Current developments of gene therapy in human diseases.

Gene therapy has witnessed substantial advancements in recent years, becoming a constructive tactic for treating various human diseases. This review presents a comprehensive overview of these developments, with a focus on their diverse applications in different disease contexts. It explores the evolution of gene delivery systems, encompassing viral (like adeno-associated virus; AAV) and nonviral approaches, and evaluates their inherent strengths and limitations. Moreover, the review delves into the progress made in targeting specific tissues and cell types, spanning the eye, liver, muscles, and central nervous system, among others, using these gene technologies. This targeted approach is crucial in addressing a broad spectrum of genetic disorders, such as inherited lysosomal storage diseases, neurodegenerative disorders, and cardiovascular diseases. Recent clinical trials and successful outcomes in gene therapy, particularly those involving AAV and the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins, are highlighted, illuminating the transformative potentials of this approach in disease treatment. The review summarizes the current status of gene therapy, its prospects, and its capacity to significantly ameliorate patient outcomes and quality of life. By offering comprehensive analysis, this review provides invaluable insights for researchers, clinicians, and stakeholders, enriching the ongoing discourse on the trajectory of disease treatment.

Increasing levels of fishmeal replacement by defatted black soldier fly larvae meal reduced growth performance without affecting fillet quality in largemouth bass (Micropterus salmoides).

A 90-day feeding trial was conducted to evaluate the effects of replacing dietary fishmeal (FM) with defatted black soldier fly larvae meal (BSFL) on the growth performance and fillet quality of largemouth bass (Micropterus salmoides). The largemouth bass was divided into six groups (BSFL0, BSFL15, BSFL30, BSFL45, BSFL75, and BSFL100) and fed six isonitrogenous(CP 50%, 508 g/kg) and isolipid (CL 9%, 124 g/kg) diets, in which 0, 15%, 30%, 45%, 75%, and 100% of the fishmeal was replaced with BSFL, respectively. The results showed that the final body weight (FBW) and specific growth rate (SGR) of the largemouth bass decreased with increasing BSFL content, and they were significantly lower in BSFL75 than in BSFL0. The weight gain rate (WGR) decreased with increasing BSFL content and the feed conversion ratio (FCR) of largemouth bass increased with increasing BSFL content. The saturated fatty acids (SFAs) and n-3 polyunsaturated fatty acids (PUFA) contents of the largemouth bass fillet significantly decreased, and the n-6 PUFA content of the largemouth bass fillets significantly increased with increasing dietary BSFL. The fillet b* significantly decreased with increasing BSFL content. The biological parameters, fillet proximate nutrient composition, fillet amino acid composition, skin color, and fillet texture of the largemouth bass were not affected by the replacement of BSFL. Transcriptomic analysis revealed that BSFL replacement of FM affects the immune system and metabolic processes of largemouth bass through signaling pathways such as complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, and fat digestion and absorption. In conclusion, a replacement level lower than 45% BSFL was suggested for the overall growth and fillet quality of largemouth bass.

Comparative Study of the Structure and Height of CH4 Laminar Diffusion Flames: Effects of Fuel-Side versus Air-Side Dilution.

The strategy for introducing diluents is a critical practical concern in diluted combustion; however, a comprehensive understanding of the effects of fuel-side dilution versus air-side dilution is currently lacking. This numerical investigation systematically studied the effects of dilution strategies on methane coflow diffusion flames, with a focus on the flame structure and flame length. Common additives in practical combustion, specifically H2O and CO2, were introduced to either the fuel or the air streams, with dilution ratios (Z) ranging from 0 to 0.2, and the impacts of four dilution strategies were quantified and ranked. Detailed simulations were conducted using a well-validated two-dimensional (2D) flame code to gain a deep understanding of OH formation, flame attachment, temperature of the burner nozzle, and flame height. Systematic analyses in terms of heat transfer, molecular diffusion, and chemical kinetics were conducted. Results demonstrate that introducing diluents into the air stream exerts a more profound influence on suppressing OH formation compared with fuel-side dilution. Moreover, air-side dilution has a negligible influence on flame attachment, while increasing Z on fuel side significantly inhibits flame attachment, and the latter behavior is attributed to the diminished mass diffusion of CH4 toward the oxidizer side. As the flame attachment weakens, it causes a consequential reduction in heat transfer from the flame base to the burner. Accordingly, the nozzle temperature exhibits a more remarkable decrease with the fuel-side dilution ratio than with the air-side dilution ratio. Simultaneously, a more profound influence of Z on flame length was observed for fuel-side dilution than for air-side dilution, and the underlying mechanisms governing these two distinct dilution strategies were theoretically elucidated.

