proposed adaptive trading system of financial asset based on deep learning is more reliable and stable than the traditional adaptive trading system. This study provides a theoretical basis for applying the deep learning methods in adaptive trading system, and has important reference value for the free trade zone to promote the international cooperation in agricultural finance.

Abnormal gastric pH (pH > 3) has instructive significance for early diagnosis of various diseases, including cancer. However, for low patient compliance, limited penetration depth, high dependence on physiological function or unsafety issue, in situ noninvasive monitoring gastric pH is challenged. Herein, we developed a hydrogel capsule isolated human serum albumin-manganese complex (HSA-Mn) for in situ magnetic resonance imaging (MRI) gastric pH monitoring for the first time. In this strategy, the rotation motion restriction of Mn2+ after binding to HSA significantly increased the R1 (longitudinal relaxation rate) signal, and its high correlation with protonation imparted the HSA-Mn system sensitive responsiveness to varying pH (R1(pH 7)/R1(pH 1) = 8.2). Moreover, a screw jointed hydrogel capsule with signal confinement and internal standard abilities was designed. Such a nanoporous hydrogel capsule with size selectivity to surrounding molecules enabled a stable and sensitive response to different pH simulated gastric fluid within 0.5 h. In addition, with the unique structural outline and stable MRI characteristics, the capsule could also work as an internal standard, which facilitates the collection of signals and trace of the capsule in vivo. Through validating in a rabbit model, the precise abnormal gastric pH recognition capacity of the HSA-Mn hydrogel capsule was amply confirmed. Hence, the hydrogel capsule isolated HSA-Mn system strategy with great biocompatibility could be expected to be a potent tool for in situ anti-disturbance MRI of gastric pH in future clinical application.

Human activities accelerate global nitrogen (N) deposition, and elevated N availability may alter the stoichiometric balance of nutrients and then affect nutrient absorption by plants. The boreal forest is considered one of the world’s most N-limited ecosystems, and its response to N deposition is already a hot issue. In order to explore how long-term nitrogen addition influences nutrient uptake and distribution in Larix gmelinii in a boreal forest, four N treatment levels (0, 25, 50 and 75 kg N ha−1 yr−1) have been applied in a boreal forest since May 2011. Nitrogen addition significantly reduced the soil pH, significantly changed the soil N availability, increased the total N and N/P in needles and fine roots, and decreased the total P in needles and the C/N in soil. Nitrogen addition significantly reduced nitrogen resorption efficiency, and its impacts on P resorption efficiency were not significant. Nitrogen addition significantly increased the root length, surface area and diameter of 4th- and 5th-order transport fine roots. The N and N/P of needles showed seasonal variation. The needle N concentration and N/P were positively correlated with N addition, while the needle P was negatively correlated with nitrogen addition. With increase in nitrogen addition, Larix gmelinii increased its investment in its belowground parts, which may explain why Larix gmelinii tended to put more C in long-lived roots to improve its C utilization efficiency. Given the P deficiency caused by N addition, Larix gmelinii may be more likely to absorb P from the soil and adjust its C distribution to meet its P demand rather than relying on internal nutrient resorption.

In 2020, the coronavirus disease (COVID-19) broke out and swept rapidly all over the world. The Chinese and western integrative medicine, a unique medical model in China, has played an important role in the fight against the epidemic. We need to draw experience from the fight against the epidemic to promote the development of Chinese and western integrative medicine and provide intellectual support and theoretical guarantee for the national health and medical undertakings. First, we review the achievements of the Chinese and western integrative medicine since 1949 using literature review and questionnaire survey, and summarize the key roles of this integrative medicine in the prevention and control of COVID-19. Subsequently, we analyze the weaknesses of the integrative medicine in terms of medical resources, clinical education and research, and internationalization, and propose the construction goals for this discipline under the new circumstances in China, including the inheritance and innovation of the Chinese and western integrative medicine and a world-leading role in the integration of Chinese traditional medicine with western medicine. Furthermore, we suggest that China should improve the governance system for the Chinese and western integrative medicine, enhance talent training in this discipline, actively promote international exchange, and encourage the Chinese and western medicine integration culture.

