Process optimization for microfluidic preparation of liposomes using food-grade components.

This study explores the potential for optimizing a sustainable manufacturing process that maintains the essential characteristics of conventional liposomes using food-grade solvents and components. The focus was comparing the physicochemical, morphological, and interfacial properties of liposomes produced with these food-grade ingredients to those made by conventional methods. It was found that there was no significant difference in particle size (195.87 ± 1.40 nm) and ζ-potential (-45.13 ± 0.65 mV) between liposomes made from food-grade and conventional materials. The manufacturing process for liposomes, utilizing food-grade solvents and components, was optimized through the application of Plackett-Burman design and response surface methodology. This approach helped identify key parameters (soy lecithin, ß-sitosterol, W/O ratio) and their optimal values (3.17 g, 0.25 g, 1:2.59). These findings suggest that it is possible to enhance the use of liposomes as an effective and safe delivery system in the food industry, adhering to the strict guidelines set by regulatory agencies.

scINRB: single-cell gene expression imputation with network regularization and bulk RNA-seq data.

Single-cell RNA sequencing (scRNA-seq) facilitates the study of cell type heterogeneity and the construction of cell atlas. However, due to its limitations, many genes may be detected to have zero expressions, i.e. dropout events, leading to bias in downstream analyses and hindering the identification and characterization of cell types and cell functions. Although many imputation methods have been developed, their performances are generally lower than expected across different kinds and dimensions of data and application scenarios. Therefore, developing an accurate and robust single-cell gene expression data imputation method is still essential. Considering to maintain the original cell-cell and gene-gene correlations and leverage bulk RNA sequencing (bulk RNA-seq) data information, we propose scINRB, a single-cell gene expression imputation method with network regularization and bulk RNA-seq data. scINRB adopts network-regularized non-negative matrix factorization to ensure that the imputed data maintains the cell-cell and gene-gene similarities and also approaches the gene average expression calculated from bulk RNA-seq data. To evaluate the performance, we test scINRB on simulated and experimental datasets and compare it with other commonly used imputation methods. The results show that scINRB recovers gene expression accurately even in the case of high dropout rates and dimensions, preserves cell-cell and gene-gene similarities and improves various downstream analyses including visualization, clustering and trajectory inference.

Study on the Direct and Indirect Photolysis of Antibacterial Florfenicol in Water Using DFT/TDDFT Method and Comparison of Its Reactivity with Hydroxyl Radical under the Effect of Metal Ions.

Florfenicol (FLO) is a widely used antibacterial drug, which is often detected in the environment. In this paper, the photolysis mechanism of FLO in water was investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The focus of the study is to elucidate the direct photolysis mechanism of FLO in the water environment and the indirect photolysis of free radicals (·OH, ·NO3, and ·SO4-) as active species. The effect of metal ions Ca2+/Mg2+/Zn2+ on the indirect photolysis was also investigated. The results show that the direct photolysis of FLO involves C-C/C-N/C-S bond cleavage, the C5-S7 bond cleavage is most likely to occur, and the C17-C18 cleavage reaction is not easy to occur during the direct photodegradation of FLO. The indirect photolysis of FLO is more likely to occur in the environment than direct photolysis. The main indirect photolysis involves OH-addition, NO3-addition, and SO4-addition on benzene ring. The order of difficulty in the indirect photolysis with ·OH is C2 > C3 > C4 > C5 > C6 > C1, Ca2+ can promote the indirect photolysis with ·OH, and Mg2+/Zn2+ has a dual effect on the indirect photolysis with ·OH. In other words, Mg2+ and Zn2+ can inhibit or promote the indirect photolysis with ·OH. These studies provide important information for theoretical research on the environmental behavior and degradation mechanism of drug molecules.

Protein-enriched and anti-inflammatory dietary patterns, healthy lifestyle index and depressive symptoms: A cross-sectional study of 287,945 adults in China.

