SEC-HPLC analysis of column load and flow-through provides critical understanding of low Protein A step yield.

For a certain number of mAbs, bispecific antibodies (bsAbs) and Fc-fusion proteins that we worked on, the Protein A capture step experienced low yield (i.e., ∼80%). A previous case study suggested that non-binding aggregate formed in cell culture was the root cause of low Protein A step yield. In the current work, we selected five projects with the low Protein A yield issue to further illustrate this phenomenon. In all cases, existence of non-binding aggregates was confirmed by size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC) analysis of Protein A load and flow-through. In addition, we demonstrated that aggregates failed to bind to Protein A resin mainly due to their large sizes, which prevented them from entering the resin beads. As the data suggested, SEC-HPLC analysis of Protein A load and flow-through, although not a standard procedure, can provide information that is critical for understanding the unexpected performance of Protein A chromatography in cases like those being presented here. Thus, SEC-HPLC analysis of Protein A load and flow-through is highly recommended for antibodies/Fc-fusions suffering from low Protein A yield.

A Cu-Based Metal-Organic Framework Cu-Cip with Cuproptosis for Cancer Therapy and Inhibition of Cancer Cell Migration.

Microflora within cancer cells plays a pivotal role in promoting metastasis of cancer. However, contemporary anticancer research often overlooks the potential benefits of combining anticancer and antibacterial agents. Consequently, a metal-organic framework Cu-Cip with cuproptosis and antibacterial properties was synthesized for cancer therapy. To enhance the anticancer effect of the material, Mn2+ was loaded into Cu-Cip, yielding Mn@Cu-Cip. The fabricated material was characterized using single-crystal X-ray diffraction, PXRD, and FT-IR. By interacting with overexpressed H2O2 to produce ROS and accumulating Cu ions in cancer cells, MOFs exhibited excellent anticancer performance. Moreover, the material displayed the function of damaging Staphylococcus aureus and Escherichia coli, revealing the admirable antibacterial properties of the material. In addition, the antibacterial ability could inhibit tumor cell migration. The Cu-based MOF revealed promising applications in the field of tumor treatment.

Multidrug-resistant organisms may be associated with bed allocation and utilization efficiency in healthcare institutions, based on national monitoring data from China (2014-2020).

Analyzing the influence of the bed allocation and utilization efficiency in healthcare institutions on the isolation proportion of Multidrug-resistant organisms (MDROs) to provide data to support prevention and control of MDROs. In this study, the provincial panel data from 2014 to 2020 in China on health resource indicators, including the number of beds per 1,000 population, hospital bed utilization rate, and average hospital stay from 2014 to 2020 in China were used to analyze the relationship between bed allocation or utilization efficiency and MDROs by the panel data quantile regression model. It was shown that the number of beds per 1,000 population had a negative effect on the isolation proportion of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, methicillin-resistant coagulase-negative Staphylococcus, and cefotaxime or ceftriaxone resistant Escherichia coli (regression coefficient < 0, P < 0.05). The utilization rate of hospital bed had a positive effect on the isolation proportion of methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, cefotaxime or ceftriaxone resistant Escherichia coli, carbapenem-resistant Escherichia coli, cefotaxime or ceftriaxone resistant Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (regression coefficient > 0, P < 0.05). The average hospital stay had a positive effect on the isolation proportion for several antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, cefotaxime or ceftriaxone resistant Escherichia coli, carbapenem-resistant Escherichia coli, quinolone-resistant Escherichia coli, cefotaxime or ceftriaxone resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (regression coefficient > 0, P < 0.05). Bed allocation and utilization efficiency in healthcare institutions may affect the isolation proportion of MDROs in varying degrees.

Design and implementation of a dual aspheric integrated shaping element for a high-power fiber laser.

