High-Temporal-Resolution In Situ Sensor for Oceanic CO2 Isotope Measurement Enabling Multidimensional Isotope Tracing Analysis (R13C, R18O, and R17O) via Laser Absorption Spectroscopy.

Combined in situ analysis of oceanic CO2 concentrations and diverse C and O isotope characteristics can offer a unique perspective with multiple isotopic tracing dimensions for identifying marine biogeochemical processes. Applying this strategy in marine environments is urgently required, yet it faces inherent challenges in terms of existing analytical methods and instruments, e.g., a lack of in situ sensors, limited detectable isotope variety, and low-temporal-resolution data. Here, we report an underwater in situ dissolved CO2 isotope sensor based on mid-infrared tunable diode laser absorption spectroscopy (MIR-TDLAS) and membrane extraction technology. Through the proposed targeted strategies, the sensor is capable of providing high-temporal-resolution in situ measurement of all monosubstituted isotopes of dissolved CO2 (16O13C16O, 18O12C16O, and 17O12C16O) at marine background concentrations. The sensor is demonstrated to provide comparable precision to that of isotope ratio mass spectrometry. At 400 ppmv, the precision for R13C, R18O, and R17O could achieve 0.084, 0.042, and 0.013‰, respectively, for a 1 s integration time. By enabling a high-frequency in situ analysis in fixed-point time-series field deployment, a 17O anomaly with strong regularity is observed, which is not obvious in 18O and 13C, and therefore, the superiority of the proposed multidimensional in situ isotope tracing strategy is demonstrated. The developed sensor has great potential to open up new prospects for advancing marine carbon research.

The inhibitory effect of Gremlin-2 on adipogenesis suppresses breast cancer cell growth and metastasis.

BACKGROUND: Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet. METHODS: Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression. RESULTS: Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2. CONCLUSIONS: Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression.

Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of ß-catenin.

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/ß-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 µM) dose-dependently inhibited TOPFlash reporter activity and protein expression of ß-catenin, but not mRNA level of ß-catenin. Furthermore, celastrol accelerated the degradation of ß-catenin by promoting the formation of the ß-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/ß-catenin signaling by promoting the degradation of ß-catenin, consequently inhibiting the growth of VS.

Gremlin-1 activates Akt/STAT3 signaling, which increases the glycolysis rate in breast cancer cells.

Gremlin-1 (GREM1), one of the antagonists of bone morphogenetic proteins (BMPs), has recently been reported to be overexpressed in a variety of cancers including breast cancer. GREM1 is involved in tumor promotion, but little is known about its role in the glycolysis of cancer cells. In this study, we investigated the role of GREM1 in glycolysis of breast cancer cells and its underlying molecular mechanisms. We first observed that glucose uptake and lactate production were increased in GREM1-overexpressing breast cancer cells. GREM1 increased the expression of hexokinase-2 (HK2), which catalyzes the phosphorylation of glucose, the first step in glycolysis. In addition, GREM1 activated STAT3 transcription factor through the ROS-Akt signaling pathway. The ROS-Akt-STAT3 axis activated by GREM1 was involved in promoting glucose uptake by increasing the expression of HK2 in breast cancer cells. Therefore, our study suggested a new mechanism by which GREM1 is involved in breast cancer promotion by increasing glycolysis in breast cancer cells.

Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway.

