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In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

The Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum, and the effect of the antioxidation reaction on cell plasticity, remain unknown. N-acetyl-L-cysteine (NAC) induced the early commitment of the differentiation of granule cell precursors (GCPs) to neurons, especially Purkinje cells, via the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis; moreover, Jdp2 depletion enhanced this differentiation program of GCPs. The antioxidative effect of NAC was the main driving force of this decision toward the neural differentiation of the GCP population in the presence of Gabra6 in vitro. This implies that antioxidative drugs are effective agents for rescuing oxidative-stress-induced GCP damages in the cerebellum and commit this Gabra6-positive cell population toward differentiation into Purkinje cells., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The animal welfare guidelines published by the Animal Care Committee of the RIKEN BioResource Research Center (BRC) in Japan (Kiteisv.intra.riken.jp/JoureiV5HTMLContents/act/print/print110000514.htm), the National Laboratory Animal Center (NLAC)(106022), and the Kaohsiung Medical University in Taiwan (106189; 107128; 108244) were used for the care of laboratory animals [10, 11]. Various organs were isolated from the Jdp2-KO mice (RIKEN Modified SHIRPA; https://ja.brc.riken.jp/lab/jmc/shirpa/en/ ) and evaluated for LacZ expression. The strategy used to produce the Jdp2-KO mouse has been described elsewhere [42, 43]. Primary GCPs were prepared as described previously [10, 11]., (© 2024. The Author(s).)

Objective: The aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels., Methods: A cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy., Results: Among the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01)., Conclusion: In cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI., (© 2024. The Author(s).)

Cellular mechanical force plays a crucial role in numerous biological processes, including wound healing, cell development, and metastasis. To enable imaging of intercellular tension, molecular tension probes were designed, which offer a simple and efficient method for preparing Au-DNA intercellular tension probes with universal applicability. The proposed approach utilizes gold nanoparticles linked to DNA hairpins, enabling sensitive visualization of cellular force in vitro . Specifically, the designed Au-DNA intercellular tension probe includes a molecular spring flanked by a fluorophore-quencher pair, which is anchored between cells. As intercellular forces open the hairpin, the fluorophore is de-quenched, allowing for visualization of cellular force. The effectiveness of this approach was demonstrated by imaging the cellular force in living cells using the designed Au-DNA intercellular tension probe., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chiral amides are important structure in many natural products and pharmaceuticals, yet their efficient synthesis from simple amide feedstock remains challenge due to its weak Lewis basicity. Herein, we describe our study of the enantioselective synthesis of chiral amides by N-alkylation of primary amides taking advantage of an achiral rhodium and chiral squaramide co-catalyzed carbene N-H insertion reaction. This method features mild condition, rapid reaction rate (in all cases 1 min) and a wide substrate scope with high yield and excellent enantioselectivity. Further product transformations show the synthetic potential of this reaction. Mechanistic studies reveal that the non-covalent interactions between the catalyst and reaction intermediate play a critical role in enantiocontrol., (© 2024. The Author(s).)

Subcellular metabolomics analysis is crucial for understanding intracellular heterogeneity and accurate drug-cell interactions. Unfortunately, the ultra-small size and complex microenvironment inside the cell pose a great challenge to achieving this goal. To address this challenge, we propose an artificial intelligence-assisted subcellular mass spectrometry imaging (AI-SMSI) strategy with in situ image segmentation. Based on the nanometer-resolution MSI technique, the protonated guanine and threonine ions were respectively employed as the nucleus and cytoplasmic markers to complete image segmentation at the subcellular level, avoiding mutual interference of signals from various compartments in the cell. With advanced AI models, the metabolites within the different regions could be further integrated and profiled. Through this method, we decrypted the distinct action mechanism of isomeric drugs, doxorubicin (DOX) and epirubicin (EPI), only with a stereochemical inversion at C-4'. Within the cytoplasmic region, fifteen specific metabolites were discovered as biomarkers for distinguishing the drug action difference between DOX and EPI. Moreover, we identified that the downregulations of glutamate and aspartate in the malate-aspartate shuttle pathway may contribute to the higher paratoxicity of DOX. Our current AI-SMSI approach has promising applications for subcellular metabolomics analysis and thus opens new opportunities to further explore drug-cell specific interactions for the long-term pursuit of precision medicine., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M ( Q 1 , Q 3 ) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] ( P <0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) ( t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.

Gastric cancer (GC) organoids are frequently used to examine cell proliferation and death as well as cancer development. Invasion/migration assay, xenotransplantation, and reactive oxygen species (ROS) production were used to examine the effects of antioxidant drugs, including perillaldehyde (PEA), cinnamaldehyde (CA), and sulforaphane (SFN), on GC. PEA and CA repressed the proliferation of human GC organoids, whereas SFN enhanced it. Caspase 3 activities were also repressed on treatment with PEA and CA. Furthermore, the tumor formation and invasive activities were repressed on treatment with PEA and CA, whereas they were enhanced on treatment with SFN. These results in three-dimensional (3D)-GC organoids showed the different cancer development of phase II enzyme ligands in 2D-GC cells. ROS production and the expression of TP53, nuclear factor erythroid 2-related factor (NRF2), and Jun dimerization protein 2 were also downregulated on treatment with PEA and CA, but not SFN. NRF2 knockdown reversed the effects of these antioxidant drugs on the invasive activities of the 3D-GC organoids. Moreover, ROS production was also inhibited by treatment with PEA and CA, but not SFN. Thus, NRF2 plays a key role in the differential effects of these antioxidant drugs on cancer progression in 3D-GC organoids. PEA and CA can potentially be new antitumorigenic therapeutics for GC.

