A triple read-out visible biosensing platform based on multifunctional nanozyme and bipolar electrode for multi-mode detection and imaging of CEA.

In this paper, a proposal of closed bipolar electrode (BPE) and nanozyme based multi-mode biosensing platform is first presented. As a novel integrated chip, multi-mode-BPE (MMBPE) combines enzyme-linked immunoassay (ELISA), electrochemiluminescence (ECL), ECL imaging and light emitting diode (LED) imaging, enabling highly sensitive triple read-out visible detection of cancer embryonic antigen (CEA). The ECL probe Ab2@Au@Co3O4/CoFe2O4 hollow nanocubes (HNCs) with excellent peroxidase (POD) activity is introduced into the BPE cathode through immune adsorption. The Au@Co3O4/CoFe2O4 HNCs can increase the rate of hydrogen peroxide oxidation of TMB, thus promoting the reaction, and can be used for ELISA detection of CEA at different concentrations. The modification of the BPE sensing interface and reporting interface involved the introduction of the luminescent reagent Ru(bpy)32+ to the BPE anode. The decomposition rate of H2O2 increased under the catalytic action of Au@Co3O4/CoFe2O4 HNCs nanozyme, leading to an accelerated electron transfer rate in the MMBPE system and an enhanced ECL signal from Ru(bpy)32+. The LED imaging technology further provides a convenient and visible approach for CEA imaging in which no additional chemicals are needed. The integration of nanoenzymes as the catalytic core in MMBPE system provides impetus, while the combination of nanozymes with BPE expands the application of nanoenzymes in the field of biological analysis. The integration of intelligent chips with multiple modes of detection shows portable, miniaturized, and integrated excellent properties which meets the requirements of modern detection devices and thus offers a flexible approach for determination of nucleic acids, proteins, and cells.

Simultaneously improved photoluminescence, stability, and carrier transport of perovskite nanocrystals by post-synthetic perfluorobutanesulfonic acid treatment.

We report a post-synthetic treatment method based on perfluorobutanesulfonic acid (PFBA) to ameliorate the photophysical performance of perovskite nanocrystals. By virtue of the PFBA treatment, both the photoluminescence efficiency and stability of perovskite quantum dot-based colloidal solutions and the electrical conductivity of their close-packed films are simultaneously improved.

Curcumin-Loaded RH60/F127 Mixed Micelles: Characterization, Biopharmaceutical Characters and Anti-Inflammatory Modulation of Airway Inflammation.

Curcumin's ability to impact chronic inflammatory conditions, such as metabolic syndrome and arthritis, has been widely researched; however, its poor bioavailability limits its clinical application. The present study is focused on the development of curcumin-loaded polymeric nanomicelles as a drug delivery system with anti-inflammatory effects. Curcumin was loaded in PEG-60 hydrogenated castor oil and puronic F127 mixed nanomicelles (Cur-RH60/F127-MMs). Cur-RH60/F127-MMs was prepared using the thin film dispersion method. The morphology and releasing characteristics of nanomicelles were evaluated. The uptake and permeability of Cur-RH60/F127-MMs were investigated using RAW264.7 and Caco-2 cells, and their bioavailability and in vivo/vitro anti-inflammatory activity were also evaluated. The results showed that Cur-RH60/F127-MMs have regular sphericity, possess an average diameter smaller than 20 nm, and high encapsulation efficiency for curcumin (89.43%). Cur-RH60/F127-MMs significantly increased the cumulative release of curcumin in vitro and uptake by cells (p < 0.01). The oral bioavailability of Cur-RH60/F127-MMs was much higher than that of curcumin-active pharmaceutical ingredients (Cur-API) (about 9.24-fold). The treatment of cell lines with Cur-RH60/F127-MMs exerted a significantly stronger anti-inflammatory effect compared to Cur-API. In addition, Cur-RH60/F127-MMs significantly reduced OVA-induced airway hyperresponsiveness and inflammation in an in vivo experimental asthma model. In conclusion, this study reveals the possibility of formulating a new drug delivery system for curcumin, in particular nanosized micellar aqueous dispersion, which could be considered a perspective platform for the application of curcumin in inflammatory diseases of the airways.

