Dual-Capped Helical Interface Mimics.

Disruption of protein-protein interactions is medicinally important. Interface helices may be mimicked in helical probes featuring enhanced rigidities, binding to protein targets, stabilities in serum, and cell uptake. This form of mimicry is dominated by stapling between side chains of helical residues: there has been less progress on helical N-caps, and there were no generalizable C-caps. Conversely, in natural proteins, helicities are stabilized and terminated by C- and N-caps but not staples. Bicyclic caps previously introduced by us enable interface helical mimicry featuring rigid synthetic caps at both termini in this work. An unambiguously helical dual-capped system proved to be conformationally stable, binding cyclins A and E, and showed impressive cellular uptake. In addition, the dual-capped mimic was completely resistant to proteolysis in serum over an extended period when compared with "gold standard" hydrocarbon-stapled controls. Dual-capped peptidomimetics are a new, generalizable paradigm for helical interface probe design.

Kir2.1 channel regulates macrophage polarization via the Ca2+/CaMK II/ERK/NF-κB signaling pathway.

Macrophage polarization plays a key role in the inflammatory response. Various ion channels expressed in macrophages have been documented, but very little is known about their roles in macrophage polarization. We found that knockdown or blockade of the Kir2.1 (also known as KCNJ2) channel significantly inhibited M1 macrophage polarization, but promoted M2 macrophage polarization. Lipopolysaccharide (LPS)-induced M1 polarization was also remarkably suppressed in high extracellular K+ solutions (70 mM K+), and this inhibition was partially abolished by adding Ca2+ to the culture medium. Ca2+ imaging showed that Ca2+ influx was dependent on the hyperpolarized membrane potential generated by the Kir2.1 channel. The upregulation of phospho (p)-CaMK II, p-ERK, and p-NF-κB proteins in macrophages from the RAW264.7 cell line that were stimulated with LPS was significantly reversed by blocking the Kir2.1 channel or culturing the cells with 70 mM K+ medium. Furthermore, in vivo studies showed that mice treated with a Kir2.1 channel blocker were protected from LPS-induced peritonitis. In summary, our data reveal the essential role of the Kir2.1 channel in regulating macrophage polarization via the Ca2+/CaMK II/ERK/NF-κB signaling pathway.

Supercapacitor Performance of Sulfonyldibenzene Derivative-Functionalized Graphene Aerogel.

3D aerogels incorporating functionalized reduced graphene oxide (SUL/rGO) were prepared as a hydrothermal method utilizing graphene oxide (GO) and a sulfonyldibenzene derivative (SUL) as raw materials. The aromatic compound SUL, which contains hydroxyl and sulfonyl groups, was bonded to reduced graphene oxide (rGO) through π-π connections. The obtained composite material exhibited porosity within its structure with improved hydrophilicity, along with excellent electrochemical characteristics. This improvement was ascribed to the specific rGO structure, as well as the pseudocapacitance inherent in SUL, both of which synergistically contribute to improvement in the characteristics of the prepared electrode materials. Also, an analysis was performed employing density functional theory from which the density of states and adsorption energy of SUL on the surface of rGO were computed to further investigate the charge storage process within the prepared composite. The prepared SUL/rGO-2 electrode exhibited the highest specific capacitance value of 388 F/g at a current density equal to 1 A/g. The constructed symmetrical supercapacitor, SUL/rGO-2//SUL/rGO-2, attained an energy density value of 14.55 Wh/kg at a power density equal to 350 W/kg with an exceptional galvanostatic charge-discharge (GCD) cyclic stability equal to 91% following 10 000 cycles. Therefore, this review presents a novel functionalized graphene-based material incorporating hydroxyl and sulfonyl groups, which holds promise in future energy storage applications.

Resveratrol Delays Diabetic Cardiomyopathy Fibrosis by Regulating Mitochondrial Autophagy.

