[Effects of maltodextrin on water adsorption and thermodynamic properties of Codonopsis Radix spray-dried powder].

This study aims to reveal the effects of maltodextrin(MD) on the water adsorption and thermodynamic properties of Codonopsis Radix(DS) spray-dried powder by determining the moisture and energy changes of the powder in the process of moisture absorption. The static weighing method was used to obtain the isothermal water adsorption data of the spray-dried powder in 6 saturated salt solutions(KAc, MgCl_2·6H_2O, K_2CO_3, NaBr, NaCl, and KCl) at 3 temperatures(25, 35, and 45 ℃). Six models were used for fitting of the water adsorption process, and the most suitable model was selected based on the model performance. Furthermore, the corresponding net equivalent adsorption heat and differential entropy were calculated, and the adsorption entropy change was integrated. The linear relationship between net equivalent adsorption heat and differential entropy was drawn based on the entropy-enthalpy complementarity theory. The results showed that the water adsorption properties of DS and DS-MD spray-dried powder followed the type Ⅲ isotherm and was well fitted by the GAB model. The monolayer water content M_0 decreased with the increase in temperature. At the same temperature, the M_0 of DS spray-dried powder decreased after the addition of MD. The net equivalent adsorption heat and differential entropy of DS and DS-MD spray-dried powder decreased with the increase in water content, which presented a linear relationship. The addition of MD decreased the water activity corresponding to the lowest integral adsorption entropy of the powder, and the system became more stable. The results indicated that the spray-dried powder became more stable after the addition of MD.

Chemotherapy-Enabled Colorectal Cancer Immunotherapy of Self-Delivery Nano-PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance.

The chemo-regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance of colorectal cancer. In this work, the proteolysis targeting chimera (PROTAC) of BRD4 (dBET57) is found to downregulate colorectal cancer glycolysis through the transcription inhibition of c-Myc, which also inhibits the expression of programmed death ligand 1 (PD-L1) to reverse immune evasion and avoid adaptive immune resistance. Based on this, self-delivery nano-PROTACs (designated as DdLD NPs) are further fabricated by the self-assembly of doxorubicin (DOX) and dBET57 with the assistance of DSPE-PEG2000. DdLD NPs can improve the stability, intracellular delivery, and tumor targeting accumulation of DOX and dBET57. Meanwhile, the chemotherapeutic effect of DdLD NPs can efficiently destroy colorectal cancer cells to trigger a robust immunogenic cell death (ICD). More importantly, the chemo-regulation effects of DdLD NPs can inhibit colorectal cancer glycolysis to reduce the lactate production, and downregulate the PD-L1 expression through BRD4 degradation. Taking advantages of the chemotherapy and chemo-regulation ability, DdLD NPs systemically activated the antitumor immunity to suppress the primary and metastatic colorectal cancer progression without inducing any systemic side effects. Such self-delivery nano-PROTACs may provide a new insight for chemotherapy-enabled tumor immunotherapy.

[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Assessment of Biological Activity of 28-Homobrassinolide via a Multi-Level Comparative Analysis.

Brassinosteroids (BRs) play vital roles in the plant life cycle and synthetic BRs are widely used to increase crop yield and plant stress tolerance. Among them are 24R-methyl-epibrassinolide (24-EBL) and 24S-ethyl-28-homobrassinolide (28-HBL), which differ from brassinolide (BL, the most active BR) at the C-24 position. Although it is well known that 24-EBL is 10% active as BL, there is no consensus on the bioactivity of 28-HBL. A recent outpouring of research interest in 28-HBL on major crops accompanied with a surge of industrial-scale synthesis that produces mixtures of active (22R,23R)-28-HBL and inactive (22S,23S)-28HBL, demands a standardized assay system capable of analyzing different synthetic "28-HBL" products. In this study, the relative bioactivity of 28-HBL to BL and 24-EBL, including its capacity to induce the well-established BR responses at molecular, biochemical, and physiological levels, was systematically analyzed using the whole seedlings of the wild-type and BR-deficient mutant of Arabidopsis thaliana. These multi-level bioassays consistently showed that 28-HBL exhibits a much stronger bioactivity than 24-EBL and is almost as active as BL in rescuing the short hypocotyl phenotype of the dark-grown det2 mutant. These results are consistent with the previously established structure-activity relationship of BRs, proving that this multi-level whole seedling bioassay system could be used to analyze different batches of industrially produced 28-HBL or other BL analogs to ensure the full potential of BRs in modern agriculture.