The enantioselective addition of potent nucleophiles to ketenes poses challenges due to competing background reactions and poor stereocontrol. Herein, we present a method for enantioselective phosphoric acid catalyzed amination of ketenes generated from α-aryl-α-diazoketones. Upon exposure to visible light, the diazoketones undergo Wolff rearrangement to generate ketenes. The phosphoric acid not only accelerates ketene capture by amines to form a single configuration of aminoenol intermediates but also promotes an enantioselective proton-transfer reaction of the intermediates to yield the products. Mechanistic studies elucidated the reaction pathway and explained how the catalyst expedited the transformation and controlled the enantioselectivity., (© 2023 Wiley-VCH GmbH.)

Core-shell photoanodes have shown great potential for photoelectrochemical (PEC) water oxidation. However, the construction of a high-quality interface between the core and shell, as well as a highly catalytic surface, remains a challenge. Herein, guided by computation, we present a BiVO 4 photoanode coated with ZnCoFe polyphthalocyanine using pyrazine as a coordination agent. The bidirectional axial coordination of pyrazine plays a dual role by facilitating intimate interfacial contact between BiVO 4 and ZnCoFe polyphthalocyanine, as well as regulating the electron density and spin configuration of metal sites in ZnCoFe phthalocyanine, thereby promoting the potential-limiting step of *OOH desorption. The resulting photoanode displayed a high photocurrent density of 5.7±0.1 mA cm -2 at 1.23 V RHE . This study introduces a new approach for constructing core-shell photoanodes, and uncovers the key role of pyrazine axial coordination in modulating the catalytic activity of metal phthalocyanine., (© 2023 Wiley-VCH GmbH.)

Background: Crosstalk between the aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is called the "AhR-Nrf2 gene battery", which works synergistically in detoxification to support cell survival. Nrf2-dependent phase II gene promoters are controlled by coordinated recruitment of the AhR to adjacent dioxin responsive element (DRE) and Nrf2 recruitment to the antioxidative response element (ARE). The molecular interaction between AhR and Nrf2 members, and the regulation of each target, including phase I and II gene complexes, and their mediators are poorly understood., Methods: Knockdown and forced expression of AhR-Nrf2 battery members were used to examine the molecular interactions between the AhR-Nrf2 axis and AhR promoter activation. Sequential immunoprecipitation, chromatin immunoprecipitation, and histology were used to identify each protein complex recruited to their respective cis-elements in the AhR promoter. Actin fiber distribution, cell spreading, and invasion were examined to identify functional differences in the AhR-Jdp2 axis between wild-type and Jdp2 knockout cells. The possible tumorigenic role of Jdp2 in the AhR-Nrf2 axis was examined in mutant Kras-Trp53-driven pancreatic tumors., Results: Crosstalk between AhR and Nrf2 was evident at the transcriptional level. The AhR promoter was activated by phase I ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the AhR-Jdp2-Nrf2 axis in a time- and spatial transcription-dependent manner. Jdp2 was a bifunctional activator of DRE- and ARE-mediated transcription in response to TCDD. After TCDD exposure, Jdp2 activated the AhR promoter at the DRE and then moved to the ARE where it activated the promoter to increase reactive oxygen species (ROS)-mediated functions such as cell spreading and invasion in normal cells, and cancer regression in mutant Kras-Trp53-driven pancreatic tumor cells., Conclusions: Jdp2 plays a critical role in AhR promoter activation through the AhR-Jdp2-Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras-Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression., (© 2023. Japanese Society of Inflammation and Regeneration.)

The World Health Organization has reported radioactive Rn gas as the second leading cause of lung cancer and gives an extreme limit to indoor Radon (Rn) concentration as 100 Bq/m 3 . To realize rapid and accurate Rn monitoring, we report an efficient visualized electrochemiluminescence (ECL) device for Rn detection with the lowest limit of detection (0.9 Bq/m 3 /3.6 Bq h m -3 ) compared to known Rn detection methods and the shortest measurement time (less than 5 h) among non-pump methods. In detail, an efficient Rn probe is prepared by Au nanoparticles, Pb 2+ aptamer, as well as NH 2 -ssDNA co-reactant and then modified on ITO electrodes to obtain Rn detection devices. With tris(2,2'-bipyridyl)ruthenium(II)chloride (Ru(bpy) 3 Cl 2 ) as an ECL emitter, the devices can exhibit ultra-high sensitivity and selectivity to trace Rn in environment via the ECL quenching caused by 210 Pb, the relatively stable decay product of Rn. Furthermore, ECL imaging technology can be applied to realize the visualized Rn detection. An efficient up-response ECL detector was also invented to support this detection device to achieve accurate Rn detection in environment. This work reports noble gas ECL detection for the first time and provides an efficient strategy for rapid and accurate monitoring of trace Rn in environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pK a Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pK a Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol., (© 2023 Wiley-VCH GmbH.)

We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori ( H. pylori ). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of H. pylori -infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori -infected cancer organoid. To clarify the role of HDGF and TNFα secreted from H. pylori -infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori , but TNFα decreased the cell viability in H. pylori -infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori -infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by H. pylori . Recombinant HDGF and TNFα inhibited the development and invasion of H. pylori -infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of H. pylori -infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.

