[Ru(dpp)3]Cl2-Embedded Oxygen Nano Polymeric Sensors: A Promising Tool for Monitoring Intracellular and Intratumoral Oxygen Gradients with High Quantum Yield and Long Lifetime.

Unraveling the intricacies between oxygen dynamics and cellular processes in the tumor microenvironment (TME) hinges upon precise monitoring of intracellular and intratumoral oxygen levels, which holds paramount significance. The majority of these reported oxygen nanoprobes suffer compromised lifetime and quantum yield when exposed to the robust ROS activities prevalent in TME, limiting their prolonged in vitro usability. Herein, the ruthenium-embedded oxygen nano polymeric sensor (Ru-ONPS) is proposed for precise oxygen gradient monitoring within the cellular environment and TME. Ru-ONPS (≈64±7 nm) incorporates [Ru(dpp)3]Cl2 dye into F-127 and crosslinks it with urea and paraformaldehyde, ensuring a prolonged lifetime (5.4 µs), high quantum yield (66.65 ± 2.43% in N2 and 49.80 ± 3.14% in O2), superior photostability (>30 min), and excellent stability in diverse environmental conditions. Based on the Stern-Volmer plot, the Ru-ONPS shows complete linearity for a wide dynamic range (0-23 mg L-1), with a detection limit of 10 µg mL-1. Confocal imaging reveals Ru-ONPS cellular uptake and intratumoral distribution. After 72 h, HCT-8 cells show 5.20±1.03% oxygen levels, while NIH3T3 cells have 7.07±1.90%. Co-culture spheroids display declining oxygen levels of 17.90±0.88%, 10.90±0.88%, and 5.10±1.18%, at 48, 120, and 216 h, respectively. Ru-ONPS advances cellular oxygen measurement and facilitates hypoxia-dependent metastatic research and therapeutic target identification.

Single Atom Ag Bonding Between PF3T Nanocluster and TiO2 Leads the Ultra-Stable Visible-Light-Driven Photocatalytic H2 Production.

Atomic Ag cluster bonding is employed to reinforce the interface between PF3T nano-cluster and TiO2 nanoparticle. With an optimized Ag loading (Ag/TiO2 = 0.5 wt%), the Ag atoms will uniformly disperse on TiO2 thus generating a high density of intermediate states in the band gap to form the electron channel between the terthiophene group of PF3T and the TiO2 in the hybrid composite (denoted as T@Ag05-P). The former expands the photon absorption band width and the latter facilitates the core-hole splitting by injecting the photon excited electron (from the excitons in PF3T) into the conduction band (CB) of TiO2. These characteristics enable the high efficiency of H2 production to 16 580 µmol h-1 g-1 and photocatalysis stability without degradation under visible light exposure for 96 h. Compared to that of hybrid material without Ag bonding (TiO2@PF3T), the H2 production yield and stability are improved by 4.1 and 18.2-fold which shows the best performance among existing materials in similar component combination and interfacial reinforcement. The unique bonding method offers a new prospect to accelerate the development of photocatalytic hydrogen production technologies.

Electron Injection via Interfacial Atomic Au Clusters Substantially Enhance the Visible-Light-Driven Photocatalytic H2 Production of the PF3T Enclosed TiO2 Nanocomposite.

A hybrid composite of organic-inorganic semiconductor nanomaterials with atomic Au clusters at the interface decoration (denoted as PF3T@Au-TiO2 ) is developed for visible-light-driven H2 production via direct water splitting. With a strong electron coupling between the terthiophene groups, Au atoms and the oxygen atoms at the heterogeneous interface, significant electron injection from the PF3T to TiO2 occurs leading to a quantum leap in the H2 production yield (18 578 µmol g-1 h-1 ) by ≈39% as compared to that of the composite without Au decoration (PF3T@TiO2 , 11 321 µmol g-1 h-1 ). Compared to the pure PF3T, such a result is 43-fold improved and is the best performance among all the existing hybrid materials in similar configurations. With robust process control via industrially applicable methods, it is anticipated that the findings and proposed methodologies can accelerate the development of high-performance eco-friendly photocatalytic hydrogen production technologies.

Highly Efficient MAPbI3 -Based Quantum Dots Exhibiting Unusual Nonblinking Single Photon Emission at Room Temperature.