An extra-erythrocyte role of haemoglobin body in chondrocyte hypoxia adaption.

Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive1,2. Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.

Association between ambient air pollutants and birthweight of singletons following assisted reproductive technologies.

OBJECTIVE: To investigate the associations between exposure to ambient air pollutants and birthweight following ART treatment. DESIGN: Retrospective cohort study. METHODS: We included 11,599 singletons derived from fresh cycles or frozen-thawed embryo transfer (FET) cycles between Jan 2013 and Dec 2019. Exposure to six air pollutants (SO2, NO2, CO, O3, PM2.5, and PM10) at patients` residences and the clinic site were estimated using the inverse distance weighting interpolation method based on data obtained from monitor sites. The daily mean levels of pollutants were estimated in potential exposure windows (the period from three months before treatment to oocyte retrieval, the period of ovarian stimulation, the period of in vitro culture, the period from embryo transfer to hCG test, the period of entire pregnancy, the 1st, 2nd, and 3rd trimester) were calculated. Generalized additive models adjusted for confounders including maternal age, BMI, and parity were used to evaluate the association between exposures and birthweight. Interaction of exposures and ART-associated factors, such as supraphysiologic estradiol and frozen-thawed, were explored in an XGboost model. MAIN OUTCOME MEASURES: Birthweight and z-score of singletons. RESULTS: In fresh cycles, O3 exposure during the period from three months before treatment to oocyte retrieval and SO2 exposure during in vitro culture at the ART clinic showed a linear association with birthweight (7.24, 95% CI: 1.18-13.31 g per 10 µg/m3 increase in O3; 25.92, 95% CI: 8.26-43.58 g per 10 µg/m3 increase in SO2, respectively). For patients receiving single blastocyst transfer with exposures below the China standard of 20 µg/m3, an increase of 10 µg/m3 in SO2 was associated with a 61.52 (95% CI: 1.13-121.91) g increase in birthweight. In FET cycles, no significant association was found between air pollution and birthweight. XGboost model did not reveal a strong interaction between the exposures and ART-related factors, except for the interactions between O3 exposure and BMI. However, none of the interactions reached a higher rank of importance. CONCLUSIONS: Air pollution exposure during ART treatment may affect the birthweight of the offspring.

Clinicopathological characteristics and prognostic analysis of breast cancer with a hormone receptor status of ER(-)/PR(+).

Background: It is unknown whether ER(-)/PR(+) breast cancer is an independent breast cancer subtype, how it differs from other subtypes, and what its significance is regarding treatment and prognosis. This study compared ER(-)/PR(+) breast cancer with other subtypes to better understand the biological characteristics and prognosis of ER(-)/PR(+) breast cancer, to guide clinical treatment and establish a theoretical foundation. Methods: We retrospectively analyzed data for patients diagnosed with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological characteristics of ER(-)/PR(+) breast cancer, including age, tumor size, lymph node status, HER-2 status, pathological type and histological grade, were compared with other types of breast cancer. A risk scoring system was developed based on independent risk factors influencing prognosis to predict the patient's prognosis, and a nomogram model was created to predict the patient's survival rate. Receiver operating characteristic curve (ROC) and calibration curve was used to evaluate the predictive performance of the nomogram. Results: The rates of T3-4, lymph node positivity, HER-2 positivity, infiltrating non-special pathological type, and G3 were significantly higher in ER(-)/PR(+) than in ER(+)/PR(+) cancer (p <0.001). ER(-)/PR(+) was similar to biological activity of ER(-)/PR(-) type. ER(-)/PR(+)/HER-2(+) patients had a better survival prognosis than ER(-)/PR(+) HER-2(-) patients (p<0.05). The prognosis of ER-/PR+ breast cancer was significantly associated with age, HER-2 status, and T stage. Conclusion: ER(-)/PR(+) breast cancer is more similar to ER(-)/PR(-) breast cancer than other breast cancer subtypes, with an early age of onset, a high proportion of infiltrating non-special types, a high histological grade, and a high HER-2 positivity rate. Whether HER-2 positivity can improve the prognosis of ER(-)/PR(+)breast cancer is worth further discussion. The risk scoring system we developed can effectively distinguish between high-risk and low-risk patients. The nomogram we created had a concordance index of 0.736, and the calibration curve showed good agreement between the predicted and observed outcomes.