Obesity is a severe disease worldwide. Mitochondrial autophagy (mitophagy) may be related to metabolic abnormalities in obese individuals, but the mechanism is still unclear. We aimed to investigate whether nuclear receptors NR1D1 and ULK1 influence obesity by affecting mitophagy. In vitro model was established by inducing 3T3-L1 cells differentiation. MTT was detected cell viability. ELISA was tested triglyceride (TG). Oil red O staining was performed to detect lipid droplets. Flow cytometry was measured mtROS. ChIP and Dual-luciferase reporter assay were verified NR1D1 bind to ULK1. LC3 level was detected by IF. After differentiation medium treatment, cell viability was decreased, TG content and lipid droplets were increased Moreover, NR1D1 expression was reduced in Model group. NR1D1 overexpression was increased cell viability, reduced TG content and lipid droplets. Subsequently, NR1D1 inhibited TOM20 and mtROS, whereas, Parkin and PINK1 were accelerated. NR1D1 overexpression facilitated LC3 expression, whereas ULK1 knockdown was reversed the effect of NR1D1 overexpression. Liensinine also reversed the effect of NR1D1 overexpression, that is, cell viability was reduced, mtROS, TG content and lipid droplets were increased. The combination of nuclear receptor NR1D1 and ULK1 promoted mitophagy in adipocytes to alleviate obesity, which provided new target and strategy for obesity treatment. Abbreviations : Mitochondrial autophagy (mitophagy), triglyceride (TG), Uncoordinated-51 like autophagy activating kinase 1 (ULK1), Nuclear receptor subfamily 1 group D member 1 (NR1D1), American Type Culture Collection (ATCC), fetal bovine serum (FBS), 3-isobutyl-1-methylxanthine (IBMX), dexamethasone (DEX), short hairpin RNA ULK1 (sh-ULK1), wild-type (WT), mutant (MUT), Enzyme-linked immunosorbent assay (ELISA), mitochondrial reactive oxygen species (mtROS), Chromatin immunoprecipitation (ChIP), Quantitative real-time PCR (qRT-PCR), Immunofluorescence (IF), standard deviation (SD).

Stomach cancer has a high mortality, which is partially caused by an absence of suitable biomarkers to allow detection of the initiation stages of cancer progression. Thus, identification of critical biomarkers associated with gastric cancer (GC) is required to advance its clinical diagnoses and treatment. Recent studies using tracing models for lineage analysis of GC stem cells indicate that the cell fate decision of the gastric stem cells might be an important issue for stem cell plasticity. They include leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5 + ), Cholecystokinin receptor 2 (Cckr2 + ), and axis inhibition protein 2 (Axin2 + ) as the stem cell markers in the antrum, Trefoil Factor 2 (TFF2 + ), Mist1 + stem cells, and Troy+ chief cells in the corpus. By contrast, Estrogen receptor 1 (eR1), Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), SRY (sex determining region Y)-box 2 (Sox2), and B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) are rich in both the antrum and corpus regions. These markers might help to identify the cell-lineage identity and analyze the plasticity of each stem cell population. Thus, identification of marker genes for the development of GC and its environment is critical for the clinical application of cancer stem cells in the prevention of stomach cancers.

Objective: This study aims to investigate the expressions of matrix metalloproteinase-9 (MMP-9), estrogen receptor (ER), and progesterone receptor (PR) in thin endometrium., Methods: Patients who received treatment in our hospital between January 2018 and September 2020 were enrolled. Endometrial thickness was measured using transvaginal ultrasound; in patients with a midluteal phase endometrial thickness of <7 mm, a sample of endometrial tissue was obtained using a hysteroscope, and the MMP-9, ER, and PR expressions were detected using immunohistochemistry. In addition, the number of endometrial glands was calculated in a complete field of view under a low-power (100×) microscope, and the serum estrogen and progesterone levels were determined. Following hormone therapy, the midluteal phase endometrial thickness was measured again using transvaginal ultrasound, and the patients were divided into two groups: the thin endometrium group and the normal endometrium group ( n  = 50, each). Patients in the thin endometrium group had an endometrial thickness of <7 mm, while patients in the normal endometrium group had an endometrial thickness of 7-10 mm., Results: The number of endometrial glands as well as the ER and MMP-9 expressions were lower in the thin endometrium group than in the normal endometrium group; the differences were statistically significant ( p  < .05). The receiver operator characteristic curve revealed that ER and MMP-9 had a high prediction accuracy in patients with refractory thin endometrium, while the number of endometrial glands was moderately predictive., Conclusion: Compared with other patients with thin endometrium, patients with refractory thin endometrium had a reduced the number of endometrial glands and significantly lower ER and MMP-9 expressions.

The photoelectrocatalytic (PEC) oxidation of glycerol into highly value-added products is attractive, but it is extremely challenging to limit the oxidation products to the valuable C3 chemicals. The hole concentration and surface atomic arrangement of a photoanode can be modulated by controlling facet exposure, thus tuning the activity and selectivity. Herein, we report for the first time the formation of a WO 3 photoanode with predominant exposure of {202} facets by a secondary hydrothermal method. The photoanode exhibits superior PEC glycerol conversion efficiency, giving an 80% selectivity to glyceraldehyde with a production rate of 462 mmol h -1 m -2 . Also, the faraday efficiency for the C3 product reaches 98.6%. We made comparison between the {202} facets and the commonly studied {200} facets using experimental and theoretical methods. It is disclosed that the former enhances not only the adsorption and activation of glycerol via the terminal hydroxyl groups but also the desorption of glyceraldehyde.

The use of biomarkers in cancer diagnosis, therapy, and prognosis has been highly effective over several decades. Studies of biomarkers in cancer patients pre- and post-treatment and during cancer progression have helped identify cancer stem cells (CSCs) and their related microenvironments. These analyses are critical for the therapeutic application of drugs and the efficient targeting and prevention of cancer progression, as well as the investigation of the mechanism of the cancer development. Biomarkers that characterize CSCs have thus been identified and correlated to diagnosis, therapy, and prognosis. However, CSCs demonstrate elevated levels of plasticity, which alters their functional phenotype and appearance by interacting with their microenvironments, in response to chemotherapy and radiotherapeutics. In turn, these changes induce different metabolic adaptations of CSCs. This article provides a review of the most frequently used CSCs and stem cell markers.