Identification of glycogene-based prognostic signature and validation of B3GNT7 as a potential biomarker and therapeutic target in breast cancer.

BACKGROUND: Breast cancer is the most common cancer worldwide, with the fifth highest mortality rate among all cancers and high risk of metastasis. However, potential biomarkers and molecular mechanisms underlying the stratification of breast cancer in terms of clinical outcomes remain to be investigated. Therefore, we aimed to find a novel prognostic biomarker and therapeutic target for breast cancer patients. METHODS: Unsupervised hierarchical clustering was used to perform comprehensive transcriptomic study of total 185 glycogenes in public datasets of breast cancer with clinicopathological and survival information. A glycogene-based signature for subtype classification was discovered using Limma packages, and relevance to four known molecular features was identified by GSVA. Experimental verification was performed and biological functions of B3GNT7 were characterized by quantitative RT-PCR, western blot, transwell assays, and lectin immunofluorescence staining in breast cancer cells. RESULTS: A 23-glycogene signature was identified for the classification of breast cancer. Among the 23 glycogenes, B3GNTs showed significantly positive associations with ER-/Her2- subtype in breast cancer patients (n = 2655). Overexpressed B3GNT7 were correlated with poor prognosis in breast cancer patients based on public datasets. B3GNT7 depletion inhibited cell proliferation, migration, and invasion, and decreased global fucosylation in MDA-MB-231 and HCC1937 breast cancer cells. CONCLUSIONS: Herein, we discovered a unique 23-gene signature for breast cancer patient glycogene-type classification. Among these genes, B3GNT7 was shown to be a potential biomarker for unfavorable outcomes and therapeutic target of breast cancer.

Resilience-enhancing interventions for family caregivers: A systematic review.

OBJECTIVES: To synthesize interventions designed to enhance resilience in family caregivers (FCs). METHODS: Electronic databases including PubMed, CINAHL, PsycINFO, and Scopus, were searched using index and keyword methods for articles published before January 2020. The review process followed the PRISMA review guidelines. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Six studies (seven articles) were included in this review. Quantitative evidence supports the benefits of psychoeducation, mindfulness-based intervention, and cognitive behavioral therapy (CBT)-based intervention but not expressive writing in improving in FCs' resilience. Four of the six included studies were randomized controlled trials. All included studies only met 40% to 60% of the MMAT criteria, indicating low to moderate levels of study quality. CONCLUSION: This review showed emerging evidence that psychoeducation, mindfulness-based intervention, and CBT-based intervention may improve caregiver resilience. However, it remains unclear which intervention and what dosage is the most effective in promoting FCs' resilience. Due to the small number of relevant studies and a low-to-moderate level of overall study quality, more rigorous clinical trials are needed to strengthen the current limited evidence base for FC resilience interventions.

Study on the In Silico Screening and Characterization, Inhibition Mechanisms, Zinc-Chelate Activity, and Stability of ACE-Inhibitory Peptides Identified in Naked Oat Bran Albumin Hydrolysates.

In this study, naked oat bran albumin hydrolysates (NOBAH) were subjected to gel chromatography with Sephadex G-15, reverse phase-high liquid performance separation, and UPLC-ESI-MS/MS identification. Six safe peptides including Gly-Thr-Thr-Gly-Gly-Met-Gly-Thr (GTTGGMGT), Gln-Tyr-Val-Pro-Phe (QYVPF), Gly-Ala-Ala-Ala-Ala-Leu-Val (GAAAALV), Gly-Tyr-His-Gly-His (GYHGH), Gly-Leu-Arg-Ala-Ala-Ala-Ala-Ala-Ala-Glu-Gly-Gly (GLRAAAAAAEGG), and Pro-Ser-Ser-Pro-Pro-Ser (PSSPPS) were identified. Next, in silico screening demonstrated that QYVPF and GYHGH had both angiotensin-I-converting enzyme (ACE) inhibition activity (IC50: 243.36 and 321.94 µmol/L, respectively) and Zinc-chelating ability (14.85 and 0.32 mg/g, respectively). The inhibition kinetics demonstrated that QYVPF and GYHGH were both uncompetitive inhibitors of ACE. Molecular docking showed that QYVPF and GYHGH could bind, respectively, three and five active residues of ACE with short hydrogen bonds (but not belonging to any central pocket). QYVPF and GYHGH could bind, respectively, twenty-two and eleven residues through hydrophobic interactions. Moreover, GYHGH was able to affect zinc tetrahedral coordination in ACE by interacting with His383. The inhibition activities of QYVPF and GYHGH toward ACE were relatively resistant to gastrointestinal digestion. GYHGH improved zinc solubility in the intestines (p > 0.05) because its amino and carboxyl groups were chelating sites for zinc ions. These results suggest the potential applications of naked oat peptides for potential antihypertension or zinc fortification.

