Oral soluble shell prepared from OSA starch incorporated with tea polyphenols for the microencapsulation of Sichuan pepper oleoresin: Characterization, flavor stability, release mechanisms and its application in mooncake.

The market share of Sichuan pepper oleoresin (SPO) in the flavor industry is increasing steadily; however, its high volatility, low water solubility, and poor stability continue to pose significant challenges to application. The microencapsulation prepared by emulsion embedding and spray drying is considered as an effective technique to solve the above problems. Sodium octenyl succinate starch (OSA starch) and tea polyphenols (TPs) were used to develop OSA-TPs complex as encapsulants for SPO to prepare orally soluble microcapsules. And the optimum doping of TPs was determined. SPO microcapsules have good properties with high encapsulation efficiency up to 88.13 ± 1.48% and high payload up to 41.58 ± 1.86% with low water content and high heat resistance. The binding mechanism of OSA starch with TPs and its regulation mechanism and effect on SPOs were further analyzed and clarified. The binding mechanism between OSA starch and TPs was clarified in further analyses. The OSA-TPs complexes enhanced the rehydration, release in food matrix and storage stability of SPO, and exhibited good sensory immediacy. Flavor-improved mooncakes were successfully developed, achieving the combination of mooncake flavor and SPO flavor. This study provided a valuable way to prepare flavoring microcapsules suitable for the catering industry, opened up the combined application of SPO and bakery ingredients, and was of great practical value and significance for improving the processing quality of flavor foods, driving the development of the SPO industry, and enhancing the national dietary experience.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

N6AMT1 is a novel potential diagnostic, prognostic and immunotherapy response biomarker in pan-cancer.

BACKGROUND: The N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) is the only writer responsible for DNA 6mA modifications. At present, its role in cancer is still unclear, and further systematic pan-cancer analysis is needed to explore its value in diagnosis, prognosis and immunological function. METHODS: The subcellular localization of N6AMT1 was explored by UniProt and HPA database. The expression data and prognosis data of N6AMT1 were downloaded from the UCSC (cohort: TCGA pan-cancer), and the diagnostic and prognostic value of N6AMT1 in pan-cancer was explored. The value of N6AMT1-guided immunotherapy was explored through three cohorts (GSE168204, GSE67501 and IMvigor210 cohort). The correlation between N6AMT1 expression and tumor immune microenvironment was explored using CIBERSORT and ESTIMATE calculation methods, combined with TISIDB database. The biological role of N6AMT1 in specific tumors was explored by GSEA method. Finally, we explored chemicals affecting N6AMT1 expression through the CTD. RESULTS: N6AMT1 is mainly localized in the nucleus and differentially expressed in 9 cancer types. In addition, N6AMT1 showed early diagnostic value in 7 cancers and showed potential prognostic value in multiple cancer types. We also demonstrated that N6AMT1 expression was significantly associated with immunomodulator-related molecules, infiltration of lymphocyte subsets, and biomarkers of immunotherapy response. Furthermore, we show that N6AMT1 is differentially expressed in the immunotherapy cohort. Finally, we explored 43 chemicals that can affect N6AMT1 expression. CONCLUSIONS: N6AMT1 has shown excellent diagnostic and prognostic capabilities in a variety of cancers, and it may reshape the tumor microenvironment and contribute to the ability to predict response to immunotherapy.

The progress on the relationship between gut microbiota and immune checkpoint blockade in tumors.

Immune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings.

An environmentally insensitive fluorescent probe for G4 DNA detection: Design, synthesis, and mechanism studies.