[Image: see text] Allosteric HIV-1 integrase inhibitors (ALLINIs) have been of interest recently because of their novel mechanism of action. Strategic modifications to the C5 moiety of a class of 4-(4,4-dimethylpiperidinyl)-2,6-dimethylpyridinyl ALLINIs led to the identification of a tetrahydroisoquinoline heterocycle as a suitable spacer element to project the distal hydrophobic aryl ring. Subsequent optimization of the aryl substitutions identified 12 as an ALLINI with single-digit nanomolar inhibitory potency and low clearance across preclinical species. In preclinical toxicology studies with 12 in rats, lipid hepatocellular vacuolation was observed. Removal of the C6 methyl group resulted in GSK3839919 (22), which exhibited a reduced incidence and severity of lipid vacuolation in both in vitro assays and in vivo studies while maintaining the potency and pharmacokinetic (PK) properties of the prototype. The virology, PK, and toxicology profiles of 22 are discussed.

During the passing decade, taxi floating car data (FCD) has become an important tool to investigate urban trip choice behaviors and activities. The corresponding taxi exhaust reduction issue is also with rather significance for traffic emission mitigation in urban areas. By taking Shanghai as an empirical case, this paper analyzed the spatiotemporal characteristics of multimode travelers by combining the taxi FCD (from Qiangsheng Inc.), the metro smartcard data and the GPS trajectories of Mobike, one of the most popular shared bicycles in China, 2018). Binomial logit models (BNL) were proposed to estimate mode choices for both peak and off-peak periods by incorporating socio-economic, demographic, urban morphology, land use properties, and various trip-related variables. The choices between metro and taxi, Mobike and taxi were analyzed, respectively, with the corresponding influential factors identified. The results indicated that the percentage of residential and commercial land uses, the number of educational facilities have significant impacts on travel mode choice during peak hours, while the percentage of commercial land, the number of hospitals and bus lines are more prominent during off-peak periods. To quantify the emission reduction benefits, localized calculation of automobile exhaust was established according to the Vehicle Specific Power (VSP) based measurements obtained from the Portable Emission Measurement System (PEMS) experiments. Then, five corresponding emission mitigation schemes were proposed based on the model findings, and the cost-benefit of each countermeasure was further analyzed. Comparing with releasing the peak-hour crowdedness of metro stations, increasing Mobike supply, updating taxis into electric vehicles, and equipping taxis with catalytic converters, the scheme of removing non-motor vehicle restrictions was found with the shortest payback period and was consequently recommended as accordance with the proposal of urban eco and non-motorized transportation. Findings of this study is useful for transportation management in improving the mode share of metro and bicycles, thus to alleviate the congestion and auto emissions in urban areas.

In this paper, an approach to n-stage (n= 3, 4, 5...) balanced-to-single-ended out-of-phase power divider is proposed, which enhances the bandwidths for port matching, isolation and common-mode suppression firstly. Compared with the traditional single-ended multistage power divider, this approach has special circuits (common-mode and isolation circuits) for improving common-mode suppression and isolation, respectively. For common-mode suppression, the 180° microstrip line between the balanced port and the common-mode circuit composed by one parallel open stub are adopted to achieve wideband common-mode suppression. For isolation, the isolation circuits formed by cascade stage structure and parallel resistors are both adopted to improve the isolation bandwidth. The basic analysis at the center frequency is given, and for verifying the theoretical prediction, two prototypes of the 3-and 4-stage power dividers are fabricated and measured, which show 46.7% and 63% 20-dB operating bandwidths, and 0.25 dB and 0.3 dB minimum insertion loss, respectively. These two prototypes present that the 20-dB operating bandwidths are 16.7% and 33% wider than the single-stage balanced-to-single-ended power divider.