Effects of high-risk human papillomavirus infection on P53, pRb, and survivin in lung adenocarcinoma-a retrospective study.

Objective: To observe the effects of high-risk human papillomavirus (HR-HPV) infection on P53, pRb, and survivin in lung adenocarcinoma (LUAD). Methods: The cancerous and cancer-adjacent tissues of 102 patients with LUAD from January 2020 to April 2022 were selected for the study. HR-HPV infection was detected by flow fluorescence method, and P53, pRb, and survivin protein expression was detected by immunohistochemical staining method. Statistical analysis was performed to determine the differences in the HR-HPV infection and the expression of P53, pRb, and survivin proteins between LUAD tissues and cancer-adjacent tissues; the correlation between HR-HPV infection and P53, pRb, and survivin protein expression in cancer tissues; and the correlation between HR-HPV infection and clinicopathological features of LUAD. Results: The infection rate of HR-HPV was higher in the LUAD tissues (28.43%) than in cancer-adjacent tissues (7.84%), and the difference was statistically significant (P < 0.05). The positive rates of P53 and survivin protein were higher in the LUAD group (33.33% and 67.16%, respectively) than in the cancer-adjacent group (3.92% and 11.73%, respectively), and the difference was statistically significant (P < 0.05). The positive rate of pRb protein was lower in the LUAD group (58.82%) than in the cancer-adjacent group (92.14%), and the difference was statistically significant (P < 0.05). The positive rates of P53 and survivin proteins were significantly higher in the HR-HPV LUAD group (58.62% and 86.21%, respectively) than in the non-HR-HPV LUAD group (41.38% and 67.12%, respectively), and the difference was statistically significant (P < 0.05). The expression rate of pRb protein was significantly lower in the HR-HPV LUAD group (37.93%) than in the non-HR-HPV LUAD group (67.12%), and the difference was statistically significant (P < 0.05). The expression of p53 and survivin protein was positively correlated with HR-HPV infection (r = 0.338 and 0.444, P < 0.05), whereas the expression of pRb protein was negatively correlated with HR-HPV infection (r =  - 0.268, P < 0.05). HR-HPV infection was not associated with gender, age, and smoking in patients with LUAD (P > 0.05). HR-HPV infection was associated with lymph node metastasis and clinical stage of LUAD (P < 0.05). Conclusions: HR-HPV infection was associated with lymph node metastasis and clinical stage of LUAD, which may be achieved by up-regulating p53 and survivin protein expression and down-regulating pRb protein expression.

Curcumin nanocrystals self-stabilized Pickering emulsion freeze-dried powder: Development, characterization, and suppression of airway inflammation.