OBJECTIVES: Depressive symptoms have a considerable negative impact on mental health. This study aimed to understand the relationship between the protein-enriched and anti-inflammatory dietary index scores, modified healthy lifestyle index scores (Modified HLIS), and depressive symptoms. METHODS: This study used convenience sampling to conduct a single-center cross-sectional survey. From January 1, 2015 to December 31, 2020, a total of 287,945 Chinese adults from a health management center of a general hospital completed an online self-reported health questionnaire, which included demographic characteristics, the Dietary Diversity Scale, the Modified Healthy Lifestyle Index Scores and the Patient Health Questionnaire-9. RESULTS: The higher anti-inflammatory dietary index scores (POR = 0.87; 95 % CI: 0.86-0.87; p < 0.001), moderate modified healthy lifestyle index scores (POR = 0.76; 95 % CI: 0.75-0.78; p < 0.001) and sufficient modified healthy lifestyle index scores (POR = 0.53; 95 % CI: 0.52-0.54; p < 0.001) were negatively associated with depressive symptoms, while the higher protein-enriched dietary index scores (POR = 1.01; 95 % CI: 1.01-1.02; p < 0.001) was positively correlated with depressive symptoms. CONCLUSIONS: This study demonstrated that protein-enriched and anti-inflammatory dietary index scores, and multiple healthy lifestyles are associated depressive symptoms in adults.

Development of a human-size magnetic particle imaging device for sentinel lymph node biopsy of breast cancer.

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 kHz@1.5 mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 µg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 µg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.

Targeting tumor and bone microenvironment: Novel therapeutic opportunities for castration-resistant prostate cancer patients with bone metastasis.

Despite standard hormonal therapy that targets the androgen receptor (AR) attenuates prostate cancer (PCa) effectively in the initial stage, the tumor ultimately converts to castration-resistant prostate cancer (CRPC), and the acquired resistance is still a great challenge for the management of advanced prostate cancer patients. The tumor microenvironment (TME) consists of multiple cellular and noncellular agents is well known as a vital role during the development and progression of CRPC by establishing communication between TME and tumor cells. Additionally, as primary prostate cancer progresses towards metastasis, and CRPC always experiences bone metastasis, the TME is conducive to the spread of tumors to the distant sits, particularly in bone. In addition, the bone microenvironment (BME) is also closely related to the survival, growth and colonization of metastatic tumor cells. The present review summarized the recent studies which mainly focused on the role of TME or BME in the CRPC patients with bone metastasis, and discussed the underlying mechanisms, as well as the potential therapeutic values of targeting TME and BME in the management of metastatic CRPC patients.

Recent Progress in CDK4/6 Inhibitors and PROTACs.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.

Preparation of Lignin-Based Nanoparticles with Excellent Acidic Tolerance as Stabilizer for Pickering Emulsion.

In this work, novel lignin-based nanoparticles (LßNPs) with high acidic tolerance were successfully prepared via electrostatic interaction between ß-alanine and lignin nanoparticles. The effects of the mass ratio of lignin nanoparticles to ß-alanine and pH value on the morphology and particle sizes of LßNPs were investigated with the aim of obtaining the ideal nanoparticles. The optimized LßNPs were spherical in shape with an average particle size of 41.1 ± 14.5 nm and exhibited outstanding structure stability under high acidic conditions (pH < 4). Subsequently, Pickering emulsions stabilized by LßNPs were prepared using olive oil as the oil phase. Additionally, the effects of pH value, droplet size, morphology, and storage stability on Pickering emulsions were also analyzed. The emulsions displayed excellent stability, and were stable against strongly acidic conditions (pH < 4) after 30 days of storage. The study presented a promising approach to preparing lignin-based nanoparticles with high acidic tolerance (an ideal type of stabilizer to prepare emulsions), and exhibited extremely high potential application values in the fields of drug delivery, food additives, and oily wastewater treatment.

A Biodegradable High-Performance Microsupercapacitor for Environmentally Friendly and Biocompatible Energy Storage.

Biodegradable and biocompatible microscale energy storage devices are very crucial for environmentally friendly microelectronics and implantable medical applications. Herein, a biodegradable and biocompatible microsupercapacitor (BB-MSC) with satisfying overall performance is realized via the combination of three-dimensional (3D) printing technique and biodegradable materials. Due to the 3D-interconnected structure of electrodes and elaborated design of electrolyte, the as-prepared BB-MSC exhibits superior overall performance than most of biodegradable devices, including a wide operation voltage of 1.8 V, high areal specific capacitance of 251 mF/cm2, good cycle stability, and favorable low-temperature resistance (-20 °C), demonstrative of reliability and practicality of our devices even in frosty environments. Importantly, the smooth degradation has been realized for the BB-MSC after being buried in natural soil for ∼90 days, and its implantation does not affect the healthy status of SD rats. Therefore, this work explores avenues for the design and construction of environmentally friendly and biocompatible microscale energy storage devices.

Associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer.