Designing organic charge-transfer (CT) cocrystals for efficient solar-thermal conversion is a long-sought goal but remains challenging. Here we construct a unique CT cocrystal by using a persistent 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS

Electrochromic materials have attracted much attention due to their promising applications in smart windows and thermal control. However, NiO is a weak point for a complementary ECD and needs to be improved due to its low optical modulation and charge density. In this work, the W-doped NiO films are designed and prepared by RF magnetron co-sputtering to improve the performance of the NiO. The results shows that the optical modulation of the W-NiO (52.7%) is significantly improved compared with pure NiO (33.8%), which can be assigned to the increase in lattice boundaries due to the W doping. The response time of W-NiO is 8.8 s for coloring and 7.2 s for bleaching, which is similar to that of NiO film. The all-solid-state electrochromic devices (ECDs) that employed W-NiO as a complementary layer are prepared and exhibit a high-transmittance modulation of 48.5% in wavelengths of 450–850 nm and an emittance modulation of 0.28 in 2.5–25 μm, showing great application potential in the field of smart windows and spacecraft thermal control devices. The strategy of preparing NiO doped by W indicates an innovative direction to obtain ECDs with high performance.

Objective. It is not clear which Traditional Chinese Medicine- (TCM-) related elements affect primary IgA nephropathy (IgAN) progression. Here, we explored the risk factors, based on TCM syndrome elements, related to the prognosis of primary IgAN patients. Methods. We analyzed patients with newly diagnosed, biopsy-proven IgAN at a single institution from December 2013 to September 2021. Basic clinical and pathological characteristics were assessed at the time of renal biopsy. The study endpoint was end-stage renal disease (ESRD: eGFR 30% from baseline. Kaplan‒Meier survival analysis was used to explore the role of TCM syndrome elements in IgAN progression. Multivariate Cox regression analysis with adjustment for traditional risk factors was performed to explore TCM syndrome elements that may influence patient prognosis. The factors correlated with TCM syndrome elements in IgAN patients were further evaluated by logistic regression analysis. Results. During a median follow-up of 22.0 months, 53 (12.5%) of the 423 included IgAN patients reached the study endpoint. The main IgAN disease location elements were the kidney, liver, and spleen. The main IgAN disease nature elements were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Kaplan‒Meier analysis identified three disease locations (liver, spleen, and kidney) and four disease natures (Qi-deficiency, Yang-deficiency, phlegm, and dampness) as elements associated with poor renal survival in IgAN patients. In multivariate Cox regression analysis, baseline Yang-deficiency was an independent risk predictor of poor prognosis in primary IgAN patients (hazard ratio 2.338; 95% confidence interval [CI]: 1.208–4.525; P = 0.012 ) after adjustment for traditional risk factors. Furthermore, logistic regression analysis identified being female (odds ratio [OR] 2.518; 95% CI: 1.538–4.122; P < 0.001 ), older age (OR 1.043; 95% CI: 1.022–1.065; P < 0.001 ), low hemoglobin levels (OR 0.984; 95% CI: 0.971–0.996; P = 0.013 ), and cellular/fibrocellular crescents (OR 1.706; 95% CI: 1.068–2.728; P = 0.026 ) as factors affecting Yang-deficiency in IgAN patients. Conclusions. Yang-deficiency independently predicts the risk of poor prognosis in primary IgAN patients. Being female, older age, low hemoglobin levels, and cellular/fibrocellular crescents were independently associated with Yang-deficiency in IgAN patients.

Increasing antibiotic resistance becomes a serious threat to public health. Photothermal therapy (PTT) and antibacterial enzyme-based therapy are promising nonresistant strategies for efficiently killing drug-resistant bacteria. However, the poor thermostability of enzymes in PTT hinders their synergistic therapy. Herein, antibacterial glucose oxidase (GOx) is embedded in a Ag graphitic nanocapsule (Ag@G) arrayed silk film to fabricate a GOx-synergistic PTT system (named silk-GOx-Ag@G, SGA). The SGA system can stabilize GOx by a vitrification process through the restriction of hydrogen bond and rigid β-sheet, and keep the antibacterial activity in the hyperthermal PTT environment. Moreover, the arrayed Ag@G possesses excellent chemical stability due to the protection of graphitic shell, providing stable plasmonic effect for integrating PTT and surface enhanced Raman scattering (SERS) analysis even in the GOx-produced H