Curcumin, a diketone compound extracted from turmeric's rhizome, is an effective anti-inflammatory drug with multiple pharmacological activities. However, its low oral bioavailability due to its low water solubility and permeability severely limits its clinical applications. Therefore, to enhance the oral bioavailability of curcumin, further enhance its anti-inflammatory effects, and improve its potential in the treatment of airway inflammation, a curcumin nanocrystalline self-stabilizing Pickering emulsion (Cur-NSSPE) was prepared through high-pressure homogenization. Next, Cur-NSSPE was dried using a freeze-drying method to produce Cur-NSSPE-FDP. The prepared Cur-NSSPE and Cur-NSSPE-FDP were physically characterized. The release behavior and transmembrane transport capability of Cur-NSSPE-FDP in vitro were evaluated. Pharmacokinetic study was performed to evaluate its oral bioavailability. The anti-inflammatory effects of Cur-NSSPE-FDP in vivo and in vitro were investigated using RAW 264.7 macrophage inflammation model induced by LPS and IFN-γ and asthma model in BALB/c mice induced by OVA. The average particle size of Cur-NSSPE was (163.66 ± 6.78) nm, and the average drug content was (2.78 ± 0.01) mg/mL. The transmission electron microscopy results showed that the droplets were spherical in shape with a relatively uniform size, and the curcumin nanocrystals formed a spherical core-shell structure wrapped at the interface of the droplets. The scanning electron microscopy showed that Cur-NSSPE-FDP was a neatly arranged, having loose and porous network structure. Furthermore, it can significantly improve the cumulative release of curcumin in vitro and improve oral bioavailability in rats, increase the uptake of RAW264.7 and Caco-2 cells, promote the transport of curcumin across Caco-2 cells, significantly inhibit the expression of inflammatory factors NO, IL-6, TNF-a, MDA, IgE and ICAM-1, and improve the expression of IL-10 and SOD. These results indicated that the curcumin nanocrystalline self-stabilizing Pickering emulsion-freeze dried powder improved the oral bioavailability of curcumin and enhanced its therapeutic effect in airway inflammation.

Clinical features of ischemic stroke in patients with nonvalvular atrial fibrillation combined with intracranial atherosclerotic stenosis.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) and intracranial atherosclerotic stenosis (ICAS) are major causes of ischemic stroke. Relatively few studies have focused on the risk factors and clinical features of ischemic stroke caused by NVAF combined with ICAS. METHOD: We retrospectively evaluated NVAF and/or ICAS in patients with acute ischemic stroke admitted within 72 h after stroke. All patients with acute ischemic stroke underwent diffusion-weighted magnetic resonance imaging (DWI), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and/or digital subtraction angiography (DSA). NVAF was detected by routine electrocardiogram or 24-h Holter examination, Doppler echocardiography, and contrast echocardiography of the right heart. RESULTS: Among the 635 enrolled patients, NVAF, ICAS, and NVAF+ICAS were diagnosed in 170 (26.77%), 255 (40.16%), and 210 (33.07%) patients, respectively. Patients in the NVAF+ICAS group were older (p < .001), specifically aged ≥75 years (p < .001). The admission time of the NVAF+ICAS group was shorter (p < .001) than that of the ICAS group. The admission NIHSS score of the NVAF group was higher than that of the NVAF+ICAS group (p < .001). HsCRP, NTpro-BNP, and LEVF levels were significantly different among the three groups (p < .001). NVAF+ICAS ischemic stroke occurred mainly in the right hemisphere (52.4%). CONCLUSION: NVAF with ICAS ischemic stroke is more likely to occur in older patients. Infarctions occurred mainly in the right cerebral hemisphere. Neurological deficits in NVAF are more severe than those in NVAF combined with ICAS and in simple ICAS ischemic strokes. HsCRP, LEVF, andNTpro-BNP seem to be closely associated with NVAF+ICAS ischemic stroke.

Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.

Members of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted functional characterization of amphioxus GSDME (BbGSDME) and found that it can be cleaved by distinct caspase homologs, yielding the N253 and N304 termini with distinct functions. The N253 fragment binds to cell membrane, triggers pyroptosis, and inhibits bacterial growth, while the N304 performs negative regulation of N253-mediated cell death. Moreover, BbGSDME is associated with bacteria-induced tissue necrosis and transcriptionally regulated by BbIRF1/8 in amphioxus. Interestingly, several amino acids that are evolutionarily conserved were found to be important for the function of both BbGSDME and HsGSDME, shedding new lights on the functional regulation of GSDM-mediated inflammation.

Ablation of Argonaute 2 in Schwann cells accelerates the progression of diabetic peripheral neuropathy.