Carrier-Free Nano-PROTACs to Amplify Photodynamic Therapy Induced DNA Damage through BRD4 Degradation.

Therapy-induced DNA damage is the most common strategy to inhibit tumor cell proliferation, but the therapeutic efficacy is limited by DNA repair machinery. Carrier-free nanoproteolysis targeting chimeras (PROTACs), designed as SDNpros, have been developed to enhance photodynamic therapy (PDT) by blocking the DNA damage repair pathway through BRD4 degradation. Specifically, SDNpros are constructed through noncovalent interactions between the photosensitizer of chlorine e6 (Ce6) and PROTACs of BRD4 degrader (dBET57) via self-assembly. SDNpro has favorable dispersibility and a uniform nanosize distribution without drug excipients. Upon light irradiation, SDNpro produces abundant reactive oxygen species (ROS) to induce DNA oxidative damage. Meanwhile, the DNA repair pathway would be interrupted by the concurrent degradation of BRD4, which could intensify the oxidative DNA damage and elevate PDT efficiency. Beneficially, SDNpro suppresses tumor growth and avoids systemic side effects, providing a promising strategy to promote the clinical translation of PROTACs for tumor treatment.

Effect of Early External Ventricular Drainage on Perihemorrhagic Edema and Functional Outcome in Patients with Intraventricular Hemorrhage.

OBJECTIVE: External ventricular drainage (EVD) is the most common neurosurgical procedure that allows drainage of cerebrospinal fluid and intraventricular blood. A specific time threshold for insertion of an EVD catheter in patients with spontaneous intracerebral hemorrhage and intraventricular hemorrhage has not been established. This study aimed to evaluate the association of early EVD with functional outcome in patients with intracerebral hemorrhage and intraventricular hemorrhage. METHODS: Propensity score matching was used to account for baseline imbalances. Modified Rankin Scale score at 3 and 6 months, mortality rates at 3 and 6 months, postoperative complications, time course of edema evolution, and peak perihemorrhagic edema (PHE) were compared in patients who received early EVD versus routine EVD. RESULTS: The rate of favorable outcome at 3 months was higher in the early EVD group compared with the routine EVD group. There were no differences between groups in modified Rankin Scale score at 6 months or mortality rates at 3 and 6 months. Absolute peak PHE and relative PHE volumes were significantly less in the early EVD group compared with the routine EVD group. The incidence of postoperative infections was lower in the early EVD group compared with the routine EVD group. CONCLUSIONS: Early EVD was associated with improved functional outcome at 3 months, reduced PHE, and lower rate of infection in intracerebral hemorrhage and intraventricular hemorrhage. However, survival at 3 and 6 months and functional outcome at 6 months were not improved.

Prognosis Prediction of Lung Adenocarcinoma Patients Based on Molecular Subgroups of DNA Methylation.

Lung adenocarcinoma (LUAD) is a malignant tumor with high mortality. At present, the clinicopathologic feature is the main breakthrough to assess the prognosis of LUAD patients. However, in most cases, the results are less than satisfactory. Cox regression analysis was conducted in this study to obtain methylation sites with significant prognostic relevance based on mRNA expression, DNA methylation data, and clinical data of LUAD from The Cancer Genome Atlas Program database. LUAD patients were grouped into 4 subtypes according to different methylation levels using K-means consensus cluster analysis. By survival analysis, patients were grouped into high-methylation and low-methylation groups. Later, 895 differentially expressed genes (DEGs) were obtained. Eight optimal methylation signature genes associated with prognosis were screened by Cox regression analysis, and a risk assessment model was constructed based on these genes. Samples were then classified into high-risk and low-risk groups depending on the risk assessment model, and prognostic, predictive ability was assessed using survival and receiver operating characteristic (ROC) curves. The results showed that this risk model had a great efficacy in predicting the prognosis of patients, and it was, therefore, able to be an independent prognostic factor. At last, the enrichment analysis demonstrated that the signaling pathways, including cell cycle, homologous recombination, P53 signaling pathway, DNA replication, pentose phosphate pathway, and glycolysis gluconeogenesis were remarkably activated in the high-risk group. In general, we construct an 8-gene model based on DNA methylation molecular subtypes by a series of bioinformatics methods, which can provide new insights for predicting the prognosis of patients with LUAD.