An integrated trapped device (ITD) capable of removal of circulating tumor cells (CTCs) can assuage or even prevent metastasis. However, adhesion repertoires are ordinarily neglected in the design of ITDs, possibly leading to the omission of highly metastatic CTC and treatment failure. Here a vascular-like ITD with adhesive sites and wireless magnetothermal response to remove highly metastatic CTC in vivo is presented. Such a vascular-like ITD comprises circumferential well-aligned fibers and artificial adhesion repertoires and is optimized for magnetothermal integration. Continuous and repeated capture in a dynamic environment increases capture efficiency over time. Meanwhile, the heat generation of the ITD leads to the capture of CTC death owing to cell heat sensitivity. Furthermore, the constructed bioinspired ultrastructure of the ITD prevents vascular blockage and induces potential vascular regeneration. Overall, this work defines an extendable strategy for constructing adhesion repertoires against intravascular shear forces, provides a vascular-like ITD for reducing CTC counts, and is expected to alleviate the risk of cancer recurrence.

Herpes simplex virus (HSV) and cytomegalovirus (CMV) infections are commonly seen in immunocompromised patients, particularly in patients with HIV. However, fulminant CMV infection and concurrent infection with HSV and CMV in non-HIV patients are quite rare. We present the case of a 72-year-old HIV-negative man with a history of oropharyngeal carcinoma in remission and recent treatment of immune thrombocytopenic purpura with high-dose steroids who was transferred from an outside hospital for Ear Nose and Throat (ENT) evaluation of a non-healing buccal ulcer. During initial presentation, the patient was found to be febrile with acute hypoxic respiratory failure and a chest x-ray suggestive of bacterial pneumonia, though he failed to improve with broad-spectrum antibiotic therapy. He underwent esophagogastroduodenoscopy for dysphagia, which revealed a discrete ulcer positive for CMV. Biopsy of his buccal lesion was ultimately positive for HSV-1 and HSV-2. The patient's clinical status improved significantly following the initiation of antiviral therapy.It is important to consider CMV infection in the setting of persistent fever, respiratory distress, or dysphagia in the non-HIV infected patient, especially in the setting of prolonged steroid use. CMV and HSV infection can occur simultaneously at distinct sites in the body, and CMV infection may predispose to HSV reactivation due to its long term effect on cell-mediated immunity. Early recognition of opportunistic infections and initiation of antiviral therapy in immunocompromised patients can greatly affect length of hospital stay, morbidity, and, ultimately, mortality.

Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (&lt, 60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.

BACKGROUND: Mesangial proliferative glomerulonephritis (MsPGN) is an epidemic disease with increasing occurrence. As important as mesangial cells, podocytes are key innate cells for MsPGN prognosis and recovery. Renal progenitor cells, located at the urinary pole (UP) of Bowman’s capsule (BC), could alleviate kidney injury through their capacity to differentiate into podocytes. METHODS: Seventy-two male rats were categorized randomly into the sham (n=24), untreated Thy-1 (n=24) and losartan-treated (n=24) groups. We administered vehicle or losartan (50 mg/kg by gavage) daily to treat rats with anti-thy1.1 nephritis, an ideal model to simulate human MsPGN. Two weeks after the intravenous injection of antibody, urinary protein and blood samples were analyzed, pathological changes were examined, the number of podocytes was determined, and renal progenitor cells were studied. RESULTS: Anti-thy1.1 nephritis was significantly alleviated after losartan treatment, as reported previously and as expected. Compared with the untreated Thy-1 group, the number of podocytes in the losartan group increased, and the area of renal progenitor cells significantly increased. The protein expression of components of the p-ERK pathway was determined during the development of renal progenitor cells differentiating into podocytes. CONCLUSIONS: The data in this paper show the direct glomerular cell action of angiotensin II receptor blocker (ARB) treatment in improving outcomes in anti-thy1.1 nephritis. The positive effects of ARB medication on anti-thy1.1 nephritis were due to an increase in the number of renal epithelial progenitor cells (defined as PECs that expressed only stem cell markers without podocyte proteins).