G4 DNA structure highly localized to functionally important sites within the human genome, has been identified as a biomarker for regulation of multiple biological processes. Identification G4-responsive fluorescence probes has broad application prospects for addressing G4 biological functions, as well as developing of new families of anticancer drugs. However, some currently designed G4 DNA probes may suffer from serious solvent-dependent effect, and cause unspecific fluorescence that masks the specific signal from G4 DNA. Herein, with a bulky imidazole-cored molecular rotor fusing in D-A building block of carbazole-pyridinium, we constructed a new probe ACPS. This new probe with desirable environmentally insensitive property exhibited a "fluorescence-off" state in various polarity solvents. In the presence of G4 DNA, the intra-molecular rotations would be restricted, triggering intense fluorescence enhancement. Especially, probe ACPS bound to G4 DNA structures with superior selectivity, exhibiting much weaker fluorescence response in the presence of non-G4 DNA structures. This probe was also able to realize fluorescence visualization in cell imaging. Collectively, the probe design strategy eliminates the background fluorescence caused by uncontrollable environmental polarity change, thereby achieving high-fidelity sensing G4 DNA structures in complicated systems.

Liposomal Doxorubicin: the Sphingomyelin/Cholesterol System Significantly Enhances the Antitumor Efficacy of Doxorubicin.

Doxorubicin (DOX) has a cytotoxic effect on many tumor cells; however, its clinical application is limited owing to its strong side effects. Although Doxil® reduces the cardiotoxicity of free DOX, it has also introduced a new dose-limiting toxicity. In a previous study, a sialic acid-cholesterol conjugate (SA-CH) was synthesized and modified onto the surface of DOX-loaded liposomes to target tumor-associated macrophages (TAMs), further improving the efficacy of DOX-loaded liposomes over that of Doxil®. Meanwhile, the good retention characteristics and promising antitumor ability of sphingomyelin/cholesterol (SM/CH) system for water-soluble drugs have attracted wide attention. Therefore, we aimed to use SA-CH as the target and hydrogenated soybean phosphatidylcholine (HSPC) or egg sphingomyelin (ESM) as the membrane material to develop a more stable DOX-loaded liposome with stronger antitumor activity. The liposomes were evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro release, long-term storage, cytotoxicity, cellular uptake, pharmacokinetics, tumor targetability, and in vivo antitumor activity. In the liposomes prepared using HSPC/CH, sialic acid (SA) modification considerably increased the accumulation of DOX-loaded liposomes in the tumor, thus exerting a better antitumor effect. However, SA modification in DOX-ESL (SA-CH-modified DOX-loaded liposomes prepared by ESM/CH) destroyed the strong retention effect of the ESM/CH system on DOX, resulting in a reduced antitumor effect. Notably, DOX-ECL (DOX-loaded liposome prepared by ESM/CH) had the optimal storage stability, lowest toxicity, and optimal antitumor effect due to better drug retention properties. Thus, the ESM/CH liposome of DOX is a potential drug delivery system. Sketch of the effect of two DOX-loaded liposomes with hydrogenated soybean phospholipid (HSPC) and egg sphingomyelin (ESM) as lipid membrane material and surface-modified SA derivative on tumor growth inhibition.

Rotator cuff tear reaching the superior half portion of the humeral head causes shoulder abduction malfunction.

PURPOSE: To examine the biomechanical properties governing posterosuperior rotator cuff (RC) tear progression and dynamic shoulder abduction function, in the absence of excess loading. METHODS: Twelve freshly frozen cadaveric shoulders were evaluated via an established dynamic shoulder abduction stimulator. The shoulder abduction functions were primarily evaluated using subacromial contact pressure (SACP) during an abduction procedure, and subsequent middle deltoid force (MDF) under 5 conditions: (1) intact, (2) anterior 1/3 posterosuperior rotator cuff (PSRC) tear, (3) anterior 2/3 PSRC tear, (4) entire PSRC tear, and (5) global RC tear (tear involving the entire superior RC). RESULTS: No obvious differences were observed in the peak MDF required for abduction, and in the peak SACP among the four PSRC tear statuses (49.8 ± 9.2 N, 0.39 ± 0.05 mPa [1/3 PSRC tear]; 49.3 ± 6.8 N, 0.40 ± 0.06 mPa [2/3 PSRC tear]; 51.6 ± 7.0 N, 0.44 ± 0.08 mPa [entire PSRC tear]), as well as intact statuses (48.3 ± 9.8 N, 0.40 ± 0.05 mPa). However, significant elevations in the peak MDF and peak SACP levels were observed among the four PSRC tear statuses and global RC tear (68.1 ± 9.3 N; 4.12 ± 1.50 mPa, P < 0.01). CONCLUSION: In the absence of excess loading, the biomechanical function of the shoulder was not impaired by a simple PSRC tear. However, once the tear size reached the half superior portion of the humeral head, the humeral head migrated to the surface of the subacromion, and this action markedly decreased shoulder abduction function.