PURPOSE: Serum cortisol and inflammatory markers may play a role in depression and anxiety, but little is known about whether various features of serum cortisol and inflammatory markers have different associations with depression and anxiety. This study examines the associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. METHODS: Sixty-four young women with gynecologic cancer, aged 15-39 years, were recruited in a tertiary general hospital and a tertiary hospital specializing in oncology in China from May to December 2021. The Hospital Anxiety and Depression Scale was used to evaluate depression and anxiety. Blood samples were taken at 8 am, 4 pm, and 10 pm on the same day to examine the various features (average, variability, and diurnal patterns) of serum cortisol and inflammatory markers, namely C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RESULTS: Young women with gynecologic cancer who reported depression/anxiety had significantly higher average levels of serum cortisol, IL-6 and TNF-α than those who did not. The dysregulations in the diurnal patterns of serum cortisol and IL-6 were associated with depression and anxiety. Serum cortisol levels were significantly higher in the depression/anxiety group at 10 pm. Depression and anxiety were associated with elevated levels of IL-6 and TNF-α at each time point. CONCLUSION: This study revealed various associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. Further research is needed to understand the role of serum cortisol and inflammatory marker features in the progression of depression and anxiety.

CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signaling pathway.

CD9 is a member of the tetraspanin protein family, which has been widely studied in inflammation and cancer, but not in pathological cardiac hypertrophy. In this study, we found that the expression of CD9 was increased in transaortic constriction (TAC) myocardial tissue. Knockdown of CD9 alleviated damage to cardiac function in the TAC model and reduced heart weight, cardiomyocyte size, and degree of fibrosis, and vice versa. Mechanistically, co-immunoprecipitation results showed that CD9 and GP130 can bind to each other in cardiomyocytes, and knockdown of CD9 can reduce the protein level of GP130 and the phosphorylation of STAT3 in vivo and in vitro, and vice versa. GP130 knockdown reversed the aggravating effects of CD9 on pathological cardiac hypertrophy. Therefore, we conclude that CD9 exacerbates pathological cardiac hypertrophy by regulating the GP130/STAT3 signaling pathway and may serve as a therapeutic target for pathological cardiac hypertrophy.

Evaluation of Molecular Simulations and Deep Learning Prediction of Antibodies' Recognition of TRBC1 and TRBC2.

T cell receptor ß-chain constant (TRBC) is a promising class of cancer targets consisting of two highly homologous proteins, TRBC1 and TRBC2. Developing targeted antibody therapeutics against TRBC1 or TRBC2 is expected to eradicate the malignant T cells and preserve half of the normal T cells. Recently, several antibody engineering strategies have been used to modulate the TRBC1 and TRBC2 specificity of antibodies. Here, we used molecular simulation and artificial intelligence methods to quantify the affinity difference in antibodies with various mutations for TRBC1 and TRBC2. The affinity of the existing mutants was verified by FEP calculations aided by the AI. We also performed long-time molecular dynamics simulations to reveal the dynamical antigen recognition mechanisms of the TRBC antibodies.

Phage SPO1 Protein Gp49 Is a Novel RNA Binding Protein That Is Involved in Host Iron Metabolism.

Bacillus subtilis is a model organism for studying Gram-positive bacteria and serves as a cell factory in the industry for enzyme and chemical production. Additionally, it functions as a probiotic in the gastrointestinal tract, modulating the gut microbiota. Its lytic phage SPO1 is also the most studied phage among the genus Okubovrius, including Bacillus phage SPO1 and Camphawk. One of the notable features of SPO1 is the existence of a "host-takeover module", a cluster of 24 genes which occupies most of the terminal redundancy. Some of the gene products from the module have been characterized, revealing their ability to disrupt host metabolism by inhibiting DNA replication, RNA transcription, cell division, and glycolysis. However, many of the gene products which share limited similarity to known proteins remain under researched. In this study, we highlight the involvement of Gp49, a gene product from the module, in host RNA binding and heme metabolism-no observation has been reported in other phages. Gp49 folds into a structure that does not resemble any protein in the database and has a new putative RNA binding motif. The transcriptome study reveals that Gp49 primarily upregulates host heme synthesis which captures cytosolic iron to facilitate phage development.

Influence of metabolic syndrome and lifestyle factors on thyroid nodules in Chinese adult men: a cross-sectional study.

Introduction: Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China. Methods: This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables. Results: The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules. Conclusion: The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.

Burden of Lung Cancer in China, 1990-2019: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.

Arbidol: The current demand, strategies, and antiviral mechanisms.