The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in the elderly. To examine this question, bilateral renal IRI was induced in old (24 months) mice three weeks after parabiosis model establishment. At 24 hours after IRI, compared to old wild-type mice, the old mice with IRI had significantly damaged renal histology, decreased renal function, increased oxidative stress, inflammation, and apoptosis. However, there was no increase in autophagy. Compared to old mice with IRI, old-old parabiosis mice with IRI did not show differences in renal histological damage, oxidative stress, inflammation, apoptosis, or autophagy, but did exhibit improved renal function. Compared to the old-old parabiosis mice with IRI, the old mice with IRI in the young (12 week)-old parabiosis showed less renal histological injury and better renal function. Renal oxidative stress, inflammation, and apoptosis were significantly decreased, and autophagy was significantly increased. Thus, a youthful systemic milieu may decrease oxidative stress, inflammation, and apoptosis, and increase autophagy in old mice with IRI. These effects ameliorated IRI injuries in old mice. Our study provides new ideas for effectively preventing and treating AKI in the elderly.

Human respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide and repeatedly infects immunocompetent individuals throughout life. Severe lower airway RSV infection during infancy can be life-threatening, but is also associated with important sequelae including development of asthma and recurrent wheezing in later childhood. The basis for the inadequate, short-lived adaptive immune response to RSV infection is poorly understood, but it is widely recognized that RSV actively antagonizes Type I interferon (IFN) production. In addition to the induction of the anti-viral state, IFN production during viral infection is critical for downstream development of robust, long-lived immunity. Based on the hypothesis that a vaccine that induced robust IFN production would be protective, we previously constructed a Newcastle disease virus-vectored vaccine that expresses the F glycoprotein of RSV (NDV-F) and demonstrated that vaccinated mice had reduced lung viral loads and an enhanced IFN-γ response after RSV challenge. Here we show that vaccination also protected cotton rats from RSV challenge and induced long-lived neutralizing antibody production, even in RSV immune animals. Finally, pulmonary eosinophilia induced by RSV infection of unvaccinated cotton rats was prevented by vaccination. Overall, these data demonstrate enhanced protective immunity to RSV F when this protein is presented in the context of an abortive NDV infection.

Iterative structure–activity analyses in a class of highly functionalized furo[2,3-b]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (14) is described.

A new divergent ligand (3a) containing a triaryl core and two imidazole side-arms has been designed and synthesized. The synthetic procedure utilizes a two-step strategy, i.e. the Krohnke condensation, followed by a Cu-catalyzed Ullman-type coupling. This synthetic strategy allows the facile introduction of various substituents on the 4-position of the central pyridine in the ligands, which was proved by the synthesis of a ligand analog (3b). The new ligands were well characterized by spectroscopic methods and X-ray structural analysis was carried out for 3a. Reaction of 3a with Co(NCS)2 by a layering method afforded single crystals of a coordination polymer 5, which was structurally characterized by X-ray diffraction. 5 is composed of two ligands and one Co(NCS)2 in its asymmetric unit and features a 1-D coordination polymer with nano-scale metallomacrocyles. The structure of 5 is found to be quite different from all known coordination networks composed of Co(NCS)2 and closely related divergent ligands.

For the rapid measurement of an analyte in complex samples using near-infrared (NIR) spectroscopy, appropriate wavelength selection is an important and albeit difficult aspect, which is essential for improving prediction performance. Based on equidistant combination partial least squares (EC-PLS), an equivalence model set was proposed. A wavelength selection method, called repetition rate priority combination PLS (RRPC-PLS), was further proposed and applied for NIR analysis of human serum albumin. The competitive adaptive reweighted sampling combined PLS (CARS-PLS) and EC-PLS, which are well-performed wavelength selection methods, were also conducted for comparison. Based on the various divisions of calibration and prediction sets, the modeling was performed to achieve parameter stability. The posterior sample group excluded in modeling was used to validate and achieve an objective evaluation. Using CARS-PLS, EC-PLS and RRPC-PLS methods, the selected optimal models included 32, 36 and 24 wavelengths, respectively. A simpler and high performance model with 15 wavelengths was also selected with RRPC-PLS method. The root-mean-square errors and correlation coefficients for validation were 0.505 g L −1 and 0.997 for the optimal RRPC-PLS model and 0.530 g L −1 and 0.997 for the RRPC-PLS model ( N =15), respectively. The validation effects were superior to the previous two methods in two aspects of prediction performance and model complexity. The prediction values were close to the measured values with high precision. The results showed that RRPC-PLS is the good improvement on EC-PLS, which can be more effective to enhance the prediction performance and remove the redundant wavelengths.