Infection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. We aimed to examine the association between the airway microbiota and infection and rejection in lung transplant recipients (LTRs). Here, we collected 181 sputum samples (event-free, n  = 47; infection, n  = 103; rejection, n  = 31) from 59 LTRs, and performed 16S rRNA gene sequencing to analyze the airway microbiota. A significantly different airway microbiota was observed among event-free, infection and rejection recipients, including microbial diversity and community composition. Nineteen differential taxa were identified by linear discriminant analysis (LDA) effect size (LEfSe), with 6 bacterial genera, Actinomyces, Rothia, Abiotrophia, Neisseria, Prevotella , and Leptotrichia enriched in LTRs with rejection. Random forest analyses indicated that the combination of the 6 genera and procalcitonin (PCT) and T-lymphocyte levels showed area under the curve (AUC) values of 0.898, 0.919 and 0.895 to differentiate between event-free and infection recipients, event-free and rejection recipients, and infection and rejection recipients, respectively. In conclusion, our study compared the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota can be a potential indicator to differentiate between infection and acute rejection after LT. IMPORTANCE Survival after LT is limited compared with other solid organ transplantations mainly due to infection- and rejection-related complications. Differentiating infection from rejection is one of the most important challenges to face after LT. Recently, the airway microbiota has been reported to be associated with either infection or rejection of LTRs. However, fewer studies have investigated the relationship between airway microbiota together with infection and rejection of LTRs. Here, we conducted an airway microbial study of LTRs and analyzed the airway microbiota together with infection, acute rejection, and clinically stable recipients. We found different airway microbiota between infection and acute rejection and identify several genera associated with each outcome and constructed a model that incorporates airway microbiota and clinical parameters to predict outcome. This study highlighted that the airway microbiota was a potential indicator to differentiate between infection and acute rejection after LT.

The aryl hydrocarbon receptor (AhR) is a ligand-binding protein that responds to environmental aromatic hydrocarbons and stimulates the transcription of downstream phase I enzyme-related genes by binding the cis element of dioxin-responsive elements (DREs)/xenobiotic-responsive elements. Dimethyl sulfoxide (DMSO) is a well-known organic solvent that is often used to dissolve phase I reagents in toxicology and oxidative stress research experiments. In the current study, we discovered that 0.1% DMSO significantly induced the activation of the AhR promoter via DREs and produced reactive oxygen species, which induced apoptosis in mouse embryonic fibroblasts (MEFs). Moreover, Jun dimerization protein 2 (Jdp2) was found to be required for activation of the AhR promoter in response to DMSO. Coimmunoprecipitation and chromatin immunoprecipitation studies demonstrated that the phase I-dependent transcription factors, AhR and the AhR nuclear translocator, and phase II-dependent transcription factors such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) integrated into DRE sites together with Jdp2 to form an activation complex to increase AhR promoter activity in response to DMSO in MEFs. Our findings provide evidence for the functional role of Jdp2 in controlling the AhR gene via Nrf2 and provide insights into how Jdp2 contributes to the regulation of ROS production and the cell spreading and apoptosis produced by the ligand DMSO in MEFs., (© 2021. The Author(s).)

Owing to the characteristics of high throughput, high flexibility, and convenient separation of the sensing and reporting reactions, the bipolar electrode (BPE) shows great potential in clinical analysis. However, there are some difficulties in the combination of BPEs and multiplex electrochemiluminescence (ECL) biosensing, such as the need for small sample consumption, multistep operations, and separated sample loading. In this paper, a microfluidic BPE array chip was fabricated toward multiplex detection of cancer biomarkers. With a special channel structure and the difference in flow resistance of channels of different sizes, the direction of liquid flow was successfully controlled. In this way, rapid and automatic multiplex sampling was achieved on the array, which would help improve the sensing efficiency and reduce the reagent consumption. The ECL BPE array chip served as an immunosensor for multiple prostate cancer biomarkers including prostate-specific antigen (PSA), interleukin-6 (IL-6), and prostate-specific membrane antigen (PSMA). The microfluidic BPE chip shows good reproducibility and high sensitivity. The limits of detection for PSA, IL-6, and PSMA are 0.093 ng/mL, 0.061 pg/mL, and 0.059 ng/mL, respectively. It also exhibits excellent performance in real sample analysis. The integrated ECL BPE array shows a good application prospect in clinical sensing of cancer biomarkers, as well as point-of-care testing.

A label-free and fast approach for positive electrochemiluminescence (ECL) imaging of single cells by bipolar nanoelectrode array is proposed. The reduction of oxygen at a platinized gold nanoelectrode array in a closed bipolar electrochemical system is coupled with an oxidative ECL process at the anodic side. For elevating the ECL imaging contrast of single cells, a driving voltage of -2.0 V is applied to in situ generate oxygen confined beneath cells that is subsequently used for ECL imaging at 1.1 V. High oxygen concentration in the confined space resulting from steric hindrance generates prominent oxygen reduction current at the cathodic side and higher ECL intensity at the anodic side, allowing positive ECL imaging of the cells adhesion region with excellent contrast. Cell morphology and adhesion strength can be successfully imaged with high image acquisition rate. This approach opens a new avenue for label-free imaging of single cells., (© 2021 Wiley-VCH GmbH.)

There is considerable cellular diversity in the human stomach, which has helped to clarify cell plasticity in normal development and tumorigenesis. Thus, the stomach is an interesting model for understanding cellular plasticity and for developing prospective anticancer therapeutic agents. However, many questions remain regarding the development of cancers in vivo and in vitro in two- or three-dimensional (2D/3D) cultures, as well as the role of Helicobacter pylori ( H. p. ) infection. Here, we focus on the characteristics of cancer stem cells and their derived 3D organoids in culture, including the formation of stem cell niches. We define the conditions required for such organoid culture in vitro and examine the ability of such models for testing the use of anticancer agents. We also summarize the signaling cascades and the specific markers of stomach-cancer-derived organoids induced by H. p. infection, and their stem cell niches.