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

Highly Luminescent Earth-Benign Organometallic Manganese Halide Crystals with Ultrahigh Thermal Stability of Emission from 4 to 623 K.

The phosphor-converted light-emitting diode (PC-LED) has become an indispensable solid-state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare-earth elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2 (XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron-phonon coupling and the unique rigid crystal structure of MnI2 (XanPO) over the whole temperature range based on the temperature-dependent photoluminescence (PL) and single crystal X-ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC-LEDs with a power efficacy of 102.5 lm W-1 , an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m-2 are fabricated by integrating MnI2 (XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2 (XanPO) in both micro-LEDs and organic light-emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.

Two new antimicrobial monoterpenoid indole alkaloids from the roots of Rauvolfia yunnanensis.

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.

Albicanol inhibits the toxicity of profenofos to grass carp hepatocytes cells through the ROS/PTEN/PI3K/AKT axis.

Profenofos (PFF) as an environmental pollutant seriously harms the health of aquatic animals, and even endangers human safety through the food chain. Albicanol, a sesquiterpenoid extraction from the Dryopteris fragrans, has previously been shown to effectively exhibit anti-aging, anti-oxidant, and antagonize the toxicity of heavy metals. However, the mechanism of hepatocyte toxicity caused by PFF and the role that Albicanol plays in this process are still unclear. In this study, a PFF poisoning model was established by treating grass carp hepatocytes cells with PFF (150 µM) for 24 h The results of AO/EB staining, Tunel staining and flow cytometry showed that the proportion of apoptotic liver cells increased significantly after exposure. The results of ROS staining show that compared with the control group, ROS levels and PTEN/PI3K/AKT-related gene expression were up-regulated after PFF exposure. RT-qPCR and Western blotting results showed that the expression of PTEN/PI3K/AKT related genes was up-regulated. These results indicate that PFF can induce oxidative stress in hepatocytes and inhibit the phosphorylation of AKT. We further found that the expressions of Bax, CytC, Caspase-3, Caspase-9, Caspase-8 and TNFR1 after PFF exposure were significantly higher than those of the control group, and Bcl-2/Bax was significantly lower than that of the control group. These results indicate that PFF can induce oxidative stress in hepatocytes and inhibit the phosphorylation of AKT and activate mitochondrial apoptosis. Using Albicanol (5 × 10-5 µg mL-1) can significantly reduce the above-mentioned effects of PFF exposure on grass carp hepatocytes cells. In summary, Albicanol inhibits PFF-induced apoptosis by regulating the ROS/PTEN/PI3K/AKT pathway.

A microscope-assisted endoscopic transcanal transpromontorial approach for vestibular schwannoma resection: a preliminary report.

OBJECTIVE: To evaluate the feasibility of a microscope-assisted endoscopic transcanal transpromontorial approach (METTA) for the removal of small vestibular schwannomas (VS) limited to the internal auditory canal (IAC), and introduce a modification without external auditory canal (EAC) closure. METHODS: Between August 2018 and February 2019, seven patients with intrameatal VS underwent surgery in our center, endoscopic transcanal transpromontorial approach was applied in the first 2 patients and the rest 5 patients were operated via METTA. Treatment outcomes including efficacy of tumor resection, facial nerve outcome, operation time and post-operative course were recorded and analyzed. RESULTS: All seven patients were pathologically confirmed to have intrameatal VS. Total tumor removal was achieved in all cases. Two patients experienced cerebrospinal fluid leakage which resolved spontaneously within 5 days. The average operation time was 161.41 ± 18.42 min. All patients presented normal facial nerve function 1 month after surgery. CONCLUSION: The METTA was effective in the removal of intrameatal VS. It can be an alternative surgical option for intrameatal VS with no serviceable hearing.

Targeting the KDM4B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate cancer.

The histone demethylase KDM4B functions as a key co-activator for the androgen receptor (AR) and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 methylation marks. Constitutively active androgen receptor confers anti-androgen resistance in advanced prostate cancer. However, the role of KDM4B in resistance to next-generation anti-androgens and the mechanisms of KDM4B regulation are poorly defined. Here we found that KDM4B is overexpressed in enzalutamide-resistant prostate cancer cells. Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next-generation AR-targeted therapy. Inhibition of KDM4B significantly inhibited prostate tumor cell growth in xenografts, and improved enzalutamide treatments through suppression of c-Myc. Clinically, KDM4B expression was found upregulated and to correlate with prostate cancer progression and poor prognosis. Our results revealed a novel mechanism of anti-androgen resistance via histone demethylase alteration which could be targeted through inhibition of KDM4B to reduce AR-dependent c-Myc expression and overcome resistance to AR-targeted therapies. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Cyclophilin BcCyp2 Regulates Infection-Related Development to Facilitate Virulence of the Gray Mold Fungus Botrytis cinerea.