Quinoa protein isolate-gum Arabic coacervates cross-linked with sodium tripolyphosphate: Characterization, environmental stability, and Sichuan pepper essential oil microencapsulation.

Quinoa protein isolate-gum Arabic coacervates (QPI-GA coacervates) was cross-linked with sodium tripolyphosphate (STPP) to enhance their physicochemical properties. The optimum concentration of STPP for cross-linking was determined experimentally to be 0.2 g/g of QPI-GA mixture. After cross-linking, QPI-GA coacervates changed to the more ordered structure, and showed higher pH, ionic, and thermal stability. The STPP cross-linked coacervates were used as wall materials for Sichuan pepper essential oil (SPEO) encapsulation with encapsulation efficiency of 87.25 %. Compared with uncross-linked microcapsules, cross-linked microcapsules showed higher SPEO retention at high temperature, different pH, and high ionic concentration. Meanwhile, STPP cross-linked microcapsules improved the stability of SPEO during oral and gastric digestion as indicated by the lower SPEO release, which guaranteed the higher release and absorption in intestinal digestion of SPEO. Consequently, STPP cross-linked QPI-GA coacervates can be an ideal carrier for flavors or active ingredients, protecting them against harsh environment conditions during food processing and digestion.

A One-Dimensional Dynamic Constitutive Modeling of Ethylene Vinyl Acetate (EVA) Foam.

Ethylene vinyl acetate copolymer (EVA) is good for impact protection and energy absorption, and belongs to rate sensitive-dependent materials. This study aimed to investigate the influence of increased strain rate and the presence of entrapped air on the enhancement of foam material strength. The compression deformation behavior of EVA foams containing a microporous structure was extensively investigated over different strain rates of 0.0017/s, 0.033/s, and 0.17/s, where each test was conducted at a constant compression velocity. A one-dimensional dynamic constitutive model was established to describe the large deformation response of EVA to different strain rates. The model included two components, the material action part and the air pressure part. Quasi-static and dynamic compression tests were used to determine the constitutive relations of three parameters, a1, a2, and the leaking rate δ·. The samples with EVA foams at different strain rates were fitted using ORIGIN software, and the constitutive model parameters were obtained. It was found that the ratio of the air leaking rate to the strain rate gradually decreases, causing air within the EVA to be trapped in the cells rather than escaping in a timely manner with increasing strain rates.

Antitumor Immunotherapy of Sialic Acid and/or GM1 Modified Coenzyme Q10 Submicron Emulsion.

Immunotherapy is a novel therapeutic approach for controlling and killing tumor cells by stimulating or reconstituting the immune system, among which T cells serve as immune targets. Herein, we used coenzyme Q10 (CoQ10), which has both immune activation and avoids adverse reactions, as a model drug and developed four CoQ10 submicron emulsions modified with sialic acid (SA) and/or monosialotetrahexosyl ganglioside (GM1). On the one hand, SA interacts with L-selectins on the surface of T cells after entering the circulatory system, leading to activation of T cells and enhancement of antitumor immune responses. On the other hand, owing to its immune camouflage, GM1 can prolong the circulation time of the preparation in the body, thereby increasing the accumulation of the drug at the tumor site. In vitro and in vivo experiments showed that SA-modified preparations exhibited stronger immune activation and inhibition of tumor proliferation. Pharmacokinetic experiments showed that GM1-modified preparations have longer circulation times in vivo. However, SA and GM1 co-modification did not produce a synergistic effect on the preparation. In conclusion, the SA-modified CoQ10 submicron emulsion (Q10-SE) showed optimal antitumor efficacy when administered at a medium dose (6 mg CoQ10 kg-1). In this study, the submicron emulsion model was used as a carrier, and the tumor-bearing mice were used as animal models. In addition, CoQ10 submicron emulsion was modified with SA-CH with active targeting function and/or GM1 with long-circulation function to explore the antitumor effects of different doses of CoQ10 submicron emulsion, and to screen the best tumor immunotherapy formulations of CoQ10.