A dual aspheric integrated beam shaper suitable for a high-power laser situation has been designed and realized. The model for this lens was derived theoretically and the performance was evaluated using a detailed simulation. The ultrasonic vibration assisted cutting and the high-precision grinding and polishing technology were used for the processing. The surface accuracy was less than 200 nm measured with a profiler, and the roughness was smaller than 20 nm with the help of the white light interferometer. Shaping experiments were carried out, which verified that the Gaussian beam has uniform intensity distribution with a uniformity of 85.13% in the near field and converges to a point in the far field, which is exactly as expected. It thus provides an actual selection for high-power laser shaping.

Construction of Core-Shell MOF CSMnP with Enzyme-Like Activity for Chemotherapy and Chemodynamic Therapy.

Materials with enzyme-like activity have received a lot of attention in the field of tumor catalytic therapy. Here, biocompatible core-shell MOF CSMnP with two valence states of Mn ion, which could process chemodynamic therapy (CDT), was designed and synthesized. Besides, it could also promote a series of catalytic processes in the tumor microenvironment (TME). CSMnP catalyzed endogenous hydrogen peroxide (H2O2) to oxygen (O2) via catalase-like activity and then combined with the outer layer Mn(II)-PBC to convert O2 into superoxide radicals (•O2-), exhibiting oxidase-like activity. Besides, intracellular glutathione (GSH) could be effectively consumed through the glutathione oxidase-like activity of Mn3+. The occurrence of the cascade reactions effectively amplified the enzymatic production to enhance CDT. Furthermore, the therapeutic effect of CSMnP was improved through the loading of cationic drug DOX. The loading capacity was 11.10 wt %, which was 2.2 times that of Mn(III)-PBC (4.95 wt %), and the release of DOX showed a characteristic response. Therefore, the core-shell MOF with enzyme-like activity had a potential application for tumor combination therapy.

Dementia increases the risk of death in stroke patients: A retrospective cohort-based risk score model study.

BACKGROUND: The relationship between dementia and the mortality of stroke is a significant concern for patients and careers. However, there are few research about it in China and a lack of reliable data on the risk of dementia. We aim to analyze and compare the risk of death in stroke patients with and without dementia. Further investigation into the predictive value of dementia for stroke death. METHODS: All patients with stroke who were identified among residents of Ningxia, between January 1, 2014 to December 31, 2021, set death or May 22, 2022 as the observation endpoint. All patients were screened by 1:4 propensity score matching (PSM). The association between dementia and all-cause mortality was evaluated using Cox regression with survival time. Evaluation of the predictive value of dementia using decision curve analysis (DCA) and clinical impact curve (CIC) curves. RESULT: Mortality of stroke with dementia is 45.4% and without dementia is 13.8%, further calculated one-year mortality is higher in the patients with dementia than without dementia (17.3%vs. 5.4%, p < 0.001). Stroke patients with dementia had a 3.74 times higher risk of death (95% CI = 3.29,4.26) and had a shorter survival time than those without dementia. Dementia was an independent predictor of death in all models (hazard ratio [HR]=3.77,95%CI: 3.31-4.30, p < 0.001). DCA and CIC curves indicated that dementia has a high value in predicting the risk of death in stroke patients. CONCLUSION: Dementia is an independent risk factor for death and reduces survival time in stroke patients.

Increased Incidence and Risk Factors of Infections by Extended-Spectrum ß-Lactamase-Producing Enterobacterales During the COVID-19 Pandemic: A Retrospective Case-Control Study.