Schwann cells (SCs) form myelin and provide metabolic support for axons, and are essential for normal nerve function. Identification of key molecules specific to SCs and nerve fibers may provide new therapeutic targets for diabetic peripheral neuropathy (DPN). Argonaute2 (Ago2) is a key molecular player that mediates the activity of miRNA-guided mRNA cleavage and miRNA stability. Our study found that Ago2 knockout (Ago2-KO) in proteolipid protein (PLP) lineage SCs in mice resulted in a significant reduction of nerve conduction velocities and impairments of thermal and mechanical sensitivities. Histopathological data revealed that Ago2-KO significantly induced demyelination and neurodegeneration. When DPN was induced in both wild-type and Ago2-KO mice, Ago2-KO mice exhibited further decreased myelin thickness and exacerbated neurological outcomes compared with wild-type mice. Deep sequencing analysis of Ago2 immunoprecipitated complexes showed that deregulated miR-206 in Ago2-KO mice is highly related to mitochondrial function. In vitro data showed that knockdown of miR-200 induced mitochondrial dysfunction and apoptosis in SCs. Together, our data suggest that Ago2 in SCs is essential to maintain peripheral nerve function while ablation of Ago2 in SCs exacerbates SC dysfunction and neuronal degeneration in DPN. These findings provide new insight into the molecular mechanisms of DPN.

SFTSV infection is associated with transient overproliferation of monoclonal lambda-type plasma cells.

The impairment of antibody-mediated immunity is a major factor associated with fatal cases of severe fever with thrombocytopenia syndrome (SFTS). By collating the clinical diagnosis reports of 30 SFTS cases, we discovered the overproliferation of monoclonal plasma cells (MCP cells, CD38+cLambda+cKappa-) in bone marrow, which has only been reported previously in multiple myeloma. The ratio of CD38+cLambda+ versus CD38+cKappa+ in SFTS cases with MCP cells was significantly higher than that in normal cases. MCP cells presented transient expression in the bone marrow, which was distinctly different from multiple myeloma. Moreover, the SFTS patients with MCP cells had higher clinical severity. Further, the overproliferation of MCP cells was also observed in SFTS virus (SFTSV)-infected mice with lethal infectious doses. Together, SFTSV infection induces transient overproliferation of monoclonal lambda-type plasma cells, which have important implications for the study of SFTSV pathogenesis, prognosis, and the rational development of therapeutics.

Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

Plasma Neurofilament Light Chain Predicts Mortality and Long-Term Neurological Outcomes in Patients with Intracerebral Hemorrhage.

Patients with intracerebral hemorrhage (ICH) often suffer from heterogeneous long-term neurological deficits, such as cognitive decline. Our ability to measure secondary brain injury to predict the long-term outcomes of these patients is limited. We investigated whether the blood neurofilament light chain (NfL) can monitor brain injury and predict long-term outcomes in patients with ICH. We enrolled 300 patients with first-episode ICH within 24 h recruited in the Chinese Cerebral Hemorrhage Mechanisms and Intervention study cohort from January 2019 to June 2020. Patients were prospectively followed up for 12 months. Blood samples were collected from 153 healthy participants. Plasma NfL levels determined using a single-molecule array revealed a biphasic increase in plasma NfL in ICH patients compared to healthy controls, with the first peak at around 24 h and a second elevation from day 7 through day 14 post-ICH. Plasma NfL levels were positively correlated with hemorrhage volume, National Institute of Health Stroke Scale, and Glasgow Coma Scale scores of ICH patients. Higher NfL concentration within 72 h after ictus was independently associated with 6- and 12-month worsened functional outcomes (modified Rankin Scale ≥ 3) and higher all-cause mortality. Magnetic resonance imaging and cognitive function evaluation were available for 26 patients at 6 months post-ICH, and NfL levels measured 7 days post-ictus correlated with decreased white matter fiber integrity and poor cognitive function at 6 months after stroke. These findings suggest that blood NfL is a sensitive marker for monitoring axonal injury post-ICH and can predict long-term functional ability and survival.