The outbreak of coronavirus disease 2019 (COVID-19) has disproportionately affected patients with comorbidities, including recipients of solid organ and hematopoietic stem cell transplants (SCT). Upon recovery from COVID-19, the degree of the immunological protection from reinfection remains unclear. Here we describe a 33-year-old patient with erythropoietic protoporphyria (EPP) who had undergone liver transplantation with splenectomy followed by allogeneic SCT in 2013 after an initial failed liver and umbilical cord transplant. The patient developed mild upper respiratory symptoms in the spring of 2020 and was found to have anti-SARS-CoV2 antibodies suggesting past infection. A comprehensive analysis of T cell functionality in peripheral blood from this patient revealed robust in vitro responses against SARS CoV2 antigens Spike (S) 1 and 2, membrane (M) and nucleoprotein (NP), comparable to the reactivity against common antigens from CMV, EBV, Ad and BK viruses, while only low reactivity was seen in healthy donors without documented history of COVID-19. Moreover, the patient displayed a marked recognition of counterpart antigens from related human coronaviruses (hCoVs) 229E, OC43, NL63 and HKU1. Thus, despite lifelong immunosuppression, this survivor of COVID-19 retained a remarkable degree of immunocompetence and showed broad-spectrum T cell memory specific for SARS-CoV2 and related hCoVs including less studied hCoV M and NP antigens. The study highlights the role of cellular immunity after natural COVID-19 infection, suggesting broader use of T cell assays as a tool for risk stratification, measurement of immunocompetence and/or post-infection or post-vaccination protection, and possible T cell-based adoptive immunotherapy strategies in high-risk patients., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2021. Published by Elsevier Inc.)

The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore, new therapeutic strategies targeting tumor suppressor gene products may help prevent the progression of pancreatic cancer. In this review, we discuss several recent clinical trials of pancreatic cancer and recent studies reporting safe and effective treatment modalities for patients with advanced pancreatic cancer.

Background: The cerebellum is the sensitive region of the brain to developmental abnormalities related to the effects of oxidative stresses. Abnormal cerebellar lobe formation, found in Jun dimerization protein 2 (Jdp2)-knockout (KO) mice, is related to increased antioxidant formation and a reduction in apoptotic cell death in granule cell progenitors (GCPs). Here, we aim that Jdp2 plays a critical role of cerebellar development which is affected by the ROS regulation and redox control., Objective: Jdp2-promoter-Cre transgenic mouse displayed a positive signal in the cerebellum, especially within granule cells. Jdp2-KO mice exhibited impaired development of the cerebellum compared with wild-type (WT) mice. The antioxidation controlled gene, such as cystine-glutamate transporter Slc7a11, might be critical to regulate the redox homeostasis and the development of the cerebellum., Methods: We generated the Jdp2-promoter-Cre mice and Jdp2-KO mice to examine the levels of Slc7a11, ROS levels and the expressions of antioxidation related genes were examined in the mouse cerebellum using the immunohistochemistry., Results: The cerebellum of Jdp2-KO mice displayed expression of the cystine-glutamate transporter Slc7a11, within the internal granule layer at postnatal day 6; in contrast, the WT cerebellum mainly displayed Sla7a11 expression in the external granule layer. Moreover, development of the cerebellar lobes in Jdp2-KO mice was altered compared with WT mice. Expression of Slc7a11, Nrf2, and p21 Cip1 was higher in the cerebellum of Jdp2-KO mice than in WT mice., Conclusion: Jdp2 is a critical regulator of Slc7a11 transporter during the antioxidation response, which might control the growth, apoptosis, and differentiation of GCPs in the cerebellar lobes. These observations are consistent with our previous study in vitro.

Aggregation-induced emission (AIE) active Pdots are attractive nanomaterials applied in electrochemiluminescence (ECL) fields, while the irreversible redox reaction of these Pdots is a prevailing problem, resulting in instability of ECL emission. Herein, we first designed and synthesized an AIE-active Pdot with reversible redox property, which contains a tetraphenylethene derivate and benzothiadiazole (BT) to achieve stable ECL emission. BT has a good rigid structure with excellent electrochemical behaviors, which is beneficial for avoiding the destruction of the conjugated structure as much as possible during the preparation of Pdots, thus maintaining good redox property. The tetraphenylethene derivate, as a typical AIE-active moiety, provides a channel for highly efficient luminescence in the aggregated states. The Pdots exhibited reversible and quasi-reversible electrochemical behaviors during cathodic and anodic scanning, respectively. The stable annihilation, reductive-oxidative, and oxidative-reductive ECL signals were observed. Subsequently, we constructed an ultrasensitive ECL biosensor based on the oxidative-reductive ECL mode for the detection of miRNA-21 with a detection limit of 32 aM. This work provides some inspiration for the future design of ECL materials featuring AIE-active property and stable ECL emission.

The introduction of oxygen vacancies (Ov) has been regarded as an effective method to enhance the catalytic performance of photoanodes in oxygen evolution reaction (OER). However, their stability under highly oxidizing environment is questionable but was rarely studied. Herein, NiFe-metal-organic framework (NiFe-MOFs) was conformally coated on oxygen-vacancy-rich BiVO 4 (Ov-BiVO 4 ) as the protective layer and cocatalyst, forming a core-shell structure with caffeic acid as bridging agent. The as-synthesized Ov-BiVO 4 @NiFe-MOFs exhibits enhanced stability and a remarkable photocurrent density of 5.3±0.15 mA cm -2 at 1.23 V (vs. RHE). The reduced coordination number of Ni(Fe)-O and elevated valence state of Ni(Fe) in NiFe-MOFs layer greatly bolster OER, and the shifting of oxygen evolution sites from Ov-BiVO 4 to NiFe-MOFs promotes Ov stabilization. Ovs can be effectively preserved by the coating of a thin NiFe-MOFs layer, leading to a photoanode of enhanced photocurrent and stability., (© 2020 Wiley-VCH GmbH.)