Additively manufactured polyether ether ketone (PEEK) skull implant as an alternative to titanium mesh in cranioplasty.

173Cranioplasty is used for skull defects, involving lifting the scalp and restoring the contour of the skull with the original skull piece, titanium mesh, or solid biomaterial. Additive manufacturing (AM) technology, known as three-dimensional (3D) printing, is now utilized by medical professionals to develop customized replicas of tissues, organs and bones, offering a valid option with perfect anatomic fitting in the individual and skeletal reconstruction. Here, we report a case that underwent titanium mesh cranioplasty 15 years ago. The poor appearance of the titanium mesh weakened the left eyebrow arch and resulted in the formation of a sinus tract. Cranioplasty was performed using an additively manufactured polyether ether ketone (PEEK) skull implant. PEEK skull implants have been successfully implanted without any complications. To our knowledge, this is the first reported case of direct use of fused filament fabrication (FFF)-fabricated PEEK implant for cranial repair. The FFF-printed PEEK customized skull implant could possess simultaneously with adjustable material thickness and more complex structure, tunable mechanical properties, and low processing costs compared with traditional manufacturing processes. While meeting clinical needs, this production method is an appropriate alternative for promoting the use of PEEK materials in cranioplasty.

Cascade Immune Activation of Self-Delivery Biomedicine for Photodynamic Immunotherapy Against Metastatic Tumor.

Photodynamic therapy (PDT) can generate reactive oxygen species (ROS) to cause cell apoptosis and induce immunogenic cell death (ICD) to activate immune response, becoming a promising antitumor modality. However, the overexpressions of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1) on tumor cells would reduce cytotoxic T cells infiltration and inhibit the immune activation. In this paper, a simple but effective nanosystem is developed to solve these issues for enhanced photodynamic immunotherapy. Specifically, it has been constructed a self-delivery biomedicine (CeNB) based on photosensitizer chlorine e6 (Ce6), IDO inhibitor (NLG919), and PD1/PDL1 blocker (BMS-1) without the need for extra excipients. Of note, CeNB possesses fairly high drug content (nearly 100%), favorable stability, and uniform morphology. More importantly, CeNB-mediated IDO inhibition and PD1/PDL1 blockade greatly improve the immunosuppressive tumor microenvironments to promote immune activation. The PDT of CeNB not only inhibits tumor proliferation but also induces ICD response to activate immunological cascade. Ultimately, self-delivery CeNB tremendously suppresses the tumor growth and metastasis while leads to a minimized side effect. Such simple and effective antitumor strategy overcomes the therapeutic resistance against PDT-initiated immunotherapy, suggesting a potential for metastatic tumor treatment in clinic.

Photodynamic Therapy Initiated Ferrotherapy of Self-Delivery Nanomedicine to Amplify Lipid Peroxidation via GPX4 Inactivation.

Lipid peroxide (LPO) is the hallmark of ferroptosis, which is a promising antitumor modality for its unique advantages. However, a cellular defense system would weaken the antitumor efficacy of ferrotherapy. Herein, a GPX4 inhibitor of ML162 and a photosensitizer of chlorine e6 (Ce6) are used to prepare the self-delivery nanomedicine (C-ML162) through hydrophobic and electrostatic interactions to enhance ferroptosis by photodynamic therapy (PDT). Specifically, carrier-free C-ML162 improves the solubility, stability, and cellular uptake of antitumor agents. Upon light irradiation, the internalized C-ML162 generates large amounts of reactive oxygen species (ROS) to oxidize cellular unsaturated lipid into LPO. More importantly, C-ML162 can directly inactivate GPX4 to enhance the accumulation of toxic LPO, inducing ferroptotic cell death. Additionally, C-ML162 is capable of accumulating at a tumor site for effective treatment. This self-delivery system to amplify lipid peroxidation via GPX4 inactivation for PDT initiated ferrotherapy might provide an appealing strategy against malignancies.

DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits.

Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are commonly used treatments for patients with type 2 diabetes mellitus (T2DM). Both anti-diabetic treatments function by playing key modulatory roles in the incretin system. Though these drugs have been deemed effective in treating T2DM, the Food and Drug Administration (FDA) and some members of the scientific community have questioned the safety of these therapeutics relative to important cardiovascular endpoints. As a result, since 2008, the FDA has required all new drugs for glycemic control in T2DM patients to demonstrate cardiovascular safety. The present review article strives to assess the safety and benefits of incretin-based therapy, a new class of antidiabetic drug, on the health of patient cardiovascular systems. In the process, this review will also provide a physiological overview of the incretin system and how key components function in T2DM.

A better overall survival (OS) for total (ipsilateral) retroperitoneal lipectomy than standard complete resection in patients with retroperitoneal liposarcoma: a comparative multi-institutional study.

Background: Complete resection (CR) serves as the standard of surgical treatment for retroperitoneal liposarcoma (RPLS). Unfortunately, even at referral centers, recurrence rates are high, and CR may not address multifocal diseases, which are a common phenomenon in RPLS. We sought to retrospectively compare the clinical outcomes of RPLS patients treated with total (ipsilateral) retroperitoneal lipectomy (TRL) and CR. Because TRL remove potentially multifocal tumors in the fat, patients may have a better prognosis than CR. Methods: Patients with primary/first-recurrent RPLS who had been treated at 5 referral centers were recruited from December 2014 to June 2018. Multivariable Cox regression analyses were conducted to determine the effects of demographic, operative, and clinicopathological variables on the following primary endpoints: local recurrence (LR), local recurrence-free survival (LRFS), and overall survival (OS). Results: A total of 134 patients were enrolled in this retrospective study, 53 of whom underwent TRL, and 81 of whom underwent CR. The 2 groups were comparable in terms of age, gender, presentation (primary vs. first-recurrent RPLS), number of tumors (unifocal vs. multifocal) at presentation, and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade. The TRL group had higher levels of preoperative hemoglobin (Hb) (13 vs. 12.5 g/dL; P=0.008) and a lower amount of intraoperative blood loss (400 vs. 500 mL; P=0.034), but there were no significant differences in the length of hospital stay (23 vs. 22 d; P=0.47) or complications (32 vs. 30; P=0.82) between the 2 groups. In a subset of patients with multifocal tumors at initial presentation, OS was more prolonged in those treated with TRL than those treated with CR (P=0.0272). Based on the multivariable analysis, primary liposarcoma and a low FNCLCC grade were associated with decreased LR and improved OS. Conclusions: TRL is a safe procedure that positively affects the OS of patients with multifocal RPLS. This novel strategy deserves further investigation in prospective studies.

[Water migration and kinetics of Arecae Semen during moistening process].

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.

C1QTNF6 Targeted by MiR-184 Regulates the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells.

OBJECTIVE: To seek out the mechanism by which C1QTNF6 mediates lung adenocarcinoma (LUAD). METHODS: Differentially expressed mRNAs and miRNAs in LUAD were analyzed using bioinformatics. In LUAD cells, C1QTNF6 mRNA and miR-184 expression were evaluated with qRT-PCR, and C1QTNF6 protein level was assessed by western blot. Cellular behaviors were assessed by colony formation, CCK-8, Transwell, and wound healing methods. The binding ability of miR-184 to C1QTNF6 was observed by dual-luciferase assay. RESULTS: High expression of C1QTNF6 in LUAD stimulated cancer cellular behaviors. MiR-184 was lowly expressed in LUAD and downregulated C1QTNF6 expression. MiR-184 restrained LUAD cell processes by targeting C1QTNF6. CONCLUSION: MiR-184 repressed LUAD cell processes via mediating C1QTNF6. MiR-184 and C1QTNF6 are expected to be indicators for LUAD treatment.

Synchronized early gastric cancer occurred in a patient with serrated polyposis syndrome: A case report.