Gremlin-1 (GREM1), one of the bone morphogenetic protein (BMP) antagonists, can directly bind to BMPs. GREM1 is involved in organogenesis, tissue differentiation, and organ fibrosis. Recently, numerous studies have reported the oncogenic role of GREM1 in cancer. However, the role of GREM1 in metastasis of breast cancer cells and its underlying mechanisms remain poorly understood. The role of GREM1 in breast cancer progression was assessed by measuring growth, migration, and invasion of breast cancer cells. An orthotopic breast cancer mouse model was used to investigate the role of GREM1 in lung metastasis of breast cancer cells. GREM1 knockdown suppressed the proliferation of breast cancer cells, while its overexpression increased their growth, migration, and invasion. Cells with Grem1-knockdown showed much lower tumor growth rates and lung metastasis than control cells. GREM1 enhanced the expression of matrix metalloproteinase 13 (MMP13). A positive correlation between GREM1 and MMP13 expression was observed in breast cancer patients. GREM1 activated signal transducer and activator of transcription 3 (STAT3) transcription factor involved in the expression of MMP13. Our study suggests that GREM1 can promote lung metastasis of breast cancer cells through the STAT3-MMP13 pathway. In addition, GREM1 might be a promising therapeutic target for breast cancer metastasis.

Dietary pattern and health-related quality of life among breast cancer survivors.

BACKGROUND: There is limited evidence for the association between dietary pattern and quality of life among breast cancer survivors. We examined the association between dietary patterns and health-related quality of life (HRQoL) among Korean breast cancer survivors. METHODS: Our study included a total of 232 women, aged 21 to 79 years, who had been diagnosed with stage I to III breast cancer and who underwent breast cancer surgery at least 6 months prior to our baseline evaluation. We assessed HRQoL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23). We conducted a factor analysis to identify the major dietary patterns and used a generalized linear model to obtain the least squares mean (LS mean) and 95% confidence interval (CI) for HRQoL according to the dietary pattern scores. RESULTS: We identified 2 major dietary patterns: the Healthy dietary pattern and the Western dietary pattern. We found that breast cancer survivors who had higher Healthy dietary pattern scores tended to have lower dyspnea scores but higher insomnia scores, compared to breast cancer survivors with lower Healthy dietary pattern scores. For dyspnea, the LS mean (95% CI) was 8.86 (5.05-15.52) in the bottom quartile and 2.87 (1.62-5.08) in the top quartile (p for trend = 0.005). This association was limited to survivors with stage I for dyspnea or survivors with stage II or III for insomnia. CONCLUSIONS: Healthy dietary patterns were associated with better scores for dyspnea but worse scores for insomnia among breast cancer survivors. Other components of EORTC QLQ did not vary by dietary patterns overall, but they warrant further investigation for subgroups of breast cancer survivors.

Dietary diversity and nutritional adequacy among married Filipino immigrant women: The Filipino Women's Diet and Health Study (FiLWHEL).

BACKGROUND: Migration has an influence on health behavior and food intake. Dietary variety is a key component to high-quality diets because a single food item does not contain a variety of nutrients and may not reflect nutritional adequacy. We aimed to compare the dietary diversity scores (DDS), food variety scores (FVS), and nutrient adequacy levels of married Filipino immigrant women in Korea to those of Korean women. METHODS: We matched the data of 474 participants aged 20-57 years from the Filipino Women's Diet and Health Study (FiLWHEL) by age category with those of married Korean women randomly selected from the Korea National Health and Nutrition Examination Survey (KNHANES). Dietary information in FiLWHEL and KNHANES were assessed through the 24-hour recall method. We calculated the DDS by summing the number of eleven food groups consumed (DDS 10 g if they consumed at least 10 g/day; DDS all if they consumed any amount) and the FVS by counting the number of food items consumed. For nutrient adequacy, we calculated the probability of adequacy (PA) and intake below the estimated average requirement (EAR). RESULTS: Filipino women had a lower DDS and FVS in comparison to Korean women. The means (±SDs) of DDS 10 g, DDS all, and FVS for Filipino women versus Korean women were 6.0 (±1.6) versus 6.8 (±1.5) (p < 0.001), 6.7 (±1.7) versus 7.9 (±1.4) (p < 0.001) and 9.2 (±3.3) versus 14.7 (±4.9) (p < 0.001), respectively. When we compared each food group, the intakes of fish, other seafood, legumes/seeds/nuts, eggs, vegetables, and fruits were lower for Filipino women than for Korean women. The mean probability of adequacy (MPA) of nutrient intake of the nine selected nutrients was lower for Filipino women in comparison to Korean women. The mean (±SD) was 0.55 (±0.28) versus 0.66 (±0.26), respectively. CONCLUSIONS: Our findings showed that married Filipino immigrant women in Korea had lower dietary variety scores in comparison to Korean women. This was reflected in their nutritional adequacy. Nutrition education focusing on the promotion of eating a variety of foods may be needed for Filipino immigrant women in Korea.