Cyclophilin (Cyp) and Ca2+/calcineurin proteins are cellular components related to fungal morphogenesis and virulence; however, their roles in mediating the pathogenesis of Botrytis cinerea, the causative agent of gray mold on over 1000 plant species, remain largely unexplored. Here, we show that disruption of cyclophilin gene BcCYP2 did not impair the pathogen mycelial growth, osmotic and oxidative stress adaptation as well as cell wall integrity, but delayed conidial germination and germling development, altered conidial and sclerotial morphology, reduced infection cushion (IC) formation, sclerotial production and virulence. Exogenous cyclic adenosine monophosphate (cAMP) rescued the deficiency of IC formation of the ∆Bccyp2 mutants, and exogenous cyclosporine A (CsA), an inhibitor targeting cyclophilins, altered hyphal morphology and prevented host-cell penetration in the BcCYP2 harboring strains. Moreover, calcineurin-dependent (CND) genes are differentially expressed in strains losing BcCYP2 in the presence of CsA, suggesting that BcCyp2 functions in the upstream of cAMP- and Ca2+/calcineurin-dependent signaling pathways. Interestingly, during IC formation, expression of BcCYP2 is downregulated in a mutant losing BcJAR1, a gene encoding histone 3 lysine 4 (H3K4) demethylase that regulates fungal development and pathogenesis, in B. cinerea, implying that BcCyp2 functions under the control of BcJar1. Collectively, our findings provide new insights into cyclophilins mediating the pathogenesis of B. cinerea and potential targets for drug intervention for fungal diseases.

The ubiquitinase ZFP91 promotes tumor cell survival and confers chemoresistance through FOXA1 destabilization.

The forkhead box A1 (FOXA1), one of the forkhead class of DNA-binding proteins, functions as a transcription factor and plays a vital role in cellular control of embryonic development and cancer progression. Downregulation of FOXA1 has reported in several types of cancer, which contributes to cancer cell survival and chemoresistance. However, the mechanism for FOXA1 downregulation in cancer remains unclear. Here, we report that the ubiquitination enzyme zinc finger protein 91 (ZFP91) ubiquitinates and destabilizes FOXA1, which promotes cancer cell growth. High level of ZFP91 expression correlates with low level of FOXA1 protein in human gastric cancer (GC) cell lines and patient samples. Furthermore, ZFP91 knockdown reduces FOXA1 polyubiquitination, which decreases FOXA1 turnover and enhances cellular sensitivity to chemotherapy. Taken together, our findings reveal ZFP91-FOXA1 axis plays an important role in promoting GC progression and provides us a potential therapeutic intervention in the treatment of GC.

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy.

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.

The H3K4 demethylase Jar1 orchestrates ROS production and expression of pathogenesis-related genes to facilitate Botrytis cinerea virulence.

Histone 3 Lysine 4 (H3K4) demethylation is ubiquitous in organisms, however the roles of H3K4 demethylase JARID1(Jar1)/KDM5 in fungal development and pathogenesis remain largely unexplored. Here, we demonstrate that Jar1/KDM5 in Botrytis cinerea, the grey mould fungus, plays a crucial role in these processes. The BcJAR1 gene was deleted and its roles in fungal development and pathogenesis were investigated using approaches including genetics, molecular/cell biology, pathogenicity and transcriptomic profiling. BcJar1 regulates H3K4me3 and both H3K4me2 and H3K4me3 methylation levels during vegetative and pathogenic development, respectively. Loss of BcJAR1 impairs conidiation, appressorium formation and stress adaptation; abolishes infection cushion (IC) formation and virulence, but promotes sclerotium production in the ΔBcjar1 mutants. BcJar1 controls reactive oxygen species (ROS) production and proper assembly of Sep4, a core septin protein and virulence determinant, to initiate infection structure (IFS) formation and host penetration. Exogenous cAMP partially restored the mutant appressorium, but not IC, formation. BcJar1 orchestrates global expression of genes for ROS production, stress response, carbohydrate transmembrane transport, secondary metabolites, etc., which may be required for conidiation, IFS formation, host penetration and virulence of the pathogen. Our work systematically elucidates BcJar1 functions and provides novel insights into Jar1/KDM5-mediated H3K4 demethylation in regulating fungal development and pathogenesis.