Purpose: To investigate changes in the incidence of infections by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) and analyzed whether there was an association between endogenous changes in the organism due to COVID-19 infection and the infections by ESBL-E. Patients and Methods: The study was a single-center retrospective case-control design. A total of 107 patients infected by ESBL-E during the COVID-19 pandemic were selected as the case group, while 214 uninfected patients selected by 1:2 propensity score matching (PSM) acted as the control group. Univariate analysis, LASSO logistic regression, and multivariate logistic regression were used to determine the risk factors for ESBL-E infection. An interrupted time series was used to analyze the changes in the incidence of ESBL-E infections in hospitalized patients during the COVID-19 pandemic. Results: The incidence of infection with ESBL-E showed a significant increase during COVID-19 (3.42 vs 4.92 per 1000 patients, p = 0.003). The incidence of ESBL-E infections increased at an average rate of 0.45 per 1000 patients per week compared to the pre-pandemic period (p = 0.022). Multivariate logistic regression analysis showed that a length of hospitalization ≥ 15 days (OR: 2.98 (1.07-8.28), chronic kidney disease (OR: 4.25 (1.32-13.70), white blood cell (WBC) > 9.5×10^9/L (OR: 3.04 (1.54-6.01), use of hormonal drugs (OR: 2.38 (1.04-5.43), antibacterial drug use 1 type (OR: 5.38 (2.04-14.21), antibacterial drug use 2 types (OR: 23.05 (6.71-79.25) and antibacterial drug use ≥ 3 types (OR: 88.35 (8.55-912.63) were independent risk factors for infection with ESBL-E, while chronic obstructive pulmonary disease (COPD) was a protective factor (OR: 0.14 (0.03-0.66). COVID-19 was not an independent risk factor for infection by ESBL-E. Conclusion: During the COVID-19 pandemic, the incidence of infections by ESBL-E increased significantly. Increased exposure to traditional risk factors were the main reasons, however, COVID-19 was not an independent risk factor for ESBL-E infection.

Silencing of TRAF5 enhances necroptosis in hepatocellular carcinoma by inhibiting LTBR-mediated NF-κB signaling.

Background: Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis and high mortality. This study aimed to explore the oncogenic mechanisms of TRAF5 in HCC and provide a novel therapeutic strategy for HCC. Methods: Human HCC cell lines (HepG2, HuH7, SMMC-LM3, and Hep3B), normal adult liver epithelial cells (THLE-2), and human embryonic kidney cells (HEK293T) were utilized. Cell transfection was performed for functional investigation. qRT-PCR and western blotting were used to detect mRNA expression of TRAF5, LTBR, and NF-κB and protein expression of TRAF5, p-RIP1(S166)/RIP1, p-MLKL(S345)/MLKL, LTBR, and p-NF-κB/NF-κB. Cell viability, proliferation, migration, and invasion were evaluated using CCK-8, colony formation, wound healing, and Transwell assays. Cell survival, necrosis, and apoptosis were assessed using flow cytometry and Hoechst 33342/PI double staining. Co-immunoprecipitation and immunofluorescence were performed to determine the interaction between TRAF5 and LTBR. A xenograft model was established to validate the role of TRAF5 in HCC. Results: TRAF5 knockdown inhibited HCC cell viability, colony formation, migration, invasion, and survival but enhanced necroptosis. Additionally, TRAF5 is correlated with LTBR and TRAF5 silencing down-regulated LTBR in HCC cells. LTBR knockdown inhibited HCC cell viability, while LTBR overexpression eliminated the effects of TRAF5 deficiency on inhibiting HCC cell proliferation, migration, invasion, and survival. LTBR overexpression abolished the promotive function of TRAF5 knockdown on cell necroptosis. LTBR overexpression undid the suppressive effect of TRAF5 knockdown on NF-κB signaling in HCC cells. Moreover, TRAF5 knockdown suppressed xenograft tumor growth, inhibited cell proliferation, and promoted tumor cell apoptosis. Conclusions: TRAF5 deficiency facilitates necroptosis in HCC by suppressing LTBR-mediated NF-κB signaling.

A multifunctional black phosphorus nanosheet-based immunomagnetic bio-interface for heterogeneous circulating tumor cell capture and simultaneous self-identification in gastric cancer patients.

