Symmetry-Breaking of Nanoparticle Surface Function Via Conformal DNA Design.

Asymmetric surface functionalization of complex nanoparticles to control their directional self-assembly remains a considerable challenge. Here, we demonstrated a conformal DNA design strategy for flexible remodeling of the surface of complex nanoparticles, taking Au nanobipyramids (AuNBPs) as a model. We sheathed one or both tips of AuNBPs into conformal DNA origami with an exceptionally accurate orientation control. Such asymmetrically and symmetrically distributed surface patches possess regioselective, sequence, and site-specific DNA binding capabilities. As a result, we realized a series of prototypical multicomponent "colloidal molecules" made of AuNBPs and Au nanospheres (AuNSs) with defined directionality and number of "bonding valence" as well as 1D and 3D hierarchical assemblies, e.g., inverse core-satellites of AuNBPs and AuNSs, side-by-side and tip-to-tip linear assemblies of AuNBPs, and 3D helical superstructures of AuNBPs with tunable twists. These findings inspire new opportunities for nanoparticle surface engineering and the high-order self-assembly of nanoarchitectures with higher complexity and broadened functionalities.

Nonlinear relationship between platelet count and 30-day in-hospital mortality in intensive care unit stroke patients: a multicenter retrospective cohort study.

Background: Evidence of the relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients is still scarce. Therefore, the purpose of this study was to explore the relationship between platelet count and 30-day in-hospital mortality among ICU stroke patients. Methods: We conducted a multicenter retrospective cohort study using data from 8,029 ICU stroke patients in the US eICU-CRD v2.0 database from 2014 to 2015. Utilizing binary logistic regression, smooth curve fitting, and subgroup analyses, we examined the link between platelet count and 30-day in-hospital mortality. Results: The 30-day in-hospital mortality prevalence was 14.02%, and the mean platelet count of 223 × 109/L. Adjusting for covariates, our findings revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.975, 95% CI: 0.966, 0.984). Subgroup analyses supported the robustness of these results. Moreover, a nonlinear relationship was observed between platelet count and 30-day in-hospital mortality, with the inflection point at 163 × 109/L. On the left side of the inflection point, the effect size (OR) was 0.92 (0.89, 0.95), while on the right side, the relationship was not statistically significant. Conclusion: This study establishes an independent negative association between platelet count and 30-day in-hospital mortality in ICU stroke patients. Furthermore, a nonlinear relationship with a saturation effect was identified, suggesting that maintaining the platelet count around 163 × 109/L can reduce 30-day in-hospital mortality in these patients.

Impact of hepatic inflammation and fibrosis on the recurrence and long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after hepatectomy.

BACKGROUND: Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients' prognoses remains unclear. METHODS: The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan-Meier analysis. RESULTS: Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp < 0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (P = 0.52 and P = 0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all P < 0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (P = 0.48 and P = 0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis. CONCLUSIONS: For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

[Contamination Characteristics and Ecological Risk Assessment of Pharmaceuticals and Personal Care Products in Drains Flowing into the Yellow River of Ningxia].

Pharmaceuticals and personal care products (PPCPs) are a group of emerging contaminants causing detrimental effects on aquatic living organisms even at low doses. To investigate the contamination characteristics and ecological risks of PPCPs in drains flowing into the Yellow River of Ningxia, 21 PPCPs were detected and analyzed using solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry in this study. All 21 targeted compounds were detected in the drains, with total concentrations ranging from 47.52 to 1 700.96 ng·L-1. Ciprofloxacin, acetaminophen, benzophenone-3, and diethyltoluamide were the more commonly detected compounds, with detection frequencies exceeding 80%. The five highest-concentration PPCPs were acetaminophen, diethyltoluamide, caffeine, benzophenone-3, and levofloxacin, with the maximum concentrations of 597.21, 563.23, 559.00, 477.28, and 473.07 ng·L-1, respectively. Spatial analysis showed that the pollution levels of PPCPs in the drains of the four cities were different, with average concentrations of ∑PPCPs in the order of Yinchuan>Shizuishan>Wuzhong>Zhongwei. The total concentration of PPCPs before flowing into the Yellow River ranged from 124.82 to 1 046.61 ng·L-1. Source analysis showed that livestock and poultry breeding wastewater was the primary source for sulfadiazine and oxytetracycline, whereas medical wastewater was the primary source for levofloxacin and ciprofloxacin. The primary sources of triclocarban and triclosan were domestic sewage and industrial wastewater, whereas the primary source of caffeine and diethyltoluamide was domestic sewage. The pollution of diciofenac, cimetidine, triclocarban, and triclosan in the drains was positively correlated with the regional population and economic development level. The ecological risk assessment indicated that levofloxacin, diclofenac, gemfibrozil, benzophenone-3, and triclocarban posed high risks to aquatic organisms in drains flowing into the Yellow River. It is worthwhile to consider the mixture risk of the PPCPs that exhibited high risk at most sampling sites.