Objective: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. Methods: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice. Western blot staining was performed on myocardial tissues to assess the protein expression levels of p-AMPK, SIRT1, SIRT3, p22, GP91, p-IRE1α, XBP1s PINK, Parkin, LC3I, and Beclin. Mouse myocardial cells were cultured in vitro and intervened with a high-sugar high-fat diet, resveratrol, and GSK690693 (an AMPK inhibitor) to observe the protein expression levels of p-AMPK, p22, XBP1s, and PINK in mouse myocardial cells in each group. Results: Results from echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy showed that resveratrol administration alleviated cardiac damage, myocardial fibrosis, myocardial cell apoptosis, and mitochondrial autophagy in DCM mice. Resveratrol administration promoted the expression of phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1), and sirtuin 3 (SIRT3) in the myocardial tissue of mice, while lowering the elevated protein expression levels of p22 subunit (p22), guanine nucleotide-binding protein q polypeptide 1 (GP91), phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1α), X-box binding protein 1 spliced form (XBP1s), PTEN-induced putative kinase 1 (PINK), Parkin, microtubule-associated proteins light chain 3 isoform I (LC3I), and Beclin (Bcl-2 interacting protein) caused by DCM. GSK690693 (an AMPK inhibitor) suppressed the expression of p-AMPK, SIRT1, and SIRT3 and enhanced the protein expression of p22, XBP1s, and PINK. Conclusion: Resveratrol postpones dilated cardiomyopathy fibrosis by regulating the mitochondrial autophagy response through the AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1)-mediated inositol-requiring enzyme 1 alpha (IRE1α)/PTEN-induced putative kinase 1 (PINK) signaling pathway.

Effect of photodynamic therapy mediated by hematoporphyrin derivatives on small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells.

To investigate the effects of photodynamic therapy (PDT) mediated by hematoporphyrin derivatives (HPD) on the proliferation of small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells. H446 cells and BEAS-2B cells were cultured in vitro with different concentrations of HPD(0, 5, 10, 12, 15, 20 µg/mL) for 4 h, and then irradiated with 630 nm laser with different energy densities (0, 25, 50, 75, 100 mW/cm2). Cell viability of H446 cells and BEAS-2B cells were detected by CCK8 assay. The cell apoptosis was observed with Annexin V-FTTC/PI double staining and Hoechst 33258. The RT-PCR examination was applied to detect the transcriptional changes of the mRNA of Bax、Bcl-2, and Caspase-9. The results of CCK8 showed that when the HPD was 15 µg/mL and the laser power density reached 50 mW/cm2, the cell viability was significantly decreased compared with the black control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cell density was reduced, and apoptotic cells increased. Flow cytometry assay revealed that the apoptotic rates of the HPD-PDT group of H446 cells and BEAS-2B cells were significantly different from those of the blank control group. The RT-PCR examination showed that the expression levels of Bax and Caspase-9 mRNA in the HPD-PDT group were up-regulated, while the expression levels of Bcl-2 mRNA were down-regulated significantly. HPD-PDT can inhibit H446 cells and BEAS-2B cells growth. The mechanism may be related to up-regulating the expression levels of Bax and Caspase-9 mRNA and down-regulating the expression levels of Bcl-2 mRNA.

PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition yields differential cellular responses in multiple tumor models due to redundancy in cell cycle. We investigate whether the differential requirements of CDKs in multiple cell lines function as determinant of response to pharmacological agents that target these kinases. METHODS: We utilized proteolysis-targeted chimeras (PROTACs) that are conjugated with palbociclib (Palbo-PROTAC) to degrade both CDK4 and CDK6. FN-POM was synthesized by chemically conjugating pomalidomide moiety with a multi-kinase inhibitor, FN-1501. Patient derived PDAC organoids and PDX model were utilized to investigate the effect of FN-POM in combination with palbociclib. RESULTS: Palbo-PROTAC mediates differential impact on cell cycle in different tumor models, indicating that the dependencies to CDK4 and 6 kinases are heterogenous. Cyclin E overexpression uncouples cell cycle from CDK4/6 and drives resistance to palbo-PROTAC. Elevated expression of P16INK4A antagonizes PROTAC-mediated degradation of CDK4 and 6. FN-POM degrades cyclin E and CDK2 and inhibits cell cycle progression in P16INK4A-high tumor models. Combination of palbociclib and FN-POM cooperatively inhibit tumor cell proliferation via RB activation. CONCLUSION: Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach.