A single epithelial cell adhesion molecule (EpCAM) for circulating tumor cell (CTCs) isolation has been proved to be low in efficiency as it fails to recognize EpCAM-negative CTCs. Meanwhile, the current immunocytochemical (ICC) identification strategy for the captured cells is tedious and time-consuming. To address these issues, we designed a dual-labeled fluorescent immunomagnetic nanoprobe (BP-Fe3O4-AuNR/Apt), by loading magnetic Fe3O4 nanoparticles and gold nanorods (AuNRs) onto black phosphorus (BP) nanosheets and then linking them with Cy3-labeled EpCAM and Texas red-labeled tyrosine protein kinase 7 (PTK7) aptamers, which created a high-performance bio-interface for efficient, heterogeneous CTC capture and rapid self-identification with high accuracy. As few as 5 CTCs could be captured from 1.0 mL PBS, mixed cell solution and lysed blood. What's more, the presence of BP and AuNRs on this capturing interface also allowed us to preliminarily investigate the potential photothermal therapeutic effect of the probe toward CTC elimination. The applicability of the probe was further demonstrated in gastric cancer patients. By detecting the number of CTCs in the blood of gastric cancer patients, the correlations between the CTC number and the disease stage, as well as distant metastasis were systematically explored.

A liposome-based aptasensor integrated with competitive reaction enabling portable and electrochemical detection of Aß oligomer.

Aggregation of ß-amyloid (Aß) were considered as a typical pathological feature of Alzheimer's disease (AD). Extensive studies have verified that soluble Aß oligomers (AßO) were more toxic to neurons than plaques. Herein, in this work, a glucose entrapped liposome-based portable aptasensor was fabricated for recognizing and interacting with AßO by specific aptamer on liposome (G-Lip-Apt). Then, a single strand DNA, designed to be partially complementary to AßO aptamer, was modified on amino-functionalized Fe3O4@SiO2 to obtain a magnetic nanocomposite (Fe3O4@SiO2/NH2-DNA). In the presence of AßO, the specific recognition between AßO and its aptamer on G-Lip-Apt made AßO bounded with G-Lip-Apt. With subsequent introduction of Fe3O4@SiO2/NH2-DNA, the unreacted G-Lip-Apt was further linked with Fe3O4@SiO2/NH2-DNA by double stranded complementary pairing interaction. Along with the addition of TritonX-100 into the formed G-Lip-Apt/Fe3O4@SiO2/NH2-DNA complex, the encapsulated glucose was released from liposome and then measured by a personal glucose meter (PGM). Good linear correlation was acquired over concentration of 5.0-1000 nM and the limit of detection (LOD) was calculated to be 2.27 nM for AßO. The developed portable electrochemical strategy integrated magnetic separation, competitive reaction and point of care test (POCT) to achieve high sensitivity, selectivity and accuracy, therefore enabled it successfully applied to the analysis of AßO in the hippocampus and cortex of APP/PS1 transgenic AD mice.

Glucometer Readout for Portable Detection of Heterogeneous Circulating Tumor Cells in Lung Cancer Captured on a Dual Aptamer Functionalized Wrinkled Cellulose Hydrogel Interface.

The rarity of circulating tumor cells (CTCs) poses a great challenge to their clinical application as reliable "liquid biopsy" markers for cancer diagnosis. Meanwhile, the epithelial-mesenchymal transition (EMT) led to a reduced efficiency in capturing cells with lost or downregulated epithelial cell adhesion molecule (EpCAM) expressions. In this study, we proposed an integrated, highly efficient strategy for heterogeneous CTC capture and portable detection from the blood of non-small-cell lung cancer (NSCLC) patients. First, the cellulose wrinkled hydrogel with excellent biocompatibility and high specific area was employed as the biointerface to capture heterogeneous CTCs with an improved capture efficiency in virtue of dual targeting against epithelial and mesenchymal ones. Meanwhile, the strategy of glucometer readout was introduced for the quantification of captured CTCs on the same hydrogel interface by a detection probe, Au-G-MSN-Apt, which was fabricated via entrapping glucose into the amino group functionalized mesoporous silica nanoparticle (MSN) framework sealed by l-cysteine modified gold nanoparticles (AuNPs) and then linked with dual aptamers of EpCAM and Vimentin. The number of captured CTCs on the hydrogel could be reflected according to the portable glucose meter (PGM) readings. Moreover, it was found that the captured cells maintained a higher viability on the hydrogel and could be in situ recultured without releasing from the substrate. Finally, this integrated strategy was successfully applied to inspect the correlations between the number of heterogeneous CTCs in the blood of NSCLC patients with disease stage and whether there was distant metastasis.