BACKGROUND: Serrated polyposis syndrome (SPS) is a relatively rare disease that is characterized by multiple serrated lesions/polyps. Very little is known regarding the extracolonic cancers associated with SPS. The genetic basis of the process remains unknown. CASE SUMMARY: A 67-year-old male patient initially presented with belching and abdominal distension for a year as well as diarrhea for over 2 mo. The patient underwent colonoscopy and was diagnosed with serrated polyposis syndrome. Half a year later, a gastroscopy was performed during the postoperative re-examination to screen for other lesions of the upper gastrointestinal tract. An elevated lesion was detected in the anterior wall of the gastric antrum. Curative en bloc resection of the lesion was achieved via endoscopic submucosal dissection. The pathological result was high-grade dysplasia with focal intramucosal carcinoma. Exome sequencing was performed for the patient and five gastric cancer-associated variants (methylenetetrahydrofolate reductase, metaxin 1, coiled-coil domain containing 6, glutamate ionotropic receptor delta type subunit 1, and aldehyde dehydrogenase 1) were identified. CONCLUSION: This paper reports a case that presented with both SPS and early gastric cancer. Genetic mutations that were potentially responsible for this condition were sought by exome sequencing.

MicroRNA-9-5p Facilitates Lung Adenocarcinoma Cell Malignant Progression via Targeting STARD13.

We aimed to elucidate binding of microRNA-9-5p and STARD13 in lung adenocarcinoma (LUAD) cells and discuss their impact on malignant progression of LUAD, so as to provide evidence for identifying new therapeutic targets for LUAD. Bioinformatics analysis was introduced for analysis of differentially expressed miRNAs in LUAD tissue, and potential downstream target gene was predicted with TargetScan and other databases. MicroRNA-9-5p and STARD13 mRNA levels at cellular level was analyzed with qRT-PCR assay. Lipofectamine 2000 was applied for cell transfection. Proliferation, migration and invasion of LUAD cells were assayed with CCK-8, wound healing and Transwell assays, respectively. Protein expression of STARD13 was assessed with western blot. Binding of microRNA-9-5p and STARD13 was identified with dual-luciferase assay. Compared with normal human bronchial cells, microRNA-9-5p level in LUAD cells was noticeably increased, and STARD13 level was noticeably decreased. MicroRNA-9-5p could significantly promote malignant progression of LUAD cells, while forced STARD13 level markedly repress malignant progression of LUAD cells. Dual-luciferase gene assay showed that microRNA-9-5p had a direct targeting relationship with STARD13, and it was also found that microRNA-9-5p enhanced malignant behaviors of LUAD cells through modulating STARD13. STARD13 was a target of microRNA-9-5p in LUAD. MicroRNA-9-5p fostered malignant behaviors of LUAD cells by targeting STARD13. Therefore, microRNA-9-5p may become a new target for LUAD, and microRNA-9-5p inhibition may be a new treatment method.

Self-Delivery Ternary Bioregulators for Photodynamic Amplified Immunotherapy by Tumor Microenvironment Reprogramming.

Abnormal metabolism of cancer cells results in complex tumor microenvironments (TME), which play a dominant role in tumor metastasis. Herein, self-delivery ternary bioregulators (designated as TerBio) are constructed for photodynamic amplified immunotherapy against colorectal cancer by TME reprogramming. Specifically, carrier-free TerBio are prepared by the self-assembly of chlorine e6, SB505124 (SB), and lonidamine (Lon), which exhibit improved tumor accumulation, tumor penetration, and cellular uptake behaviors. Interestingly, TerBio-mediated photodynamic therapy (PDT) could not only inhibit the primary tumor growth but also induce immunogenic cell death of tumors to activate the cascade immune response. Furthermore, TerBio are capable of TME reprograming by SB-triggered transforming growth factor (TGF)-ß blockage and Lon-induced lactic acid efflux inhibition. As a consequence, TerBio significantly suppresses distant and metastatic tumor growth by PDT-amplified immunotherapy. This study might advance the development of self-delivery nanomedicine against malignant tumor growth and metastasis.

Self-Delivery Nanomedicine for Glutamine-Starvation Enhanced Photodynamic Tumor Therapy.