The natural flavone acacetin protects against high-fat diet-induced lipid accumulation in the liver via the endoplasmic reticulum stress/ferroptosis pathway.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. To date, no medication has been approved to treat NAFLD. In this study, we evaluated the therapeutic effect of the natural flavone acacetin on high-fat diet (HFD)-induced NAFLD in mice and the underlying mechanisms. We found that acacetin (10, 20, 50 mg/kg/day) suppressed the increase in body weight, serum total cholesterol, triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in mice fed with HFD with a dose-dependent manner. Hepatic lipid accumulation, iron overload, and lipid peroxidation were significantly alleviated by acacetin. Quantitative PCR and western blotting revealed that acacetin inhibited endoplasmic reticulum (ER) stress, ferroptosis, and expressions of lipid acid synthesis-related genes in the livers of HFD mice. Similar results were observed in HepG2 cells treated with oleic acid and lipopolysaccharide. The suppressive effects of acacetin on triglycerides and expression of lipid acid synthesis genes were abolished by ER stress and the ferroptosis activators, erastin or TU. Interestingly, the action of TU was more potent than that of erastin. Treatment with the ER stress inhibitor GSK and the ferroptosis inhibitor Fer-1 revealed that ER stress was the upstream signal of ferroptosis for hepatic lipid accumulation. These findings suggest the protective effect of acacetin against lipid accumulation via suppressing ER stress and ferroptosis and provide evidence that ER stress is an upstream signal of ferroptosis in lipid accumulation. Acacetin may be a promising candidate agent for NAFLD treatment.

Functional Potassium Channels in Macrophages.

Macrophages are the predominant component of innate immunity, which is an important protective barrier of our body. Macrophages are present in all organs and tissues of the body, their main functions include immune surveillance, bacterial killing, tissue remodeling and repair, and clearance of cell debris. In addition, macrophages can present antigens to T cells and facilitate inflammatory response by releasing cytokines. Macrophages are of high concern due to their crucial roles in multiple physiological processes. In recent years, new advances are emerging after great efforts have been made to explore the mechanisms of macrophage activation. Ion channel is a class of multimeric transmembrane protein that allows specific ions to go through cell membrane. The flow of ions through ion channel between inside and outside of cell membrane is required for maintaining cell morphology and intracellular signal transduction. Expressions of various ion channels in macrophages have been detected. The roles of ion channels in macrophage activation are gradually caught attention. K+ channels are the most studied channels in immune system. However, very few of published papers reviewed the studies of K+ channels on macrophages. Here, we will review the four types of K+ channels that are expressed in macrophages: voltage-gated K+ channel, calcium-activated K+ channel, inwardly rectifying K+ channel and two-pore domain K+ channel.

Direct Electrochemical Leaching Method for High-Purity Lithium Recovery from Spent Lithium Batteries.

Recovering lithium from lithium batteries (LIBs) is a promising approach for sustainable ternary lithium battery (T-LIB) development. Current lithium recovery methods from spent T-LIBs mainly concentrated on chemical leaching methods. However, chemical leaching relying on the additional acid seriously threatens the global environment and nonselective leaching also leads to low Li recovery purity. Here, we first reported a direct electro-oxidation method for lithium leaching from spent T-LIBs (Li0.8Ni0.6Co0.2Mn0.2O2); 95.02% of Li in the spent T-LIBs was leached under 2.5 V in 3 h. Meanwhile, nearly 100% Li recovery purity was also achieved, attributed to no other metal leaching and additional agents. We also clarified the relationship between lithium leaching and other metals during the electro-oxidation of spent T-LIBs. Under the optimized voltage, Ni and O maintain the electroneutrality in the structure assisting Li leaching, while Co and Mn maintain their valence states. A direct electro-oxidation Li leaching approach achieves high Li recovery purity and meanwhile overcomes the secondary pollution problem.

Acquired perforating dermatosis: A clinicopathologic study, and the features of dermoscopy and reflective confocal microscopy of 37 cases.

BACKGROUND: Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays. OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM. METHODS: Thirty-seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings. RESULTS: Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord-like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin-like or loop-like capillaries with characteristic garland arrangements. CONCLUSION: APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.

Association of organophosphate flame retardants with all-cause and cause-specific mortality among adults aged 40 years and older.

The longitudinal associations of urinary concentrations of diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP) with all-cause, cardiovascular, and cancer mortality in a population of adults aged 40 years and older are still unclear. A total of 3238 participants were included in this cohort study. Urinary BCEP levels were positively associated with all-cause mortality and cardiovascular mortality. Specifically, a logarithmic increase in BCEP concentration was related to a 26 % higher risk of all-cause mortality and a 32 % higher risk of cardiovascular mortality. No significant associations were observed for DPHP and BDCPP in relation to mortality. Doseresponse analysis confirmed the linear associations of BCEP with all-cause and cardiovascular mortality and the nonlinear inverted U-shaped association between DPHP exposure and all-cause mortality. Notably, the economic burden associated with BCEP exposure was estimated, and it was shown that concentrations in the third tertile of BCEP exposure incurred approximately 507 billion dollars of financial burden for all-cause mortality and approximately 717 billion dollars for cardiovascular mortality. These results highlight the importance of addressing exposure to BCEP and its potential health impacts on the population. More research is warranted to explore the underlying mechanisms and develop strategies for reducing exposure to this harmful chemical.