Exploring the Target and Mechanism of Radix Paeoniae Alba on Sjogren's Syndrome.

BACKGROUND: Radix Paeoniae Alba is a traditional Chinese herbal medicine. It can accelerate salivary secretion and alleviate the dry mouth of patients with Sjogren's syndrome (SS). Although it is widely used in clinical treatment, its target and mechanism remain unclear. OBJECTIVE: This study aims to analyze the main components of Radix Paeoniae Alba, explore the target genes, and propose the possible mechanism for Radix Paeoniae Alba's acceleration of salivary secretion. METHODS: The main active components and potential targets of Radix Paeoniae Alba were searched through the TCMSP database. Efforts were made to search for the related genes of Sjogren's syndrome in OMIM and GeneCards databases. Cytoscape v3.8.0 software was used to link target genes of active components and key genes of the disease. The software Autodock vina1.1.2. was adopted to simulate the interaction between active components and target genes. Human submandibular gland (HSG) cells were used in vitro experiments to verify the results of our analysis. RESULTS: ß-Sitosterol, the main component of Radix Paeoniae Alba, may intervene in the disease through CHRM3. Molecular docking shows ß-Sitosterol has a high affinity with CHRM3, and the interaction between CHRM3 and ß-Sitosterol is the basis of biological activity. The in vitro experiments showed that ß-Sitosterol could significantly up-regulate the mRNA and protein expression levels of both CHRM3 and secretion-related genes in HSG cells. CONCLUSION: Our study shows that the chemical components of Radix Paeoniae Alba have a positive effect on the related mechanism of salivary secretion. We found that ß-Sitosterol can promote the expression of CHRM3, stimulate salivary secretion, treat Sjogren's syndrome and potentially improve its prognosis.

Scanning measurement of surface error and thickness variation of the hemispherical resonator.

Hemispherical resonant gyroscopes (HRGs) are solid-state vibration gyroscopes with the highest precision and are widely used in the aerospace field. The core part of the gyroscope is the resonator, which is a thin-walled hemispherical shell. Surface error and thickness variation of a hemispherical shell causes frequency splitting, which degrades the performance of the HRG. In order to guide the mass leveling of hemispherical resonator, this paper presents a new method for scanning measurement of the surface error and thickness variation of hemispherical resonators. First, a multi-axis platform is designed for noncontact sensor scanning measurements along the meridian and latitudinal lines of the hemispherical resonator. Second, the error model of the measurement system is established. The surface error of the standard sphere is measured to calibrate and compensate for the assembly errors of the measuring device. In addition, the identification accuracy of assembly errors and the influence of assembly errors on thickness measurement are simulated by a computer. Finally, the surface error and thickness variation of the hemispherical resonators are measured. The method is experimentally demonstrated and validated with a wavefront interferometry test. The results show that the method can achieve high precision and high repeatability, which is instructive for assessment of the machining error and further evaluation of the hemispherical resonator.

Screening of six cation exchange resins for high binding capacity, monomer purity and step yield: A case study.

Cation exchange (CEX) chromatography has been widely used as a polishing step in downstream processing of therapeutic monoclonal antibodies (mAbs). It has been well documented that the performance of a particular CEX resin heavily relies on buffer type, pH and conductivity. In this work, with a case study, we screened six commercial CEX resins under different pHs and conductivities. Initial screening was conducted on Tecan to find conditions under which high binding capacity was achieved. Next, performance of each resin was further evaluated using a small column under the identified optimum binding conditions. Variations in binding capacity and purity of eluate were observed among these resins. The adopted approach allows for identification of resins exhibiting good binding capacity, aggregate clearance and recovery.