Collective cell migration plays a key role in tissue repair, metastasis, and development. Cellular tension is a vital mechanical regulator during the force-driven cell movements. However, the contribution and mechanism of cell-cell force interaction and energetic costs during cell migration are yet to be understood. Here, we attempted to unfold the mechanism of collective cell movement through quantification of the intercellular tension and energetic costs. The measurement of pN intercellular force is based on a "spring-like" DNA-probe and a molecular tension fluorescence microscopy. During the process of wound healing, the intercellular force along with the cell monolayer mainly originates from actin polymerization, which is strongly related to the cellular energy metabolism level. Intracellular force at different spatial regions of wound and the energetic costs of leader and follower cells were measured. The maximum force and energy consumption are mainly concentrated at the wound edge and dynamically changed along with different stages of wound healing. These results indicated the domination of leader cells other than follower cells during the collective cell migration.

An approach to the design of iridium(III)-contained polytetraphenylethene Pdots that could exhibit highly efficient electrochemiluminescence (ECL) was proposed. The relationships of ECL performance between the iridium complex-embedded and end-capped aggregation-induced emission (AIE) active Pdots in aqueous media were investigated for the first time. The iridium complexes with cyclometalated ligand 6-phenylphenanthridine (pphent) were incorporated into the copolymers by either embedding ( P0 , P2-P5 ) or end-capping ( P1 ) into the backbone via an ancillary 2,2'-bipyridine (bpy) ligand. Subsequently, the corresponding Pdots of P0 - P5 encapsulated with poly(styrene- co -maleicanhydride) could be obtained by the nanoprecipitation method. Compared to Pdots0 , Pdots2-Pdots5 with (pphent) 2 Ir(bpy) ( M1 ) complex embedding, as the iridium complex content increases, ECL signals were decreased in the order of Pdots0 > Pdots2 > Pdots3 > Pdots4 > Pdots5 ; whereas among these Pdots of P0 - P5 , Pdots1 with M1 complex end-capping exhibited the highest ECL efficiency (relative to a Ru(bpy) 3 2+ system of 18.9%) and 4.7-fold enhancement of the ECL signal compared to the parent Pdots of P0 , which was mainly attributed to the good film conductivity of the completely conjugated architectures, thus prompting the intramolecular electron transfer. This work opened new avenues for designing highly efficient ECL emitters.

Nanoelectrode arrays have been widely used in electroanalytical applications. The challenge is to develop low-cost and simple approaches to the fabrication of superuniform and ultrasmall nanoelectrode arrays for improving analytical performance and imaging resolution. Here, superuniform and high-density gold nanoelectrode arrays with tunable electrode diameters and interelectrode distances have been fabricated by electrodeposition, followed by a simple mechanical polishing process. The fabricated free-standing arrays have a high density (10 8 cm -2 ) of nanoelectrodes (60, 140, and 200 nm in diameter), and can be used as closed bipolar electrode arrays to image electrochemical heterogeneity with micrometer spatial resolution. With the help of a confocal microscope, individual nanoelectrodes can be visualized and resolved from the reflected light. Thus, the nanoelectrode arrays are promising in electrochemical imaging with high spatial resolution.

Triggered in response to external and internal ligands in cells and animals, redox homeostasis is transmitted via signal molecules involved in defense redox mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Cellular oxidation is not necessarily harmful per se, but its effects depend on the balance between the peroxidation and antioxidation cascades, which can vary according to the stimulus and serve to maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and redox control using IV infection as an example. We discuss the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS accumulation and the diversity of IV infection. We also summarize the potential anti-IV agents available currently that act by targeting redox biology/pathophysiology.

Objective: To assess the effectiveness of 1 dose varicella attenuated live vaccine (VarV) for healthy children aged 1-12 years in China and explore the application of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework in observational studies of vaccine effectiveness (VE). Methods: We searched studies about the VE of 1-dose VarV for children aged 1-12 years in China which published before 2019 and evaluated the quality of the studies by the Newcastle Ottawa Scale (NOS) table. We used Meta-analysis models to obtain the pooled 1-dose VE and that in subgroups by study design, outbreak or not, study quality and age of subjects. The evidences of VEs were rated by means of the GRADE system. Results: Thirty-two studies were included and the pooled 1-dose VE was 75% [95% confidence interval ( CI ): 68%-80%]. The VE of outbreak studies [VE=66% (95 %CI : 57%-73%)] was lower than non-outbreak studies [VE=85% (95 %CI : 78%-89%)], and the VE in <6 years old children [VE=84% (95 %CI :77%-89%)] was higher than that in ≥6 years old children [VE=60% (95 %CI : 51%-68%)]. There was no significant difference in VE among studies with different design and quality. The quality of the evidences of pooled 1-dose VE was"very low", which was downgraded in bias risk and inconsistency and not downgraded in indirectness, imprecision and publication bias. Conclusions: The 1-dose VarV can provide medium level protection for 1-12 years old children in China, but it will decrease significantly for ≥6 years old children, so it is suggested to implement the strategies of two-dose vaccination of VarV in children <6 years old. The GRADE framework can be used in the observational studies of VE and it is suggested that the technical guidelines of observational study should be worked out to improve the overall quality of evidence.