Influence of Two- and Three-Dimensional Engineering on the Trap State Distribution and Photophysical Properties of Lead Halide Perovskite Polycrystals.

Constructing a two- and three-dimensional (2D/3D) heterojunction structure on the surface of a 3D perovskite film, termed 2D/3D engineering, is effective in elevating the stability of perovskite polycrystal-based photovoltaic and photoelectronic devices; however, it remains controversial whether this protocol is favorable or detrimental to the device performance. Here, we prepare a series of 2D/3D perovskite films by post-treating the perovskite polycrystalline film with different concentrations of phenethylammonium iodide (PEAI). Systematic spectroscopy and electrochemical studies illustrate that PEAI can penetrate the 3D perovskite network and eliminate the intrinsic trap states of perovskite polycrystals, while the 2D perovskite nanosheets enriched on the top of the polycrystalline film may introduce additional trap states, which manipulate the photoluminescence performance and dynamics of the as-prepared perovskite films in an opposite manner. Based on this finding, the strategy of optimizing the photophysical properties of the host 3D perovskite through 2D/3D engineering is elaborated, paving the way for fabricating high-performance and high-stability perovskite polycrystalline films.

Long-term Pegylated GH for Children With GH Deficiency: A Large, Prospective, Real-world Study.

CONTEXT: The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. OBJECTIVE: This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. DESIGN: A prospective, observational, posttrial study (NCT03290235). SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. MAIN OUTCOMES MEASURES: Height SD score (Ht SDS) at 12, 24, and 36 months. RESULTS: A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. CONCLUSIONS: PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

Incidence of Childhood Type 1 Diabetes in Beijing During 2011-2020 and Predicted Incidence for 2025-2035: A Multicenter, Hospitalization-Based Study.

INTRODUCTION: China has a low incidence of type 1 diabetes mellitus (T1DM); however, based on the large population, the absolute numbers are high. Our aim was to assess the incidence of childhood T1DM in Beijing during 2011-2020, predicted incidence for 2025-2035, and to determine the incidence of diabetic ketosis or diabetic ketoacidosis (DK/DKA) in this population. METHODS: Data on patients aged less than 15 years of age with newly diagnosed T1DM between January 1, 2011 and December 31, 2020 was obtained from five tertiary hospitals in Beijing and retrospectively analyzed. RESULTS: In all, 636 children aged less than 15 years were diagnosed with T1DM during 2011-2020. The incidence of T1DM was 3.11-5.46 per 100,000 per year, with an average increase of 5.10% per year. The age-specific incidence for ages 0-4 years, 5-9 years, and 10-14 years was 2.97, 4.69, and 4.68 per 100,000 per year, respectively. The highest average annual increase (7.07%) in incidence was for the youngest age group. DK or DKA was present at the time of diagnosis of T1DM in 84.6% of patients. The age-specific incidence of T1DM among children aged less than 15 years was predicted to be 7.32, 11.4, and 11.52 per 100,000 in 2035 for ages 0-4 years, 5-9 years, and 10-14 years, respectively. CONCLUSIONS: The was a gentle increase in the incidence of childhood T1DM during 2011-2020 in Beijing. This increase is expected to continue for the next 15 years.

Circular RNAcirc_0076305 Promotes Cisplatin (DDP) Resistance of Non-Small Cell Lung Cancer Cells by Regulating ABCC1 Through miR-186-5p.