Prevalence of sarcopenia was higher in women than in men: a cross-sectional study from a rural area in eastern China.

Background: There were limited studies specifically evaluating whether the difference of the prevalence of sarcopenia exists in men and women in older adults from rural areas in China. The aim of this study was to compare the prevalence of sarcopenia between men and women in a rural area in eastern China and to explore the underlying causes. Methods: This study included 1,105 participants aged 60-89 years. Muscle mass was measured by bio-electrical impedance analysis. Hand grip strength was measured by Jamar Hydraulic Hand Dynamometer. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia-2019 Consensus. Data were analyzed using log-binomial and linear regression. Results: The prevalence of sarcopenia was 21.7% in women and 12.9% in men among the study cohort. After adjusting for age, education level, number of diseases, income level, smoking, drinking, and eating habits, proportion of people with sarcopenia was 1.49-fold greater in women than in men (PR = 1.49, 95% CI [1.01-2.26], P = 0.055). Conclusions: The prevalence of sarcopenia in elderly women in this rural area of eastern China is higher than in men, suggesting that women in rural areas in China seem to be more vulnerable for sarcopenia, thus early screening and prevention need to be provided for them to address such gender disparity in health.

The direct and indirect effects of length of hospital stay on the costs of inpatients with stroke in Ningxia, China, between 2015 and 2020: A retrospective study using quantile regression and structural equation models.

Importance: Length of hospital stay (LOHS) is the main cost-determining factor of hospitalization for stroke patients. However, previous analyses involving LOHS did not consider confounding or indirect factors, or the effects of other factors on LOHS and inpatient costs. Objective: To investigate the direct and indirect effects of LOHS on the hospitalization costs of inpatients with ischemic and hemorrhagic stroke. Design setting and participants: This was a population-based, retrospective, and observational study that analyzed data acquired from the Nationwide Inpatient Sample between 2015 and 2020 relating to ischemic and hemorrhagic stroke in Ningxia, China. Main outcomes and measures: Hospitalizations were identified by the International Classification of Diseases 10th Revision (ICD-10). Inpatient costs were described by the median M (P25, P75). We used a quantile regression model to estimate the linear relationships between a group of independent variables X and the quantile of the explained variable hospitalization cost (Y). A structural equation model (SEM) was then used to investigate the direct and indirect effects of LOHS on inpatient costs. Results: The study included 129,444 patients with ischemic stroke and 15,525 patients with hemorrhagic stroke. The median LOHS was 10 (8-13) days for ischemic stroke and 15 (10-22) days for hemorrhagic stroke. The median M (P25, P75) of inpatient costs was $1020 (742-1545) for ischemic stroke and 2813 (1576-6191) for hemorrhagic stroke. The total effect of LOHS on inpatient costs was 0.795 in patients with ischemic stroke. The effect of yearof discharge (X4) and CCI (X8) on inpatient costs was dominated by an indirect effect through the LOHS. The indirect effect was -0.071 (84.52% of the total effect value) and 0.034 (69.39% of the total effect value), respectively. The total effect of LOHS on inpatient costs in patients with hemorrhagic stroke was 0.754. The influence of CCI on inpatient costs was dominated by an indirect effect through LOHS; the indirect effect value was -0.028 (77.78% of the total effect value). The payment type, surgery, method of discharge, and hospital level also exerted an impact on inpatient costs by direct and indirect effects through the LOHS. Conclusions and relevance: Length of hospital stay (LOHS) was identified as the main factor influencing hospitalization costs. However, other social factors were shown to indirectly influence hospitalization costs through the LOHS. Taking effective measures to further reduce hospitalization costs remains an effective way to control hospitalization costs for stroke patients.

Erythrocyte Membrane-Coated Invisible Acoustic-Sensitive Nanoparticle for Inducing Tumor Thrombotic Infarction by Precisely Damaging Tumor Vascular Endothelium.