Objective. This study investigated the association between body constitution (BC) and the prognosis of IgA nephropathy. Methods. We analyzed 203 biopsy-diagnosed IgA nephropathy patients, who were followed up for (63.9±16.2) months. The participants’ BC statuses were evaluated with the Constitution in Chinese Medicine Questionnaire; the relationships between clinical parameters and renal outcomes were analyzed by Cox regression. Results. Patients were classified into chronic kidney disease stages with 43.4% in stage 1, 27.1% in stage 2, 26.1% in stage 3, 3.5% in stage 4, and none in stage 5. Qi-deficiency BC type was the most common BC type in IgA nephropathy patients. In univariate analysis, proteinuria of more than 1g/d, hypertension, renal impairment (estimated glomerular filtration rate P=0.009), renal impairment (HR 5.8, P P=0.041), and blood-stasis BC (HR 2.5, P=0.017) were independent predictors of unfavorable renal outcomes. Conclusions. Most patients of IgA nephropathy were biopsied at an early stage. Yang-deficiency BC and blood-stasis BC at biopsy were most closely associated with the worse prognosis of IgA nephropathy along with hypertension and renal impairment.

Although a range of nanoparticles have been developed as drug delivery systems in cancer therapeutics, this approach faces several important challenges concerning nanocarrier circulation, clearance, and penetration. The impact of reducing nanoparticle size on penetration through leaky blood vessels around tumor microenvironments via enhanced permeability and retention (EPR) effect has been extensively examined. Recent research has also investigated the effect of nanoparticle shape on circulation and target binding affinity. However, how nanoparticle shape affects drug release and therapeutic efficacy has not been previously explored. Here, we compared the drug release and efficacy of iron oxide nanoparticles possessing either a cage shape (IO-NCage) or a solid spherical shape (IO-NSP). Riluzole cytotoxicity against metastatic cancer cells was enhanced three-fold with IO-NCage. The shape of nanoparticles (or nanocages) affected the drug release point and cellular internalization, which in turn influenced drug efficacy. Our study provides evidence that the shape of iron oxide nanoparticles has a significant impact on drug release and efficacy.

The replacement of precious metals with inexpensive, less toxic, and earth-abundant elements in typical noble-metal-mediated organic transformations is a major goal in current synthetic chemistry and industries. The metal-catalyzed N-alkylation of amines with other amines through a “hydrogen-borrowing” principle represents a green and atom-economical reaction for the synthesis of secondary amines. However, catalysts developed thus far that are effective for this process remain quite scarce and are only limited to a few ruthenium and iridium complexes. In this work, we present a cobalt-catalyzed selective alkylation of amines with amines to synthesize a large variety of secondary amines. A range of amine substrates have been converted to the corresponding products through hetero- or homocoupling between amines. Cyclic sec-amines are also achieved from diamine precursors as rare examples.

6,6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3,4-d]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein.

As an important component of urban roads, signalized intersections have contributed significantly to motor vehicle emissions, which however has not been modelled in high accuracy. This paper uses the International Vehicle Emission (IVE) model to obtain the localized emission factors, so that a dispersion model, CAL3QHC was introduced and modified to incorporate the vehicle acceleration and deceleration states. Two emission reduction schemes for urban signalized intersections, the Green Light Optimal Speed Advisory (GLOSA) system and the no-obstacle driveway design, were proposed, by taking the intersection of Wen'er West Road and Liangmu Road in Hangzhou, China as an empirical example. The overall performance and roadside emission dispersion were simulated using VISSIM software package, with the improved CAL3QHC model. The GLOSA system and the no-obstacle driveway design were found to mitigate the roadside CO concentration by 21.2% and 22.1%, respectively. Findings of the study may assist to monitor roadside pollutant concentrations, formulate and evaluate emission mitigation strategies in urban intersections.