An Application of Tumor-Associated Macrophages as Immunotherapy Targets: Sialic Acid-Modified EPI-Loaded Liposomes Inhibit Breast Cancer Metastasis.

Breast cancer metastasis is an important cause of death in patients with breast cancer and is closely related to circulating tumor cells (CTCs) and the metastatic microenvironment. As the most infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs), which highly express sialic acid (SA) receptor (Siglec-1), are closely linked to tumor progression and metastasis. Furthermore, the surface of CTCs also highly expressed receptor (Selectin) for SA. A targeting ligand (SA-CH), composed of SA and cholesterol, was synthesized and modified on the surface of epirubicin (EPI)-loaded liposomes (EPI-SL) as an effective targeting delivery system. Liposomes were evaluated for characteristics, stability, in vitro release, cytotoxicity, cellular uptake, pharmacokinetics, tumor targeting, and pharmacodynamics. In vivo and in vitro experiments showed that EPI-SL enhanced EPI uptake by TAMs. In addition, cellular experiments showed that EPI-SL could also enhance the uptake of EPI by 4T1 cells, resulting in cytotoxicity second only to that of EPI solution. Pharmacodynamic experiments have shown that EPI-SL has optimal tumor inhibition with minimal toxicity, which can be ascribed to the fact that EPI-SL can deliver drugs to tumor based on TAMs and regulate TME through the depletion of TAMs. Our study demonstrated the significant potential of SA-modified liposomes in antitumor metastasis. Schematic diagram of the role of SA-CH modified EPI-loaded liposomes in the model of breast cancer metastasis.

Selective c-MYC G4 DNA recognition based on a fluorescent light-up probe with disaggregation-induced emission characteristics.

The c-MYC promoter is well-known as an important oncogene, the overexpression of which leads to ∼80% of all solid tumors. The four-stranded G4 present in the c-MYC promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Accordingly, strategies employed for c-MYC G4 DNA sensing have implications for the detection of many human pathologies. However, achieving specificity toward c-MYC G4 over other structurally similar G4s is a challenging task. Here, a supramolecular strategy that relies on the recognition-driven disaggregation of a novel BODIPY probe is outlined. The synthesized probe remained almost non-fluorescent in aqueous media in the aggregation state. Of all the tested G4 and non-G4 DNAs, only c-MYC triggered probe disaggregation and induced a significant increase in fluorescence intensity. The binding details discussed here suggest the basis for the recognition of a particular G4 structure, thus opening up a new way for the design and development of sequence-selective supramolecular G4 probes with desired properties.

Development of Biomimetic Hepatic Lobule-Like Constructs on Silk-Collagen Composite Scaffolds for Liver Tissue Engineering.

Constructing an engineered hepatic lobule-mimetic model is challenging owing to complicated lobular architecture and crucial hepatic functionality. Our previous study has demonstrated the feasibility of using silk fibroin (SF) scaffolds as functional templates for engineering hepatic lobule-like constructs. But the unsatisfactory chemical and physical performances of the SF-only scaffold and the inherent defect in the functional activity of the carcinoma-derived seeding cells remain to be addressed to satisfy the downstream application demand. In this study, SF-collagen I (SFC) composite scaffolds with improved physical and chemical properties were fabricated, and their utilization for bioengineering a more hepatic lobule-like construct was explored using the immortalized human hepatocyte-derived liver progenitor-like cells (iHepLPCs) and endothelial cells incorporated in the dynamic culture system. The SFC scaffolds prepared through the directional lyophilization process showed radially aligned porous structures with increased swelling ratio and porosity, ameliorative mechanical stiffness that resembled the normal liver matrix more closely, and improved biocompatibility. The iHepLPCs displayed a hepatic plate-like distribution and differentiated into matured hepatocytes with improved hepatic function in vitro and in vivo. Moreover, hepatocyte-endothelial cell interphase arrangement was generated in the co-culture compartment with improved polarity, bile capillary formation, and enhanced liver functions compared with the monocultures. Thus, a more biomimetic hepatic lobule-like model was established and could provide a valuable and robust platform for various applications, including bioartificial liver and drug screening.