BACKGROUND: High morbidity and mortality of influenza virus infection have made it become one of the most lethal diseases threatening public health; the lack of drugs with strong antiviral activity against virus strains exacerbates the problem. METHODS: Two independent researchers searched relevant studies using Embase, PubMed, Web of Science, Google Scholar, and MEDLINE databases from its inception to December 2022. RESULTS: Based on the different antiviral mechanisms, current antiviral strategies can be mainly classified into virus-targeting approaches such as neuraminidase inhibitors, matrix protein 2 ion channel inhibitors, polymerase acidic protein inhibitors and other host-targeting antivirals. However, highly viral gene mutation has underscored the necessity of novel antiviral drug development. Arbidol (ARB) is a Russian-made indole-derivative small molecule licensed in Russia and China for the prevention and treatment of influenza and other respiratory viral infections. ARB also has inhibitory effects on many other viruses such as severe acute respiratory syndrome coronavirus 2, Coxsackie virus, respiratory syncytial virus, Hantaan virus, herpes simplex virus, and hepatitis B and C viruses. ARB is a promising drug which can not only exert activity against virus at different steps of virus replication cycle, but also directly target on hosts before infection to prevent virus invasion. CONCLUSION: ARB is a broad-spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high-quality clinical studies are required to establish the efficacy and safety of ARB.

Natural-Wood-Inspired Ultrastrong Anisotropic Hybrid Hydrogels Targeting Artificial Tendons or Ligaments.

Hydrogels are able to mimic the flexibility of biological tissues or skin, but they still cannot achieve satisfactory strength and toughness, greatly limiting their scope of application. Natural wood can offer inspiration for designing high-strength hydrogels attributed to its anisotropic structure. Herein, we propose an integrated strategy for efficient preparation of ultrastrong hydrogels using a salting-assisted prestretching treatment. The as-prepared poly(vinyl alcohol)/cellulose nanofiber hybrid hydrogels show distinct wood-like anisotropy, including oriented molecular fiber bundles and extended grain size, which endows materials with extraordinarily comprehensive mechanical properties of ultimate breaking strength exceeding 40 MPa, strain approaching 250%, and toughness exceeding 60 MJ·m-3, and outstanding tear resistance. Impressively, the breaking strength and toughness of the reswollen preoriented hydrogels approach 10 MPa and 25 MJ·m-3, respectively. In vitro and in vivo tests demonstrate that the reswollen hydrogels do not affect the growth and viability of the cells, nor do they cause the inflammation or rejection of the mouse tissue, implying extremely low biotoxicity and perfect histocompatibility, showcasing bright prospects for application in artificial ligaments or tendons. The strategy provided in this study can be generalized to a variety of biocompatible polymers for the fabrication of high-performance hydrogels with anisotropic structures.

Emergence of ST463 exoU-Positive, Imipenem-Nonsusceptible Pseudomonas aeruginosa Isolates in China.

This study investigated the resistance mechanisms and the distribution and proportions of virulence genes, including exoU, in 182 imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) strains collected from China in 2019. There was no obvious prevalent sequence type or concentrated evolutionary multilocus sequence typing (MLST) type on the INS-PA phylogenetic tree in China. All of the INS-PA isolates harbored ß-lactamases with/without other antimicrobial mechanisms, such as gross disruption of oprD and overexpression of efflux genes. Compared with exoU-negative isolates, exoU-positive isolates (25.3%, 46/182) presented higher virulence in A549 cell cytotoxicity assays. The southeast region of China had the highest proportion (52.2%, 24/46) of exoU-positive strains. The most frequent exoU-positive strains belonged to sequence type 463 (ST463) (23.9%, 11/46) and presented multiple resistance mechanisms and higher virulence in the Galleria mellonella infection model. The complex resistance mechanisms in INS-PA and the emergence of ST463 exoU-positive, multidrug-resistant P. aeruginosa strains in southeast China indicated a challenge that might lead to clinical treatment failure and higher mortality. IMPORTANCE This study investigates the resistance mechanisms and distribution and proportions of virulence genes of imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) isolates in China in 2019. Harboring PDC and OXA-50-like genes is discovered as the most prevalent resistance mechanism in INS-PA, and the virulence of exoU-positive INS-PA isolates was significantly higher than that of exoU-negative INS-PA isolates. There was an emergence of ST463 exoU-positive INS-PA isolates in Zhejiang, China, most of which presented multidrug resistance and hypervirulence.