ICP-MS based on-line monitoring of Pu-239 airborne concentration.

An online monitoring technology of Pu-239 aerosol based on aerosol direct introduction device, membrane desolvation nebuliser and ICP-MS was established for workplaces of reprocessing plants. Briefly, 0.8 l min-1 Pu-239 aerosol from the workplace was introduced into the aerosol direct introduction device where the air was replaced by Argon, and then the aerosol was introduced into the ICP-MS for measurement. To determine the activity of Pu-239 aerosol, 1.10E-3 Bq ml-1 Pu-242 standard solution generated by a membrane desolvation nebuliser was used. The introduction efficiency of the nebuliser was determined by sampling the aerosol generated from the nebuliser with Lead Standard Solution by glass fiber filter, which was (26.82 ± 3.33) %. The mass bias between Pu-239 and Pu-242 for the ICP-MS measurement was determined by Pu-239 and Pu-242 standard solutions generated by the nebuliser, and mass discrimination correction factor for Pu-239/Pu-242 was 0.972 ± 0.010. The limit of detection (LOD) and limit of quantification (LOQ) of this system were calculated according to the ISO 20 899:2018, which were 2.24E-05 Bq m-3 and 7.45E-05 Bq m-3 with 1 min measurement. The main interference which was from U-238 was determined by U-238 standard solution generated by the nebuliser, and the interferences of U-238 to 239 was (8.50 ± 1.05) E-05. According to the counts of U-238 from several workplaces of reprocessing plant where this system was tested, 239 counts rate from the interferences of U-238 of those workplaces were at the same level of the system background counts, which meant that the LOD above was suitable for those places.

STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling.

Yes-associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. Moreover, we revealed that STUB1 ubiquitinates YAP1 at the K280 site by K48-linked polyubiquitination, which in turn increases YAP1 turnover and promotes cellular chemosensitivity. Overall, our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions.

Testing the methodology for a dosimetric end-to-end audit of IMRT/VMAT: results of IAEA multicentre and national studies.

Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented.Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations.Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within ±5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria.Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.

The key gluconeogenic gene PCK1 is crucial for virulence of Botrytis cinerea via initiating its conidial germination and host penetration.

The process of initiation of host invasion and survival of some foliar phytopathogenic fungi in the absence of external nutrients on host leaf surfaces remains obscure. Here, we demonstrate that gluconeogenesis plays an important role in the process and nutrient-starvation adaptation before the pathogen host invasion. Deletion of phosphoenolpyruvate carboxykinase gene BcPCK1 in gluconeogenesis in Botrytis cinerea, the causative agent of grey mould, resulted in the failure of the ΔBcpck1 mutant conidia to germinate on hard and hydrophobic surface and penetrate host cells in the absence of glucose, reduction in conidiation and slow conidium germination in a nutrient-rich medium. The wild-type and ΔBcpck1 conidia germinate similarly in the presence of glucose (higher concentration) as the sole carbon source. Conidial glucose-content should reach a threshold level to initiate germination and host penetration. Infection structure formation by the mutants displayed a glucose-dependent fashion, which corresponded to the mutant virulence reduction. Exogenous glucose or complementation of BcPCK1 completely rescued all the developmental and virulence defects of the mutants. Our findings demonstrate that BcPCK1 plays a crucial role in B. cinerea pathogenic growth and virulence, and provide new insights into gluconeogenesis mediating pathogenesis of plant fungal pathogens via initiation of conidial germination and host penetration.

Pressure Welding of Silver Nanowires Networks at Room Temperature as Transparent Electrodes for Efficient Organic Light-Emitting Diodes.