Glutamine metabolism of tumor cells plays a crucial role in maintaining cell homeostasis and reducing oxidative damage. Herein, a valid strategy of inhibiting glutamine metabolism is proposed to amplify the oxidative damage of photodynamic therapy (PDT) to tumor cells. Specifically, the authors develop a drug co-delivery system (designated as CeV) based on chlorine e6 (Ce6) and V9302 via the self-assembly technology. In spite of the strong hydrophobicity of therapeutic agents, the assembled CeV holds a favorable dispersibility in water and an improved cellular uptake capability. Under light irradiation, the internalized CeV is capable of generating abundant reactive oxygen species (ROS) for PDT. More importantly, CeV can reduce the uptake of glutamine through V9302-mediated alanine-serine-cysteine transporter of type-2 (ASCT2) inhibition, leading to a reduced glutathione (GSH) production and an amplified oxidative stress. As a result, CeV has a robust PDT efficacy on tumor inhibition by the blockade of glutamine transport. Notably, CeV exhibits a superiority on tumor suppression over the single treatment as well as the combined administration of Ce6 and V9302, which indicates the advantage of CeV for synergistic treatment. It may serve as a novel nanoplatform for developing a drug co-delivery system to improve PDT efficiency by inhibiting cell metabolism.

[Study on endpoint determination method of tablet coating based on 3σ criteria and logic regression].

This paper explores the statistical distribution characteristics of coating film thickness, so as to present a new method for determining coating endpoint based on 3σ criterion and logic regression. Firstly, the spectrum and thickness of 4 batch samples were collected. Secondly, the spectral range of normal products was obtained by 3σ criterion, with the spectral feature NI as the number of test spectrum in the above range. Then, the model based on 3σ criterion and logic regression was built according to the best condition in K-fold cross-validation and the determined threshold of qualified rate in the coating endpoint. Finally, the qualified rate of test set samples at different time points was calculated by the above model, and the above change trend and the threshold value were combined to determine the coating endpoint. The results of KS analysis showed the distribution of thickness of the qualified products followed the normal distribution(P=0.081>0.05). The accuracy of the coating endpoint determination was as high as 100% by the model based on 3σ criterion and logic regression when the determined threshold of qualified rate was 90%. Therefore, the 3σ criterion was feasible to the research of coating eligibility. This paper reveals certain random phenomena in the coating process, and the method features a high accuracy, quick analysis and a good interpretability, which provides a reference for online detection and qualify evaluation in future.

[Evaluation of Air Pollution Characteristics and Air Quality Improvement Effect in Beijing and Chengdu].

In recent years, China's air quality has been improving, and the concentration of atmospheric particulate matter has decreased significantly. In this study, the pollution characteristics and trends of two typical representative cities (Beijing and Chengdu) were analyzed. The geographical locations, pollution emissions, and meteorological diffusion conditions of the two cities were compared, to evaluate the relative contribution of meteorological conditions and pollution reduction regulations in decreasing fine particulate matter (PM2.5) concentrations. The results showed that the number of heavily polluted days and pollution episodes in Beijing and Chengdu decreased significantly from 2013 to 2018, and the concentration of SO2 and PM2.5 decreased substantially. Compared to 2013, SO2 concentration in Beijing and Chengdu has decreased by 77.8% and 70.9%, whereas PM2.5 concentration has decreased by 42.7% and 48.5%, respectively. The largest reduction appeared in winter, when PM2.5 decreased at an annual rate of 13.5 µg ·m-3 for Beijing and 14.1 µg ·m-3 for Chengdu. During the study period, the wind speed in Chengdu was less than that in Beijing, temperature was approximately 3℃ higher, and static wind in winter was more frequent. A significantly lower mixed-layer height, atmospheric capacity index, and ventilation coefficient in Chengdu resulted in more unfavorable atmospheric diffusion conditions. The static and stable weather index and the environmental meteorological index (EMI) also showed that the atmospheric diffusion conditions were better in Beijing than in Chengdu. The EMI of the two cities showed a decreasing trend during the study period, and the decline in EMI in Chengdu was the most significant in 2018, indicating an evident improvement in meteorological conditions. In 2018, emission reductions are estimated to have contributed 33.5% and 24% to the decrease in PM2.5 in Beijing and Chengdu, respectively, and meteorological conditions contributed 7.2% and 11.1% to the reduction in these two cities. In winter, emission reductions respectively contributed 31.7% and 32.5% to reduction in Beijing and Chengdu, while meteorological conditions made a larger contribution.