Background: Lung cancer is a social problem of increasing concern, and non-small cell lung cancer (NSCLC) accounts for 80%-85% incidence of lung cancer. Cisplatin (DDP) is reported as a first-line chemotherapy drug for NSCLC, but the resistance has became a main obstacle for NSCLC treatment. The high level of circular RNA circ_0076305 was related to the DDP resistance in NSCLC. However, the mechanism of circ_0076305 remains unclear in DDP resistance of NSCLC. Materials and Methods: Exosomes were detected by a transmission electron microscope and nanoparticle tracking analysis. The protein levels of CD63, CD81, P-glycoprotein (P-gp), Lung resistance-related protein, and ATP-binding cassette subfamily C member 1 (ABCC1) were examined by Western blot assay. Circ_0076305, microRNA-186-5p (miR-186-5p), and ABCC1 levels were tested by real-time quantitative polymerase chain reaction. DDP resistance was examined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay. The binding relationship between miR-186-5p and circ_0076305 or ABCC1 was predicted by circRNA interactome or starBase, and then verified by dual-luciferase reporter and RNA immunoprecipitation assays. The effect of circ_0076305 on DDP resistance in NSCLC was examined by xenograft tumor model in vivo. Results: Circ_0076305 was increased in NSCLC cell-derived exosomes, DDP-resistant NSCLC tissues and cells. Circ_0076305 knockdown elevated DDP sensitivity in vitro. Mechanically, circ_0076305 enhanced ABCC1 expression through sponging miR-186-5p, thus regulating DDP resistance of NSCLC. Furthermore, circ_0076305 silencing improved DDP sensitivity of NSCLC in vivo. Conclusion: The results from this study disclosed that circ_0076305 knockdown improved DDP sensitivity by the miR-186-5p/ABCC1 axis in NSCLC, hinting a potential circRNA-targeted therapy for NSCLC.

Low-Temperature Preparation of High-Quality Perovskite Polycrystalline Films via Crystallization Kinetics Engineering.

Preparation of lead halide perovskite polycrystalline films at a low annealing temperature is highly restricted by their intrinsically large crystallization activation energy, which hinders the conversion of the precursors/intermediates to perovskites and yields as-prepared polycrystals with tiny grain sizes and terrible crystal quality. Herein, we demonstrate through in-situ, real-time spectroscopic studies that both the nucleation and crystal growth kinetics can be improved without the need for a high annealing temperature by treating the film with thiourea, as accounted for by the reduced activation energy. As a consequence, the thiourea-treated perovskite polycrystalline film exhibits larger grain sizes and greater crystallinity than the untreated one. More importantly, owing to the synergistic effect of the promoted crystallization kinetics and the passivation of surface defects, the low-temperature prepared films treated with thiourea even present more prominent photophysical properties than those fabricated by using the conventional high-temperature method. The strategy of crystallization kinetics engineering proposed in this work paves the way for fabricating high-quality perovskite polycrystalline films in a low-temperature manner.

The influence of shorter red blood cell lifespan on the rate of HbA1c target achieved in type 2 diabetes patients with a HbA1c detection value lower than 7.

BACKGROUND: Variations in the red blood cell (RBC) lifespan can affect glycosylated hemoglobin (HbA1c) test values, but there is still a lack of evidence regarding how and to what degree the RBC lifespan influences HbA1c in the type 2 diabetes mellitus (T2DM) population owing to the restriction of traditional RBC lifespan-detection means. This study aimed to investigate the influence of RBC lifespan variation on HbA1c values in T2DM patients with a HbA1c detection value lower than 7%. METHODS: Patients with HbA1c <7% were divided into two groups: RBC lifespan <90 days and RBC lifespan ≥90 days. We collected blood glucose levels at seven time points for three consecutive months, assessed the HbA1c and glycosylated albumin levels, and calculated the hemoglobin glycation index (HGI) for each patient. RESULTS: There were no statistical differences in the HbA1c value between two groups, but the estimated glycosylated hemoglobin (eHbA1c) was significantly higher in patients with an RBC lifespan <90 days. The proportion of the eHbA1c ≥7% in the group with an RBC lifespan <90 days was significantly higher than the other group (33.87% vs. 12.50%, p < .01). Pearson analysis showed a significant negative correlation between RBC lifespan and the HGI in patients with T2DM (r = -0.348, p < .01). CONCLUSION: A reduced RBC lifespan in T2DM patients caused a noticeable underestimate of the blood glucose levels as presented by HbA1c detection value.