Nonalcoholic fatty liver disease, serum cytokines, and dementia among rural-dwelling older adults in China: A population-based study.

BACKGROUND AND PURPOSE: Little is known about whether nonalcoholic fatty liver disease (NAFLD) is associated with dementia or the role of serum proinflammatory cytokines in the association. We aimed to investigate the interrelationships of NAFLD, serum cytokines, and dementia among rural-dwelling older adults. METHODS: This population-based cross-sectional study included 5129 participants (aged ≥60 years; 61.79% women) who were living in rural communities and examined in March 2018-September 2018. NAFLD was defined through transabdominal ultrasound examination in the absence of hepatitis B or excessive alcohol consumption. Serum cytokines were measured in a subsample (n = 1686). Dementia, Alzheimer disease (AD), and vascular dementia (VaD) were diagnosed following international criteria. Data were analyzed with logistic regression and mediation models. RESULTS: Of the 5129 participants, 455 (8.87%) were detected with moderate-to-severe NAFLD, and 292 (5.69%) were diagnosed with dementia (188 with AD and 96 with VaD). The multivariable adjusted odds ratios associated with moderate-to-severe (vs. no-to-mild) NAFLD were 2.22 (95% confidence interval [CI] = 1.41-3.49) for all-cause dementia, 1.88 (95% CI = 1.01-3.50) for AD, and 2.62 (95% CI = 1.33-5.17) for VaD. In the cytokine subsample, controlling for multiple potential confounders, moderate-to-severe NAFLD was significantly associated with higher levels of serum monocyte chemotactic protein-1, interleukin-17A, interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-α (P < 0.05). The mediation analysis showed that IL-6 mediated 12.56% of the association between NAFLD and VaD. CONCLUSIONS: Moderate-to-severe nonalcoholic fatty liver disease is associated with dementia and AD, especially with VaD, among rural-dwelling Chinese older adults, in which the association with VaD is partly mediated by serum inflammatory cytokines.

Bankart Repair With Transferred Long Head of the Biceps Provides Better Biomechanical Effect Than Conjoined Tendon Transfer in Anterior Shoulder Instability With 20% Glenoid Defect.

PURPOSE: To examine the biomechanical differences between labral repair with transferred conjoined tendon and transferred long head of the biceps tendon (LHBT) for anterior shoulder instability with 20% bone loss. METHODS: Twelve cadaveric shoulders were tested in sequent 5 conditions: intact, 20% glenoid defect, Bankart repair, Bankart repair with transferred conjoined tendon (dynamic conjoined tendon sling, DCS), and with transferred LHBT (dynamic LHBT sling, DLS) at 60° of glenohumeral abduction and 60° of external rotation. The physiological glenohumeral joint load was created by forces applied to the rotator cuff, conjoined tendon, and LHBT. The glenohumeral compression force and range of motion were recorded before anteroinferior force application. The anterior, inferior, and total translations were measured with 20, 30, 40, and 50 N of anteroinferior force, respectively. RESULTS: Anteroinferior glenoid defect led to significant increase of humerus translation and decrease of glenohumeral compression force. DLS provided better resistance effect in both anterior-posterior and superior-inferior directions than DCS under high loading condition (40 N, P =.03; 50 N, P <.01). Both DCS and DLS procedures could further restore glenohumeral compression force with Bankart repair (Bankart repair: 32.1 ± 4.0 N; DCS: 36.7 ± 3.2 N, P < .01; DLS: 35.8 ± 3.6 N, P =.03). No range of motion restrictions were observed relative to the normal shoulder. CONCLUSIONS: Both the DLS and DCS techniques could reduce the anterior-inferior translation and partially restore the glenohumeral stability in anterior shoulder instability with 20% anteroinferior glenoid defect compared with Bankart repair. Under greater loading conditions, DLS provides better stability than DCS. CLINICAL RELEVANCE: Shoulder stability can be restored by DLS and DCS with low load. With greater shoulder stability requirements, DLS might be a better option than DCS for anterior shoulder instability with 20% bone loss.