In this work, polymethylmethacrylate (PMMA) as a superior mediate for the pressure welding of silver nanowires (Ag NWs) networks as transparent electrodes without any thermal treatment is demonstrated. After a pressing of 200 kg cm-2 , not only the sheet resistance but also the surface roughness of the PMMA-mediated Ag NWs networks decreases from 2.6 kΩ sq-1 to 34.3 Ω sq-1 and from 76.1 to 12.6 nm, respectively. On the other hand, high transparency of an average transmittance in the visible wavelengths of 93.5% together with a low haze value of 2.58% can be achieved. In terms of optoelectronic applications, the promising potential of the PMMA-mediated pressure-welded Ag NWs networks used as a transparent electrode in a green organic light-emitting diode (OLED) device is also demonstrated. In comparison with the OLED based on commercial tin-doped indium oxide electrode, the increments of power efficiency and external quantum efficiency (EQE) from 80.1 to 85.9 lm w-1 and 19.2% to 19.9% are demonstrated. In addition, the PMMA-mediated pressure welding succeeds in transferring Ag NWs networks to flexible polyethylene naphthalate and polyimide substrates with the sheet resistance of 42 and 91 Ω sq-1 after 10 000 times of bending, respectively.

Impact of an intelligent chronic disease management system on patients with type 2 diabetes mellitus in a Beijing community.

BACKGROUND: Rapid demographic and economic changes have made chronic disease the number one health issue in China, contributing to more than 80% of the country's 10.3 million annual deaths and nearly 70% of its total disease burden (Wang et al., Toward a Healthy and Harmonious Life in China: Stemming the Rising Tide of Non-Communicable Diseases, 2011; Yip and Hsiao, Lancet 384: 805-18, 2014). Diabetes is a major contributor to the chronic disease burden and is experienced by nearly 11% of the adult population of China (Yang et al., N Engl J Med 362:1090-101, 2010). In response to the challenges of chronic disease, the Chinese government initiated comprehensive health care reforms nationwide in 2009. A key measure was a hierarchical diagnosis and treatment system for monitoring and reducing chronic diseases and improving the community health service system (Barber et al., Health Policy Plan 29:367-78, 2014). Primary hospitals, such as community health service centers, are the main gatekeepers for management of diabetes and other chronic diseasesin China. In recognition of the need for a more patient-centered approach, the Chinese government has piloted a program incorporating methods of diabetes self-management for chronic care: the Happy Life Club (Browning et al., Front in Public Health 2:181, 2015). This program is modeled on a similar program developed in Australia (Kelly et al., Aust J Prim Health 9:186-9, 2003). The ICDMS is an important tool in the implementation of patient-centered programs targeting chronic health issues, and its success is determined by factors, such as frequent contact between patients and doctors and effective website training for patients. This retrospective study used de-identified data from the Fangzhuang (Beijing) intelligent chronic disease management system (ICDMS) database to evaluate the effect of an intelligent chronic disease management system on selected Beijing community patients who have type 2 diabetes mellitus (T2DM). METHODS: A comparative study before and after ICDMS implementation was performed to evaluate the effect of ICDMS on the rates of follow-up and laboratory examinations, measurement rates of blood glucose and lipids, glycosylated hemoglobin (HbA1c) and blood lipid levels, as well as the corresponding health parameters. Continuous variables and categorical variables were analyzed using paired t-test and McNemar's tests, respectively. RESULTS: A total of 2451 T2DM patients met inclusion/exclusion criteria. Compared with the pre-index period, the laboratory examination, rates of blood glucose and blood lipids increased significantly in the post-index period (p < 0.001). Triglyceride (TC) levels decreased significantly from 5.22 mmol/L to 5.11 mmol/L (p < 0.05), and high density lipoprotein-cholesterol (HDL-C) levels increased significantly from 1.35 mmol/L to 1.48 mmol/L (p < 0.05). The control rate of TC increased from 24.86 to 29.76% (p = 0.079). The control rate of low density lipoprotein-cholesterol (LDL-C) increased from 12.16 to 13.97% (p = 0.421), while the control rate of HDL-C increased significantly from 68.60 to 78.77%. Importantly, Compared with the patients with HbA1C above 7% in the pre-index period, the mean HbA1c decreased significantly from 7.84 to 6.94%((p < 0.001) in the post-index period, and the control rate of HbA1c was 57.43%. CONCLUSIONS: The intelligent chronic disease management system is an effective tool in the management of T2DM and should be promoted by the Community Health Service Center in China as well as in other developing countries.

Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.

Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.