Protective Effect of Water-Soluble Acacetin Prodrug on APAP-Induced Acute Liver Injury Is Associated with Upregulation of PPARγ and Alleviation of ER Stress.

A water-soluble acacetin prodrug has been synthesized and reported by our group previously. Acetaminophen (APAP) overdose is a leading cause of acute liver injury. We found that subcutaneous injection of acacetin prodrug (5, 10, 20 mg/kg) decreased serum ALT, AST, and ALP, corrected the abnormal MDA and GSH in liver, and improved intrahepatic hemorrhage and destruction of liver structures in APAP (300 mg/kg)-treated mice. Molecular mechanism analysis revealed that the expressions of endoplasmic reticulum (ER) stress markers ATF6, CHOP, and p-PERK, apoptosis-related protein BAX, and cleaved caspase 3 were decreased by acacetin in a dose-dependent manner in vivo and in vitro. Moreover, via the acacetin-upregulated peroxisome-proliferator-activated receptor gamma (PPARγ) of HepG2 cells and liver, the suppressive effect of acacetin on ER stress and apoptosis was abolished by PPARγ inhibitor (GW9662) or PPARγ-siRNA. Molecular docking revealed that acacetin can bind to three active pockets of PPARγ, mainly by hydrogen bond. Our results provide novel evidence that acacetin prodrug exhibits significant protective effect against APAP-induced liver injury by targeting PPARγ, thereby suppressing ER stress and hepatocyte apoptosis. Acacetin prodrug is likely a promising new drug candidate for treating patients with acute liver injury induced by APAP.

A Novel Sulfonamide, Molecularly Imprinted, Upconversion Fluorescence Probe Prepared by Pickering Emulsion Polymerization and Its Adsorption and Optical Sensing Performance.

A novel, molecularly imprinted, upconversion fluorescence probe (UCNP@MIFP) for sulfonamide sensing was fabricated by Pickering emulsion polymerization using UCNP@SiO2 particles as the stabilizer and sulfamethazine/sulfamerazine as the co-templates. The synthesis conditions of the UCNP@MIFP were optimized, and the synthesized probe was characterized by scanning electron microscopy, Fourier transform infrared spectrometer, thermogravimetric analyzer, and fluorescence spectrometer. The UCNP@MIFPs showed a good adsorption capacity and a fast kinetic feature for the template. The selectivity experiment revealed that the UCNP@MIFP has a broad-spectrum molecular recognition capability. Good linear relationships were obtained over the concentration range of 1-10 ng/mL for sulfamerazine, sulfamethazine, sulfathiazole, and sulfafurazole, with low limits of detection in the range of 1.37-2.35 ng/mL. The prepared UCNP@MIFP has the potential to detect four sulfonamide residues in food and environmental water.

Characteristics of depression, anxiety, impulsivity, and aggression among various types of drug users and factors for developing severe depression: a cross-sectional study.

BACKGROUND: Mood disorder, impulsivity and aggression are common in drug users compared to healthy controls. However, no study has focused on the difference in various types of drug users. Therefore, the objective of this study was to explore the differences in depression, anxiety, impulsivity, and aggression among methamphetamine, heroin and polysubstance users and to further explore the risk factors for severe depression in the three groups. METHODS: Drug users over 18 years old who met the DSM-V diagnostic criteria for substance -related disorders were included in the study. All participants completed a general questionnaire, the Zung Self-Rating Depression Scale (SDS), the Zung Self-Rating Anxiety Scale (SAS), Barratt impulsiveness Scale Version 11 (BIS-11), and the Buss-Perry Aggression Questionnaire (BPAQ). One-way ANOVAs or Chi-square tests were used to test the differences among the groups, correlation analysis was used to test the relationship between drug use and other parameters, and multiple logistic regression was conducted to assess the risk factors for severe depression. RESULTS: A total of 1,486 participants were included, comprising 86.3% males with a mean age of 38.97 years. There was a significant difference in the percentage of severe depression and SDS scores among the three groups, but no significant difference was found in SAS, BIS-11 and BPAQ scores. Using methamphetamines, hostility and anxiety were risk factors for developing severe depression in all the participants and anxiety remained constant in the other three groups. Moreover, methamphetamine use was 2.16 and 3.35 times more likely to cause severe depression than heroin and polysubstance use, respectively. The initial age of substance use was negatively correlated with BPAQ, SAS, and SDS scores, whereas the drug use duration and addiction duration were positively correlated. CONCLUSIONS: In this study, we found that the highest prevalence of severe depression was in participants using methamphetamines and that using methamphetamines, hostility, and anxiety were risk factors for developing severe depression. This result addressed an important gap in our knowledge of the different characteristics of depression, anxiety, impulsivity and aggression in various types of substance users and provides clinicians and policy-makers with directions for intervention and preventing relapse.

Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2.

Cells express a family of three inositol hexakisphosphate kinases (IP6Ks). Although sharing the same enzymatic activity, individual IP6Ks mediate different cellular processes. Here we report that IP6K3 is enriched at the leading edge of migrating cells where it associates with dynein intermediate chain 2 (DIC2). Using immunofluorescence microscopy and total internal reflection fluorescence microscopy, we found that DIC2 and IP6K3 are recruited interdependently to the leading edge of migrating cells, where they function coordinately to enhance the turnover of focal adhesions. Deletion of IP6K3 causes defects in cell motility and neuronal dendritic growth, eventually leading to brain malformations. Our results reveal a mechanism whereby IP6K3 functions in coordination with DIC2 in a confined intracellular microenvironment to promote focal adhesion turnover.

Thermal Analyses of Nanowarming-Assisted Recovery of the Heart From Cryopreservation by Vitrification.

This study explores thermal design aspects of nanowarming-assisted recovery of the heart from indefinite cryogenic storage, where nanowarming is the volumetric heating effect of ferromagnetic nanoparticles excited by a radio frequency electromagnet field. This study uses computational means while focusing on the human heart and the rat heart models. The underlying nanoparticle loading characteristics are adapted from a recent, proof-of-concept experimental study. While uniformly distributed nanoparticles can lead to uniform rewarming, and thereby minimize adverse effects associated with ice crystallization and thermomechanical stress, the combined effects of heart anatomy and nanoparticle loading limitations present practical challenges which this study comes to address. Results of this study demonstrate that under such combined effects, nonuniform nanoparticles warming may lead to a subcritical rewarming rate in some parts of the domain, excessive heating in others, and increased exposure potential to cryoprotective agents (CPAs) toxicity. Nonetheless, the results of this study also demonstrate that computerized planning of the cryopreservation protocol and container design can help mitigate the associated adverse effects, with examples relating to adjusting the CPA and/or nanoparticle concentration, and selecting heart container geometry, and size. In conclusion, nanowarming may provide superior conditions for organ recovery from cryogenic storage under carefully selected conditions, which comes with an elevated complexity of protocol planning and optimization.

Bioapplications of Magnetic Nanowires: Barcodes, Biocomposites, Heaters.

Magnetic nanowires (MNWs) can have their moments reversed via several mechanisms that are controlled using the composition, length, diameter, and density of nanowires in arrays as-synthesized or as individual nanoparticles in assays or gels. This tailoring of magnetic reversal leads to unique properties that can be used as a signature for reading out the type of MNW for applications as nano-barcodes. When synthesized inside track-etched polycarbonate membranes, the resulting MNW-embedded membranes can be used as biocompatible bandaids for detection without contact or optical sighting. When etched out of the growth template, free-floating MNWs are internalized by cells at 37 °C such that cells and/or exosomes can be collected and detected. In applications of cryopreservation, MNWs can be suspended in cryopreservation agents (CPAs) for injection into the blood vessels of tissues and organs as they are vitrified to -200 °C. Using an alternating magnetic field, the MNWs can then be nanowarmed rapidly to prevent crystallization and uniformly to prevent cracking of specimens, for example, as grafts or transplants. This invited paper is a review of recent progress in the specific bioapplications of MNWs to barcodes, biocomposites, and nanowarmers.

A community-level study on COVID-19 transmission and policy interventions in Wuhan, China.