One-Step Microfluidic Fabrication of Polyelectrolyte Microcapsules in Aqueous Conditions for Protein Release.

We report a microfluidic approach for one-step fabrication of polyelectrolyte microcapsules in aqueous conditions. Using two immiscible aqueous polymer solutions, we generate transient water-in-water-in-water double emulsion droplets and use them as templates to fabricate polyelectrolyte microcapsules. The capsule shell is formed by the complexation of oppositely charged polyelectrolytes at the immiscible interface. We find that attractive electrostatic interactions can significantly prolong the release of charged molecules. Moreover, we demonstrate the application of these microcapsules in encapsulation and release of proteins without impairing their biological activities. Our platform should benefit a wide range of applications that require encapsulation and sustained release of molecules in aqueous environments.

Preparation of Au Nanoparticles Immobilized Cross-Linked Poly(4-vinylpyridine) Nanofibers and Their Catalytic Application for the Reduction of 4-Nitrophenol.

Catalytic nanofibers are prepared by the immobilization of Au nanoparticles (AuNPs) onto the surface of cross-linked electrospun poly(4-vinylpyridine) (P4VP) nanofibers. The crosslinking of the P4VP nanofibers by 1,4-diiodobutane via quaternization reaction greatly enhances the stability of the nanofibers against the solvent dissolution, which can then be used as promising platform for the immobilization of catalytic metal nanoparticles. The AuNPs immobilized cross-linked P4VP nanofibers have shown a good catalytic activity for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP).

Research and application of knowledge resources network for product innovation.

In order to enhance the capabilities of knowledge service in product innovation design service platform, a method of acquiring knowledge resources supporting for product innovation from the Internet and providing knowledge active push is proposed. Through knowledge modeling for product innovation based on ontology, the integrated architecture of knowledge resources network is put forward. The technology for the acquisition of network knowledge resources based on focused crawler and web services is studied. Knowledge active push is provided for users by user behavior analysis and knowledge evaluation in order to improve users' enthusiasm for participation in platform. Finally, an application example is illustrated to prove the effectiveness of the method.

Mechanical behavior of poly(methyl methacrylate)-based ionogels.

Ionogels are formed when a cross-linked polymer network absorbs an ionic liquid. Ionogels are ionic conductors and, as such, are being considered for use in stretchable electronics and artificial muscles or nerves. The use of ionogels in these applications is limited in part by their mechanical behavior. Here we present an ionogel prepared by swelling covalently cross-linked poly(methyl methacrylate) in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide. The resulting ionogel is compliant, stretchable, and relatively tough. We demonstrate that the swelling ratio, elastic modulus, stretchability, and fracture energy of the ionogel depend sensitively on the cross-link density of the polymer network. The behavior of the ionogel is well captured by the model of the ideal elastomeric gel combined with the Flory-Huggins model for the energy of mixing.

The empirical effect of agricultural social services on pesticide inputs.

Agricultural social services (ASS) play an important role in improving the efficiency of agricultural operations, reducing agricultural production costs, and promoting sustainable agricultural development. Using data from the 2020 China Rural Revitalization Survey, this study analyzes the impact of ASS on reducing pesticide inputs. The results show: (1) ASS play a significantly positive role in reducing pesticide inputs. (2) Heterogeneity analyses show that ASS' role in reducing pesticide inputs is stronger for farming households with small farms, which participate in cooperatives, and do not have members involved in non-farm employment than that for farming households with large farms, which do not participate in cooperatives, and have members involved in non-farm employment. (3) Mechanism analysis shows that ASS' green perception and demonstration-led effects contribute to reducing pesticide inputs by 148.6% and 36.8%, respectively, at the 1% level. Finally, this study proposes relevant policy recommendations for promoting ASS, promoting the continuous operation of farmland, and encouraging farmers to participate in ASS.

Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

Research on the impact of internet use on fertilizer and pesticide inputs: Empirical evidence from China.

Fertilizers and pesticides are important agricultural production materials. Excessive use of fertilizers and pesticides can cause negative impacts such as decline in the quality of farm products and damage to the ecological environment. Increasing the efficiency of fertilizers and pesticides is an important step to accelerate the green transformation of agriculture. Using data from the 2015 China Household Finance Survey, this paper analyzes the impacts of Internet use on fertilizers and pesticides by farmers, and the mechanism behind the action with the help of the propensity score matching method and the instrumental variable method. The findings are: (1) Farmers who use the Internet have greater inputs of fertilizers and pesticides compared to farmers who do not use the Internet. (2) Farmers who do not use the Internet would have their inputs of fertilizers and pesticides increased by 21.9% and 47.7%, respectively, if they had used the Internet under the counterfactual hypothesis. (3) In the heterogeneity analysis, Internet use plays a positive and significant role in the inputs of fertilizer and pesticide in the eastern part of China, and Internet use has greater impact on pesticide inputs than on fertilizer in central and western regions. (4) Internet use has a positive and significant effect on fertilizer and pesticide inputs in both lower scale and higher scale operations, and a positive but not significant effect in moderate-scale operations.

Diesel exhaust particle exposure accelerates oxidative DNA damage and cytotoxicity in normal human bronchial epithelial cells through PD-L1.

Diesel exhaust particles (DEPs) are a major cause of cancer progression as well as a variety of acute and chronic diseases. It is well-known that programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can induce immune escape in tumor cells. However, the function of PD-L1 in bronchial epithelial cells or how PD-L1 relates to cellular oxidation under DEPs-mediated oxidative stress is not well known. In this study, we investigated how PD-L1 affected DEPs-induced oxidative stress and cytotoxicity in human bronchial epithelial (HBE) cells, Beas-2B. DEPs not only induced intracellular reactive oxygen species (ROS) production, but also increased PD-L1 expression in HBE cells. Beas-2B cells overexpressing PD-L1 showed higher levels of ROS production, DNA damage, and apoptosis after DEPs treatment compared to control cells. In particular, the expression of an antioxidant enzyme heme-oxygenase-1 (HO-1) and nuclear translocation and transcriptional activity of Nrf2, a major regulator of HO-1, were lower in Beas-2B overexpressing PD-L1 cells than in control cells. DEPs-induced ROS generation, DNA damage and apoptosis in Beas-2B cells overexpressing PD-L1 were significantly restored by overexpressing HO-1. Collectively, our results suggest that DEPs can increase the expression of PD-L1 in HBE cells and that overexpressing PD-L1 might eventually promote DEPs-induced oxidative DNA damage and apoptosis.

PAEs Derivatives' Design for Insulation: Integrated In-Silico Methods, Functional Assessment and Environmentally Friendly Molecular Modification.