Associations of Fentanyl, Sufentanil, and Remifentanil With Length of Stay and Mortality Among Mechanically Ventilated Patients: A Registry-Based Cohort Study.

Background: As the first-line treatment for mechanically ventilated patients with critical illness, fentanyl and its analogs (e.g., sufentanil and remifentanil) are commonly used in the intensive care unit (ICU). However, the pharmacokinetics, metabolism, and potency of these agents differed. Their effects on clinical outcomes have not been well-understood. Materials and Methods: Using a well-established registry, we conducted a cohort study. Patients who consistently underwent mechanical ventilation (MV) for more than 24 h were identified. We used a time-varying exposure definition, in which we coded each type of opioids as prescribed or not prescribed on each day from initiation of MV to extubation and ICU discharge. We used Fine-Gray competing risk models to compare the effects of fentanyl, sufentanil, and remifentanil on hazards for extubation, ventilator mortality, ICU discharge, and ICU mortality. All models were adjusted using a combination of fixed-time and time-varying covariates. Missing data were imputed using multiple imputation by chained equations. Results: A total of 8,165 patients were included. There were, respectively, 4,778, 4,008, and 2,233 patients receiving at least 1 day of fentanyl, sufentanil, and remifentanil dose. Compared to fentanyl, sufentanil was associated with shorter duration to extubation (hazard ratio 1.31, 95% CI, 1.20-1.41) and ICU discharge (hazard ratio 1.63, 95% CI, 1.38-1.92), and remifentanil was associated with shorter duration to extubation (hazard ratio 1.60, 95% CI, 1.40-1.84) and ICU discharge (hazard ratio 2.02, 95% CI, 1.43-2.84). No significant differences in time to extubation (Hazard ratio 1.14, 95% CI, 0.92-1.41) and ICU discharge (Hazard ratio 1.31, 95% CI, 0.81-2.14) were found between sufentanil and remifentanil. No differences were observed between any two of the agents regarding ventilator mortality or ICU mortality. The effects were similar in patients with versus without surgery. Conclusion: Sufentanil and remifentanil may be superior to fentanyl in shortening the time to extubation and ICU discharge. The effects on ventilator mortality and ICU mortality appeared similar across these agents, while further research is warranted.

Radially Aligned Porous Silk Fibroin Scaffolds as Functional Templates for Engineering Human Biomimetic Hepatic Lobules.

Bioengineering functional hepatic tissue constructs that physiologically replicate the human native liver tissue in vitro is sought for clinical research and drug discovery. However, the intricate architecture and specific biofunctionality possessed by the native liver tissue remain challenging to mimic in vitro. In the present study, a versatile strategy to fabricate lobular-like silk protein scaffolds with radially aligned lamellar sheets, interconnected channels, and a converging central cavity was designed and implemented. A proof-of-concept study to bioengineer biomimetic hepatic lobules was conducted through coculturing human hepatocytes and primary endothelial cells on these lobular-like scaffolds. Relatively long-term viability of hepatocyte/endothelial cells was found along with cell alignment and organization in vitro. The hepatocytes showed special epithelial polarity and bile duct formation, similar to the liver plate, while the aligned endothelial cells generated endothelial networks, similar to natural hepatic sinuses. This endowed the three-dimensional (3D) tissue constructs with the capability to recapitulate hepatic-like parenchymal-mesenchymal growth patterns in vitro. More importantly, the cocultured hepatocytes outperformed monocultures or monolayer cultures, displaying significantly enhanced hepatocyte functions, including functional gene expression, albumin (ALB) secretion, urea synthesis, and metabolic activity. Thus, this functional unit with a biomimetic phenotype provides a novel technology for bioengineering biomimetic hepatic lobules in vitro, with potential utility as a building block for bioartificial liver (BAL) engineering or as a robust tool for drug metabolism investigation.