The specific factors and response strategies that affect COVID-19 transmission in local communities remain under-explored in the current literature due to a lack of data. Based on primary COVID-19 data collected at the community level in Wuhan, China, our study contributes a community-level investigation on COVID-19 transmission and response strategies by addressing two research questions: 1) What community factors are associated with viral transmission? and 2) What are the key mechanisms behind policy interventions towards controlling viral transmission within local communities? We conducted two sets of analyses to address these two questions-quantitative analyses of the relationship between community factors and viral transmission and qualitative analyses of policy interventions on community transmission. Our findings show that the viral spread in local communities is irrelevant to the built environment of a community and its socioeconomic position but is related to its demographic composition. Specifically, groups under the age of 18 play an important role in viral transmission. Moreover, a series of community shutdown management initiatives (e.g., group buying, delivering supplies, and self-reporting of health conditions) play an important role in curbing viral transmission at the local level that can be applied to other geographic contexts.

Effect of Metformin Therapy on Biological Properties and Prognosis of Breast Cancer Patients Complicated with Type-2 Diabetes.

Objectives: To evaluate the effect of Metformin therapy on patients of breast cancer with complications of Type-2 diabetes. Methods: Altogether 102 cases of breast cancer complicated with Type-2 diabetes admitted into Hebei General Hospital from January 2019 to December 2020 were included in the study. They were divided into two groups per whether Metformin was administered in the regimen, namely Metformin group and non-Metformin group. In the meanwhile, 106 cases of breast cancer without Type-2 diabetes admitted in the same period were selected to form a control group. Three groups were compared in terms of general data (incl. age, body mass, family history, menopause or not), clinical staging, tumor histological differentiation, molecular subtyping (Incl. Luminal A, Luminal B, ERBB2+, Basal-like) and prognosis. Results: Compared with the control group, Metformin group and non-Metformin group presented more patients with an older age and post-menopause state (P<0.05), but the latter two groups were not significantly different (P > 0.05). Patients in Metformin group and non-Metformin group had higher clinical staging and histological differentiation and more cases of Basal-like subtype than those in the control group (P < 0.05), without significant difference between those two groups (P > 0.05). More cases of local relapse, lymphatic and distant metastasis were seen in Metformin and non-Metformin groups, but the differences were not significant (P > 0.05). Both groups had lower 5-year survival rates than the control group (P < 0.05). Metformin group had a higher overall survival rate as well as a survival rate free of other lethal reasons than the non-Metformin group (P < 0.05) but was not significantly different from the control group in the survival rate free of other lethal reasons (P > 0.05). Conclusions: Type-2 diabetes remains one of the risk factors affecting breast cancer development, progress and prognosis, which could lower the 5-year overall survival rate among breast cancer patients. This is especially evident among menopaused women. Metformin therapy may improve the prognosis of patients of breast cancer complicated with Type-2 diabetes.

Expressions of IGF-1R and Ki-67 in breast cancer patients with diabetes mellitus and an analysis of biological characteristics.

OBJECTIVES: There is a cross-link of insulin and insulin-like growth factor-1 (IGF-1) with each other's receptors. The present study was carried out to explore the relationship of Type-2 diabetes mellitus (T2DM) with the occurrence and development of breast cancer by analyzing the expression of IGF-1R and Ki-67, as well as the biological characteristics in breast cancer patients with and without diabetes mellitus. METHODS: A total of 102 cases of breast cancer patients with T2DM admitted in Hebei General Hospital from January 2019 to December 2020 were selected and grouped in T2DM group. While the control group included 106 cases of breast cancer patients without diabetes mellitus in the same period. Further comparison was conducted focusing on the general data, clinical stage, tumor histological grade, molecular classification and prognosis, and the expressions of IGF-1R and Ki-67 in breast cancer tissue between groups. RESULTS: Compared with control group, patients in T2DM group were elderly and accounted for a larger proportion of post-menopause (p<0.05), yet with no significant difference in body mass and family history (p>0.05). Compared with control group, T2DM group had advanced clinical stage, higher histological grade, and more common molecular type, with statistical differences between groups (p<0.05). Furthermore, there were higher proportions of local recurrence, lymph node metastasis and distant metastasis in T2DM group than those in control group, yet with no statistical significance (p>0.05). While statistical difference was found in the comparison of the 5-year survival rate, which was lower in T2DM group than that in control group (p<0.05). In addition, compared with control group, there were significant increase in both the expressions of IGF-1R and Ki-67 in T2DM group (p<0.05). CONCLUSIONS: T2DM may be one of the risk factors affecting the occurrence, development and prognosis of breast cancer, which may decrease the 5-year survival of breast cancer patients. Besides, high expressions of IGF-1R and Ki-67 may be the key factors for poor prognosis of breast cancer patients with diabetes mellitus.