As a common substance in production and life, phthalic acid esters (PAEs), the main component of plastics, have brought more and more serious problems to the environment. This study normalized the insulation, toxicity, and bioconcentration data of 13 PAEs to eliminate the dimensional coefficients of each index, and then used the comprehensive index method to calculate the comprehensive effect value of PAEs with three properties. The comprehensive effect value was used as the data source to construct the 3D-QSAR model of PAE molecular comprehensive effect. The DAP was selected as the target molecule, the distribution of each force field in the three-dimensional equipotential map was analyzed, and 30 molecular modification schemes were created. The constructed single-effect models of insulation, toxicity, and bioconcentration of PAEs and the scoring function module of DS software were used to evaluate the stability and environmental friendliness of PAE derivative molecules. Four PAE derivatives were screened for increased comprehensive effects, enhanced insulation, and reduced toxicity and bioconcentration. By calculating the binding energy of the target molecule and the derivative molecule with the degrading enzyme under different applied electric fields, it was found that the binding energy of DAP-1-NO2-2-CH2C6H5 decreases more than DAP does when there is an applied electric field, indicating that the degradation ability of degrading enzymes on PAE derivative molecules is reduced, which indirectly proves that the insulation is enhanced. The innovation of this paper lies in the insulation, toxicity, and bioenrichment data of PAEs being processed by mathematical method for the first time, and PAEs with high insulation, low toxicity, and low bioconcentration were designed by building a comprehensive model.

Control Strategies of Plastic Biodegradation through Adjusting Additives Ratios Using In Silico Approaches Associated with Proportional Factorial Experimental Design.

Plastics, as a polymer material, have long been a source of environmental concern. This paper uses polystyrene plastics as the research object, and the relative contribution of each component of plastic additives to plastic degradation is screened using the molecular dynamics method. The factorial experimental design method is combined with molecular dynamics simulation to adjust the additive composition scheme, analyze the mechanism of interaction between the additive components, and select the plastic additive combination that is most readily absorbed and degraded by microorganisms. Seven different types of plastic additives, including plasticizers, antioxidants, light and heat stabilizers, flame retardants, lubricants, and fillers, are chosen as external stimuli affecting the biodegradability of plastics. Using molecular dynamics simulation technology, it is demonstrated that plastic additives can promote the biodegradability of plastics. The factorial experimental design analysis revealed that all plastic additives can promote plastic biodegradation and plasticizer is the most favorable factor affecting plastic degradation, that hydrophobicity interactions are the primary reason for enhancing plastic degradation, and that screening No. 116-45 (plasticizer A, light stabilizer C, flame retardant E) is the most advantageous combination of biodegradable plastic additives. The plastic biodegradation effect regulation scheme proposed in this study is based on optimizing the proportion of additive components. To continue research on aquatic biodegradable plastics, the optimal combination of plastic components that can be absorbed and degraded by microorganisms is recommended.

Retrospective Study of Aging and Sex-Specific Risk Factors of COVID-19 with Hypertension in China.

Background: Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients. Methods: We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups. Results: Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0-57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23-1.05; p = 0.043) and triglycerides (OR: 1.173, 95% CI: 0.049-1.617; p = 0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein. Conclusions: Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.

Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.

Sauchinone, a lignan isolated from Saururus chinenesis, is known to exhibit anti-inflammatory and anti-oxidant effects. Recently, sauchinone has been reported to inhibit the growth of various cancer cells, but its effects on breast cancer cells remain poorly understood. In the present study, we investigated the effects of sauchinone on the growth of breast cancer cells along with the underlying molecular mechanisms. Our results show that sauchinone treatment markedly inhibited the proliferation, migration, and invasion of breast cancer cells. Sauchinone reduced the phosphorylation of Akt, ERK, and CREB increased by transforming growth factor-ß (TGF-ß). In particular, sauchinone treatment suppressed the expression of matrix metalloproteinase (MMP)-13 (MMP13) by regulating the Akt-CREB signaling pathway. Sauchinone was less effective in inhibiting cell migration in Mmp13-knockdown cells than in control cells, suggesting that MMP13 may be a novel target for sauchinone. Our study suggests that sauchinone inhibits the growth of breast cancer cells by attenuating the Akt-CREB-MMP13 pathway. In addition, the targeted inhibition of MMP13 by sauchinone represents a promising approach for the treatment of breast cancer.

Risk Factors in Patients with Diabetes Hospitalized for COVID-19: Findings from a Multicenter Retrospective Study.

METHODS: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors. RESULTS: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study. CONCLUSION: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.