Clustering analysis for the evolutionary relationships of SARS-CoV-2 strains.

To explore the differences and relationships between the available SARS-CoV-2 strains and predict the potential evolutionary direction of these strains, we employ the hierarchical clustering analysis to investigate the evolutionary relationships between the SARS-CoV-2 strains utilizing the genomic sequences collected in China till January 7, 2023. We encode the sequences of the existing SARS-CoV-2 strains into numerical data through k-mer algorithm, then propose four methods to select the representative sample from each type of strains to comprise the dataset for clustering analysis. Three hierarchical clustering algorithms named Ward-Euclidean, Ward-Jaccard, and Average-Euclidean are introduced through combing the Euclidean and Jaccard distance with the Ward and Average linkage clustering algorithms embedded in the OriginPro software. Experimental results reveal that BF.28, BE.1.1.1, BA.5.3, and BA.5.6.4 strains exhibit distinct characteristics which are not observed in other types of SARS-CoV-2 strains, suggesting their being the majority potential sources which the future SARS-CoV-2 strains' evolution from. Moreover, BA.2.75, CH.1.1, BA.2, BA.5.1.3, BF.7, and B.1.1.214 strains demonstrate enhanced abilities in terms of immune evasion, transmissibility, and pathogenicity. Hence, closely monitoring the evolutionary trends of these strains is crucial to mitigate their impact on public health and society as far as possible.

The SingHealth Perioperative and Anesthesia Subject Area Registry (PASAR), a large-scale perioperative data mart and registry.

BACKGROUND: To enhance perioperative outcomes, a perioperative registry that integrates high-quality real-world data throughout the perioperative period is essential. Singapore General Hospital established the Perioperative and Anesthesia Subject Area Registry (PASAR) to unify data from the preoperative, intraoperative, and postoperative stages. This study presents the methodology employed to create this database. METHODS: Since 2016, data from surgical patients have been collected from the hospital electronic medical record systems, de-identified, and stored securely in compliance with privacy and data protection laws. As a representative sample, data from initiation in 2016 to December 2022 were collected. RESULTS: As of December 2022, PASAR data comprise 26 tables, encompassing 153,312 patient admissions and 168,977 operation sessions. For this period, the median age of the patients was 60.0 years, sex distribution was balanced, and the majority were Chinese. Hypertension and cardiovascular comorbidities were also prevalent. Information including operation type and time, intensive care unit (ICU) length of stay, and 30-day and 1-year mortality rates were collected. Emergency surgeries resulted in longer ICU stays, but shorter operation times than elective surgeries. CONCLUSIONS: The PASAR provides a comprehensive and automated approach to gathering high-quality perioperative patient data.

Comprehensive analysis of the gut microbiome and post-translational modifications elucidates the route involved in microbiota-host interactions.

The gut microbiome interacts with the host to maintain body homeostasis, with gut microbial dysbiosis implicated in many diseases. However, the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear. This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation. We conducted succinylome analysis of hippocampal proteins in germ-free (GF) and specific pathogen-free (SPF) mice and metagenomic analysis of feces from SPF mice. These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice. Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins, including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice. We constructed a panoramic map of gut microbiota-regulated succinylation, acetylation, and phosphorylation, and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways. Pearson correlation analysis indicated that 13 taxa, predominantly belonging to the Bacteroidetes phylum, were correlated with the biological functions of post-translational modifications. Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways. This study highlights the hippocampal physiological changes induced by the absence of gut microbiota, and proteomic quantification of succinylation, phosphorylation, and acetylation, contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

DNA-Modulated and Mechanoresponsive Excitonic Couplings Reveal Chiroptical Correlation of Conformation, Tension, and Dynamics of DNA Self-Assembly.

Study of the conformational and mechanical behaviors of biomolecular assemblies is vital to the rational design and realization of artificial molecular architectures with biologically relevant functionality. Here, we revealed DNA-modulated and mechanoresponsive excitonic couplings between organic chromophores and verified strong correlations between the excitonic chiroptical responses and the conformational and mechanical states of DNA self-assemblies irrespective of fluorescence background interference. Besides, the excitonic chiroptical effect allowed sensitive monitoring of DNA self-assembled nanostructures due to small molecule bindings or DNA strand displacement reactions. Moreover, we developed a new chiroptical reporter, a DNA-templated dimer of an achiral cyanine5 and an intrinsically chiral BODIPY, that exhibited unique multiple-split spectral line shape of exciton-coupled circular dichroism, largely separated response wavelengths, and enhanced anisotropy dissymmetry factor (g-factor). These results shed light on a promising chiroptical spectroscopic tool for studying biomolecular recognition and binding, conformation dynamics, and soft mechanics in general.