Objective: To analyze the changing trend of polio vaccine immunization effectiveness and vaccine titer in Beijing in 2012, 2014, 2016 and 2018 before and after the adjustment of polio vaccine immunization program strategy. Methods: According to the convenient sampling method,the vaccination clinics of Chaoyang and Yanqing Districts in 2012, Fengtai and Daxing Districts in 2014, Tongzhou and Pinggu Districts in 2016, Dongcheng and Shunyi Districts in 2018 were selected as monitoring points. A total of 292 children were selected 4-8 weeks after the completion of 3 doses polio vaccine basic immunization which were 3 doses of trivalent oral poliovirus vaccine（tOPV）schedule before the strategy adjustment in 2012-2014 and 1 dose of inactivated poliovirus vaccine (IPV) following 2 doses of bivalent oral poliovirus vaccine (bOPV) sequential schedule after the adjustment in 2016-2018. About 1.0 ml blood samples were collected to detect type Ⅰ and Ⅲ neutralizing poliovirus antibody. A total of 9 oral poliovirus vaccines (8 vaccines in 2012) were selected from different sources of vaccine storage every year to test the vaccine titer using random number method . Results: The [ M （ P 25 ， P 75 ）] age of 292 children was 5 (5, 6) months, and the ratio of male to female was 1.04 (149/143). In 2012, 2014, 2016 and 2018, 66,72,68 and 86 children were investigated respectively. After basic immunization, antibody positive rates for type Ⅰ and Ⅲ poliovirus were 100%, except 98.61% (71) for type Ⅰ poliovirus in 2014. The neutralizing antibody titer of type Ⅰ and Ⅲ poliovirus was higher in 2016 and 2018 than that in 2012 and 2014 ( P <0.001). The average titer of tOPV were (6.05±0.15) and (6.16±0.12) lgCCID 50 per dose in 2012 and 2014. The average titer of bOPV were (6.88±0.21) and (6.26±0.14) lgCCID 50 per 100 μl in 2016 and 2018 ( P <0.001). Conclusion: Before and after the adjustment of polio vaccine immunization strategy in Beijing, the basic immunization success rate of the IPV-bOPV sequential immunization schedule was good as well as full tOPV schedule. The level of polio antibody produced by the IPV-bOPV sequential immunization schedule was higher. After adjustment, bOPV titer in 2016 was significantly higher than those before adjustment, while bOPV titer decreased significantly in 2018.

We report a GNR-assisted NIR-activated tool that could open TRPV1 ion channels and regulate apoptotic protein expression, thereby inducing cell apoptosis, which might be an effective approach for cancer therapy.

The Jun dimerization protein 2 (Jdp2) is expressed predominantly in granule cell progenitors (GCPs) in the cerebellum, as was shown in Jdp2-promoter-Cre transgenic mice. Cerebellum of Jdp2-knockout (KO) mice contains lower number of Atoh-1 positive GCPs than WT. Primary cultures of GCPs from Jdp2-KO mice at postnatal day 5 were more resistant to apoptosis than GCPs from wild-type mice. In Jdp2-KO GCPs, the levels of both the glutamate‒cystine exchanger Sc7a11 and glutathione were increased; by contrast, the activity of reactive oxygen species (ROS) was decreased; these changes confer resistance to ROS-mediated apoptosis. In the absence of Jdp2, a complex of the cyclin-dependent kinase inhibitor 1 (p21 Cip1 ) and Nrf2 bound to antioxidant response elements of the Slc7a11 promoter and provide redox control to block ROS-mediated apoptosis. These findings suggest that an interplay between Jdp2, Nrf2, and p21 Cip1 regulates the GCP apoptosis, which is one of critical events for normal development of the cerebellum.

The aggregation-induced electrochemiluminescence (AIECL) of polyfluorene derivative nanoparticles containing tetraphenylethylene (TPE) in aqueous media is reported in this work. The TPE unit limits the intramolecular free rotation of phenyl rings, as well as the π-π stacking interactions of molecules, which significantly enhances ECL signal of the polyfluorene nanoparticles. With co-reactants of tri-n-propylamine (TPrA) and S 2 O 8 2- , the copolymer nanoparticles show visualized ECL emissions at both positive and negative potentials. The ECL efficiency of copolymer nanoparticles in solid state is 163% compared with that of standard ECL species, Ru(bpy) 3 2+ . And at negative potential, the ECL intensity of copolymer nanoparticles is even stronger with 6.5 times compared with that at positive potential. The ECL generation mechanisms are analyzed detailed by annihilation and co-reactant route transient ECL test (millisecond scale). This work provides a reference for the organic structure design for AIECL and shows promising potential in luminescent device and biological applications., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although many studies have shown that histamine and its signaling regulate energy homeostasis through the central nervous system, their roles in adipose tissues remain poorly understood. Here, we identified that the histamine H4 receptor (HrH4) was highly expressed in adipocytes at a level higher than that of the other three receptors (i.e., HrH1, HrH2, and HrH3). The HrH4 expression in adipocytes responded to cold through thermogenesis and lipolysis, supported by results from both mouse and cell models. When HrH4 expression was knocked down in the subcutaneous white adipose tissue (scWAT), browning and lipolysis effects triggered by cold were ablated, and the oxygen consumption was also lowered both at the normal and cold conditions. Moreover, mice exhibited browned scWAT, accelerated metabolic rates, and tolerance to hypothermia when 4-methylhistamine (4MH), a selective HrH4 agonist, was adjacently injected to the scWAT. Consistent with these findings, 4MH also triggered the browning and lipolytic effects in cultured C3H10T1/2 adipocytes. Mechanically, we demonstrated that p38/MAPK and ERK/MAPK pathways were involved in these processes. In conclusion, our findings have uncovered an effective role of HrH4 in adipose tissue browning.

A single gold nanopore with high surface enhanced Raman spectroscopy (SERS) activity is fabricated on the tip of a glass nanopipette. Polystyrene (PS) nanospheres can be recognized from the SERS spectrum while passing through the single nanopore.