Design, synthesis and mechanistic studies of a TICT based fluorogenic probe for lighting up protein HSA.

Human serum albumin (HSA) in blood serves as an important biomarker for clinical diagnosis, and fluorescence sensing method has attracted extensive attention. In this work, a small organic molecule probe, YS8, involving twisted intramolecular charge transfer (TICT) characteristic, was designed and investigated to detect HSA. YS8 kept silent state in fluorescence under physiological conditions, but the encapsulation of YS8 in the hydrophobic subdomain IB region of HSA inhibited the TICT state and produced a clear light-up fluorescent signal. Especially, YS8 was demonstrated to be an efficient fluorogenic probe to discriminate HSA from other proteins including the bovine serum albumin (BSA). Moreover, YS8/HSA complex could be applied in fluorescence imaging in living cells and is also useful in the study of artificial fluorescent protein (AFP).

"Highly Exposed Chinese Herbal Medicine" Combined With Apatinib as Maintenance Treatment Following First-Line or Second-Line Chemotherapy for Extensive-Stage Small-Cell Lung Cancer: A Single-Arm, Prospective Study.

This study aimed to evaluate the efficacy and safety of "highly exposed Chinese herbal medicine" combined with apatinib as maintenance treatment following first-line or second-line chemotherapy in patients with ES-SCLC. A total of 23 patients with ES-SCLC were included in this single-arm prospective study (ChiCTR2100045255). "Highly exposed Chinese herbal medicine" combined with apatinib was administered each day after the chemotherapy for maintenance treatment. The primary endpoint of the study was median PFS, while the secondary endpoints included median OS, DCR, ORR, AE, and the association of "highly exposed Chinese herbal medicine" with PFS and OS. Three and 16 patients achieved partial response (PR) and stable disease (SD), respectively, and four patients were with disease progression (PD). The ORR of the patients was 13.0%, DCR was 83.0%, median PFS was 5.0 months, and median OS was 18.0 months. The major AE included secondary hypertension and hand-foot syndrome. Oral intake of Chinese herbal medicine for ≥ 6 months was associated with longer PFS. Hand-foot syndrome was an independent predictive factor for PFS. The statistical analysis suggested no independent influencing factors for OS. "Highly exposed Chinese herbal medicine" combined with apatinib is effective and relatively safe as the maintenance treatment for ES-SCLC patients who undergo first-line or second-line chemotherapy.

Reconstruction and analysis of a genome-scale metabolic model for Agrobacterium tumefaciens.

The plant pathogen Agrobacterium tumefaciens causes crown gall disease and is a widely used tool for generating transgenic plants owing to its virulence. The pathogenic process involves a shift from an independent to a living form within a host plant. However, comprehensive analyses of metabolites, genes, and reactions contributing to this complex process are lacking. To gain new insights about the pathogenicity from the viewpoints of physiology and cellular metabolism, a genome-scale metabolic model (GSMM) was reconstructed for A. tumefaciens. The model, referred to as iNX1344, contained 1,344 genes, 1,441 reactions, and 1,106 metabolites. It was validated by analyses of in silico cell growth on 39 unique carbon or nitrogen sources and the flux distribution of carbon metabolism. A. tumefaciens metabolic characteristics under three ecological niches were modelled. A high capacity to access and metabolize nutrients is more important for rhizosphere colonization than in the soil, and substantial metabolic changes were detected during the shift from the rhizosphere to tumour environments. Furthermore, by integrating transcriptome data for tumour conditions, significant alterations in central metabolic pathways and secondary metabolite metabolism were identified. Overall, the GSMM and constraint-based analysis could decode the physiological and metabolic features of A. tumefaciens as well as interspecific interactions with hosts, thereby improving our understanding of host adaptation and infection mechanisms.