Chicoric acid ameliorates LPS-induced inflammatory injury in bovine lamellar keratinocytes by modulating the TLR4/MAPK/NF-κB signaling pathway.

Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1ß, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P < 0.01), down-regulated the expression of TLR4, MyD88, p-ERK, p-p38, IKKß, p-p65, p-p50 (P < 0.05), and increased the IκBα protein expression (P < 0.05). In conclusion, Chicoric acid successfully protected cow lamellar keratinocytes from LPS-induced inflammatory responses by modulating the TLR4/MAPK/NF-κB signaling pathway and downregulating inflammatory mediators.

A HOOI-Based Fast Parameter Estimation Algorithm in UCA-UCFO Framework.

In this paper, we introduce a Reduced-Dimension Multiple-Signal Classification (RD-MUSIC) technique via Higher-Order Orthogonal Iteration (HOOI), which facilitates the estimation of the target range and angle for Frequency-Diverse Array Multiple-Input-Multiple-Output (FDA-MIMO) radars in the unfolded coprime array with unfolded coprime frequency offsets (UCA-UCFO) structure. The received signal undergoes tensor decomposition by the HOOI algorithm to get the core and factor matrices, then the 2D spectral function is built. The Lagrange multiplier method is used to obtain a one-dimensional spectral function, reducing complexity for estimating the direction of arrival (DOA). The vector of the transmitter is obtained by the partial derivatives of the Lagrangian function, and its rotational invariance facilitates target range estimation. The method demonstrates improved operation speed and decreased computational complexity with respect to the classic Higher-Order Singular-Value Decomposition (HOSVD) technique, and its effectiveness and superiority are confirmed by numerical simulations.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

[Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia].

OBJECTIVE: To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children. METHODS: The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared. RESULTS: A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011). CONCLUSIONS: The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.

A Fast Method for Multidimensional Joint Parameter Estimation of Polarization-Sensitive Arrays.

The paper proposes a fast method for the multidimensional parameter estimation of a polarization-sensitive array. Compared with conventional methods (e.g., MUSIC algorithm), the proposed method applies an iterative approach based on Newton's method to obtain joint estimation results instead of a spectral search and dimension reduction. It also extends the original Newton method to the 4D scale using the Hessian matrix. To reduce the complexity of establishing the aim function, Nystrom's method is applied to process the covariance matrix. A new threshold is also proposed to select the results, which can accomplish the parameter estimation with a small number of iterations while guaranteeing a high estimation accuracy. Finally, the proposed algorithm is analyzed in detail and the numerical simulations of various algorithms are compared to verify its effectiveness.

Reweighted Off-Grid Sparse Spectrum Fitting for DOA Estimation in Sensor Array with Unknown Mutual Coupling.

In the environment of unknown mutual coupling, many works on direction-of-arrival (DOA) estimation with sensor array are prone to performance degradation or even failure. Moreover, there are few literatures on off-grid direction finding using regularized sparse recovery technology. Therefore, the scenario of off-grid DOA estimation in sensor array with unknown mutual coupling is investigated, and then a reweighted off-grid Sparse Spectrum Fitting (Re-OGSpSF) approach is developed in this article. Inspired by the selection matrix, an undisturbed array output is formed to remove the unknown mutual coupling effect. Subsequently, a refined off-grid SpSF (OGSpSF) recovery model is structured by integrating the off-grid error term obtained from the first-order Taylor approximation of the higher-order term into the underlying on-grid sparse representation model. After that, a novel Re-OGSpSF framework is formulated to recover the sparse vectors, where a weighted matrix is developed by the MUSIC-like spectrum function to enhance the solution's sparsity. Ultimately, off-grid DOA estimation can be realized with the help of the recovered sparse vectors. Thanks to the off-grid representation and reweighted strategy, the proposed method can effectively and efficiently achieve high-precision continuous DOA estimation, making it favorable for real-time direction finding. The simulation results validate the superiority of the proposed method.