Selective induction of tumor thrombus infarction is a promising antitumor strategy. Non-persistent embolism due to non-compacted thrombus and activated fibrinolytic system within the tumor large blood vessels and tumor margin recurrence are the main therapeutic bottlenecks. Herein, an erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle (TXA+DOX/PFH/RBCM@cRGD) is described, which can induce tumor thrombus infarction by precisely damaging tumor vascular endothelium. It is revealed that TXA+DOX/PFH/RBCM@cRGD can effectively accumulate on the endothelial surface of tumor vessels with the help of the red blood cell membrane (RBCM) stealth coating and RGD cyclic peptide (cRGD), which can be delivered in a targeted manner as nanoparticle missiles. As a kind of phase-change material, perfluorohexane (PFH) nanodroplets possess excellent acoustic responsiveness. Acoustic-sensitive missiles can undergo an acoustic phase transition and intense cavitation with response to low-intensity focused ultrasound (LIFU), damaging the tumor vascular endothelium, rapidly initiating the coagulation cascade, and forming thromboembolism in the tumor vessels. The drugs loaded in the inner water phase are released explosively. Tranexamic acid (TXA) inhibits the fibrinolytic system, and doxorubicin (DOX) eliminates the margin survival. In summary, a stealthy and acoustically responsive multifunctional nanoparticle delivery platform is successfully developed for inducing thrombus infarction by precisely damaging tumor vascular endothelium.

A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1.

The aberrant expression or genomic mutations of microRNA are associated with several human diseases. This study analyzes the relationship between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 subjects. All these ten SNPs were on or near mature microRNAs. We identified the association between bipolar disorder and the T/C polymorphism at rs895819. To illustrate the function of miR-27a, we constructed several miR-27a knockout (KO) cell lines, determined candidates of miR-27a, and then verified NCAM1 as a target gene of miR-27a. Further studies revealed that the T/C polymorphism on miR-27a led to the differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Furthermore, the C mutation on pre-miR-27a suppresses cell migration and dopamine expression levels. Our study highlights the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.

Antidepressant Sertraline Is a Broad-Spectrum Inhibitor of Enteroviruses Targeting Viral Entry through Neutralization of Endolysosomal Acidification.

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs as of yet to treat EV71 infections. In this study, we conducted antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug's antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be greatly relieved by exposing virus-infected cells to extracellular low-pH culture media. Ultimately, we have identified a use for an FDA-approved antidepressant in broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

Sarcopenia is associated with the presence of nonalcoholic fatty liver disease in Zhejiang Province, China: a cross-sectional observational study.

BACKGROUND: Currently, both non-alcoholic fatty liver disease (NAFLD) and sarcopenia have attracted extensive attention in public health. However, the relationship between NAFLD and sarcopenia remains unclear. This study aimed to clarify the sex-specific association between sarcopenia and NAFLD according to the Asian Working Group for Sarcopenia (AWGS). METHODS: Dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography were measured in 578 participants (92 men and 486 women) during their annual health examinations. Multivariate logistic regression models were used to explore the association between NAFLD and sarcopenia with its two components. RESULTS: A total of 154 participants (30 men and 124 women) had NAFLD. The prevalence of sarcopenia was higher among the participants with NAFLD than among those without NAFLD (men: 20.0% vs. 9.7%, P = 0.295, women: 15.3% vs. 8.0%, P = 0.019). Low muscle mass (LMM) was independently associated with NAFLD in both men and women (men: odds ratio [OR], 2.88; 95% confidence interval [CI] 1.52-5.46; women: OR, 2.08; 95% CI 1.63-2.67). However, low muscle strength (LMS) was independently associated with NAFLD only in male participants, with an OR of 1.15 (95% CI 1.02-1.28). CONCLUSION: The occurrence of sarcopenia was associated with a higher risk of NAFLD, especially in men, as demonstrated by lower muscle mass and lower muscle strength.