Objective: Using data of health information system (HIS) of medical institutions to study the incidence and hospitalization of herpes zoster in three districts of Beijing. Methods: According to the different level of economic development and geographical features in Beijing, 3 districts of Xicheng, Changping and Miyun were chosen and all 110 medical institutions of the first level and above in the 3 districts are included in the survey. All the outpatient and inpatient herpes zoster cases in 2015 were retrospectively reviewed by HIS system. After distinguishing the reduplicated cases, Using the first outpatient case as a molecule and the resident population as denominator to estimate the annual incidence rate, as well as the annual hospitalization rate was estimated based on primary diagnostic hospitalized cases as molecule and the resident population as denominator. Results: A total of 32 313 primary visit outpatient cases were investigated, of which 18 360 cases (56.8%) were women and 20 923 cases (64.8%) were ≥50 years old. The overall estimated incidence of the 3 districts was 8.8‰ with an increase trends with age and reached to the highest in ≥80 years old (30.5/1 000). The incidence of Xicheng, Changping and Miyun districts are respectively 16.2‰, 4.0‰ and 5.7‰. A total of 701 primary visit inpatient cases were identified, of which 366 cases (52.2%) were women and 651 cases (92.9%) were ≥50 years old. The estimated annual hospitalization rate was 19.4/100 000, with the primary and secondary diagnostic hospitalization rate are respectively 5.9/100 000 (212 cases) and 13.5/100 000 (489 cases). The disease types of secondary diagnostic inpatient herpes zoster cases were as follows: cardiovascular disease (19.0%, 93 cases), stroke (14.5%, 71 cases), pneumonia/chronic obstructive pulmonary disease (14.1%, 69 cases), tumor (12.5%, 61 cases) and diabetes (5.7%, 28 cases). Conclusion: Most of the herpes zoster cases in Beijing are over 50 years old, and the incidence of female is slightly higher than male. This disease should become a public health issue of great concern.

Thermogenic beige fat improves metabolism and prevents obesity. Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis, whereas the activation of M1 macrophages, which play a major role in inflammation, impedes beige adipogenesis. Thus, the identification of factors that regulate adipose tissue macrophages (ATMs) will help clarify the mechanism involved in beiging. Here, we found that one of the secreted proteins in adipose tissue, namely, BMP4, alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting M1 macrophages. Mechanistically, the BMP4-stimulated p38/MAPK/STAT6/PI3K-AKT signalling pathway is involved. Meanwhile, BMP4 improved the potency of M2 macrophages to induce beige fat biogenesis. Considering that the overexpression of BMP4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity, these findings provide evidence that BMP4 acts as an activator of beige fat by targeting immuno-metabolic pathways.

This paper describes an electrochemiluminescence resonance energy transfer (ECL-RET) system using Ru(bpy) 3 2+ -doped silica nanoparticles (RuSi NPs) as the ECL donor and hollow Au nanocages as the ECL acceptor. Tetrahedron DNA (TD) was used to construct the biosensing interface and control the distance (4.8 nm) between the ECL donor-acceptor pairs. The surface plasmon resonance (SPR) nanostructures, Au nanocages were assembled via the hairpin based sandwich assay. Due to the well overlap between the plasmon absorption spectrum of Au nanocages (628 nm) and the ECL emission spectrum of RuSi NPs (620 nm), high efficient energy transfer could occur. Subsequent cyclic DNA amplification further increased the binding amount of Au nanocages. Since the ECL inhibition is closely related with the binding amount of Au nanocages, a general "signal-off" ECL bioassay could thus be tailored with high sensitivity. At the optimized conditions, this ECL-RET system performed well with great stability and repeatability for nucleic acid detection in the range from 1.0 fM to 10 pM. This work manifested the great promise of hollow Au nanocages for an ECL-RET biosensor that to the best of our knowledge has not been reported. We believe that it could inspire more interest in the design and development of numerous other SPR nanostructures for advanced ECL-RET biosensors.

Mass spectrometry imaging (MSI) is a crucial label-free method to distinguish the localization patterns in single cells. MALDI-TOF MS and ToF-SIMS are now bearing the responsibility. However, MALDI-TOF MS is limited to micron spatial resolution and ToF-SIMS suffers from severe molecular fragmentation. Here, we proposed a new MSI methodology of vacuum ultraviolet laser desorption/ionization (VUVDI) with high spatial resolution, achieving higher ion yields and less fragmentation compared with ToF-SIMS at submicron level. The fluorescence image and mass spectrum of VUVDI were obtained simultaneously. In addition, the adjustable laser fluence acquired selective detection for different molecular and fragmental ions, thus realizing molecular identification. Furthermore, MSIs of single cells with submicron craters were presented. These results suggest VUVDI is a potential mass spectrometry method that provides a soft ionization source and submicron spatial resolution for molecular analysis in life science.

Noble metal nanoparticles are promising catalysts in electrochemical reactions, while understanding the relationship between the structure and reactivity of the particles is important to achieve higher efficiency of electrocatalysis, and promote the development of single-molecule electrochemistry. Electrogenerated chemiluminescence (ECL) was employed to image the catalytic oxidation of luminophore at single Au, Pt, and Au-Pt Janus nanoparticles. Compared to the monometal nanoparticles, the Janus particle structure exhibited enhanced ECL intensity and stability, indicating better catalytic efficiency. On the basis of the experimental results and digital simulation, it was concluded that a concentration difference arose at the asymmetric bimetallic interface according to different heterogeneous electron-transfer rate constants at Au and Pt. The fluid slip around the Janus particle enhanced local redox reactions and protected the particle surface from passivation., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A paper-based SERS test strip combining strengths of paper chip and Raman active substrate was demonstrated to overcome challenges in spectroscopic sensing of complicated samples and realize quantitative detection of disease markers in whole blood. The precisely controlled Au NPs were not only capable of generating condensed hot spots on the fibers, but also enhanced the size exclusion effect of paper, resulting in the novel performance on both SERS detection and sample pretreatment. A biosensor for Mucin-1 is developed by equipping the Au NPs with aptamer. Combining all these merits, this small, cheap and portable test strip might find wide application in clinical diagnosis and health evaluation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor of the Journal. The retraction has been made because the Editor has been informed that a similar article containing the same research was submitted to another journal by other authors. The authors have admitted errors in drafting and submitting the paper and apologise for the mistakes., (Copyright © 2017. Published by Elsevier Ltd.)