Silencing LCN2 enhances RSL3-induced ferroptosis in T cell acute lymphoblastic leukemia.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a life-threatening malignancy and therapeutic toxicity remains a huge challenge for survival rates. A novel iron-dependent form of cell death, ferroptosis, shows potentials in cancer therapy. This study aimed to identify ferroptosis-associated hub genes within a proteinprotein interaction (PPI) network. METHODS: We screened differential expressed genes (DEGs) in GSE46170 dataset and obtained ferroptosis-related genes from FerrDb database. Through overlapping between DEGs and ferroptosis-related genes, ferroptosis-associated DEGs were identified for further PPI network construction. Molecular complex detection (MCODE) algorithm in Cytoscape was employed to determine tightly connected protein clusters. Chord diagram of Gene Ontology (GO) was generated to reveal the potential biological process of hub genes. Through transfection with siRNA of lipocalin 2 (LCN2) into TALL cells, the regulatory role of LCN2 in ferroptosis was investigated. RESULTS: Venn diagram identified a total of 37 ferroptosis-associated DEGs between GSE46170 and ferroptosis-associated genes, which were mainly enriched in ferroptosis and necroptosis. Based on PPI network analysis, 5 hub genes (LCN2, LTF, HP, SLC40A1 and TFRC) were found. These hub genes were involved in iron ion transport and could distinguish T-ALL from normal individuals. Further experimental studies demonstrated that LCN2 was highly expressed in T-ALL, while silencing LCN2 promoted RSL3-induced ferroptotic cell death in T-ALL cells. CONCLUSION: This study identified novel ferroptosis-associated hub genes, which shed new insights into the underlying mechanism of ferroptosis in T-ALL and also provide promising therapeutic targets for T-ALL.

Mussel-inspired proteins functionalize catheter with antifouling and antibacterial properties.

Bacterial adhesion and subsequent biofilm formation on catheter can cause inevitably infection. The development of multifunctional antibacterial coating is a promising strategy to resist the bacteria adhesion and biofilm formation. Herein, a mussel-inspired chimeric protein MZAgP is prepared and employed to modify a variety of polymeric catheters. The MZAgP is composed of mussel-adhesive peptide, zwitterionic peptide, and silver-binding peptide, which can endow catheters with antifouling, bactericidal and biocompatibility performances. Expectedly, negligible biofilm is observed on the MZAgP coated catheters after incubating with bacteria for 120 h. And ignorable hemolysis and cytotoxicity are obtained on coated catheters. In addition, the modified catheters also display persistent antifouling and bacteriostatic properties throughout 168 h under hydrodynamic conditions. Moreover, the coated catheters can still remain excellent antifouling and antibacterial properties even after 2 months of storage. This multifunctional coating may be promising as antibacterial and antibiofilm biomaterial, and the coated catheters are potential in clinical application.

The combination of a prolonged treatment time window and alpha-fetoprotein benefits the tumor response of hepatocellular carcinoma patients as evaluated by the imRECIST: a single-center, retrospective study.

Background: The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. Methods: This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Results: Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). Conclusions: In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

Isolation and culture of lamellar keratinocyte from bovine hoof.

Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. In this study, we described four digestion methods: trypsin method, collagenase method, Dispase II combined with trypsin method, and Dispase II combined with collagenase method, compared their isolation and culture efficiency, observed primary cell and subculture cell growth, and according to the difference of digestion time and apposition time of fibroblasts and keratinocytes, lamellar keratinocytes were purified by differential digestion method as well as differential velocity adherent method at each passaging and identified specific keratin 14 of keratinocytes using immunofluorescence. The results revealed that the lamellar keratinocytes isolated using Dispase II combined with the collagenase method increased rapidly, the number of cells in the offspring 4 generation was high, and the cells demonstrated positive expression of keratin,which facilitated the subsequent purification.

A review of curcumin in food preservation: Delivery system and photosensitization.

As a natural polyphenol, curcumin has been used as an alternative to synthetic preservatives in food preservation. Different from previous reviews that mainly focus on the pH-responsive discoloration of curcumin to detect changes in food quality in real time, this paper focuses on the perspective of the delivery system and photosensitization of curcumin for food preservation. The delivery system is an effective means to overcome the challenges of curcumin like instability, hydrophobicity, and low bioavailability. Curcumin as a photosensitizer can effectively sterilize to preserve food. The practical fresh-keeping effects of the delivery system and photosensitization of curcumin on foods (fruits/vegetables, animal-derived food, and grain) were summarized comprehensively, including shelf-life extension, maintenance of physicochemical properties, nutritional quality, and sensory. Future research should focus on the development of novel curcumin-loaded materials used for food preservation, and most importantly, the biosafety and accumulation toxicity associated with these materials should be explored.