Comparison of temporomandibular joint disc, meniscus, and intervertebral disc in fundamental characteristics and tissue engineering.

The temporomandibular joint (TMJ) disc, meniscus and intervertebral disc (IVD) are three fibrocartilage discs, which play critical roles in our daily life. Their degeneration contributes to diseases such as TMJ disorders, osteoarthritis and degenerative disc disease, affecting patients' quality of life and causing substantial morbidity and mortality. Interestingly, similar in some aspects of fundamental characteristics, they exhibit differences in other aspects such as biomechanical properties. Highlighting these similarities and differences can not only benefit a comprehensive understanding of them and their pathology but also assist in future research of tissue engineering. Likewise, comparing their tissue engineering in cell sources, scaffold and stimuli can guide imitation and improvement of their engineered discs. However, the anatomical structure, function, and biomechanical characteristics of the IVD, TMJ, and Meniscus have not been compared in any meaningful depth needed to advance current tissue engineering research on these joints, resulting in incomplete understanding of them and their pathology and ultimately limiting future research of tissue engineering. This review, for the first time, comprehensively compares three fibrocartilage discs in those aspects to cast light on their similarities and differences.

Cyanine-Functionalized 2,2'-Bipyridine Compounds for Photocatalytic Cancer Therapy.

Recently, interest has been given to developing photocatalytic anticancer drugs. This area of research is dominated by metal complexes. Here, we report the potential of lysosome/mitochondria targeting cyanine appended bipyridine compounds as the organic photocatalytic anticancer agents. The organocatalyst (bpyPCN) not only exhibits light-induced NADH oxidation but also generates intracellular ROS to demonstrate anticancer activity. This is the first example of organic compound induced catalytic NADH photo-oxidation in an aqueous solution and in cancer cells.

Photocatalytic glucose-appended bio-compatible Ir(III) anticancer complexes.

Rationally-designed glucose-appended Ir(III) photo-catalysts ([Ir(N,C)2(N,N-Glc)]+, Ir1-Ir3) show visible light-induced catalytic NAD(P)H oxidation in aqueous solution. The highly in vivo biocompatible complex, Ir3, shows lysosome and mitochondria targeting necro-apoptotic photo-cytotoxicity against various cancer cell lines and multicellular spheroids, while remaining non-toxic in the dark.

Single-Cell Quantification of a Highly Biocompatible Dinuclear Iridium(III) Complex for Photocatalytic Cancer Therapy.

Quantifying the content of metal-based anticancer drugs within single cancer cells remains a challenge. Here, we used single-cell inductively coupled plasma mass spectrometry to study the uptake and retention of mononuclear (Ir1) and dinuclear (Ir2) IrIII photoredox catalysts. This method allowed rapid and precise quantification of the drug in individual cancer cells. Importantly, Ir2 showed a significant synergism but not an additive effect for NAD(P)H photocatalytic oxidation. The lysosome-targeting Ir2 showed low dark toxicity in vitro and in vivo. Ir2 exhibited high photocatalytic therapeutic efficiency at 525 nm with an excellent photo-index in vitro and in tumor-bearing mice model. Interestingly, the photocatalytic anticancer profile of the dinuclear Ir2 was much better than the mononuclear Ir1, indicating for the first time that dinuclear metal-based photocatalysts can be applied for photocatalytic anticancer treatment.

In-vitro and In-vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts.

Photocatalytic anticancer profile of a IrIII photocatalyst (Ir3) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported. Ir3 showed selective photo-cytotoxicity against cisplatin- and sorafenib-resistant cell lines while remaining dormant to normal cell lines in the dark. Ir3 exhibited excellent photo-catalytic oxidation of cellular co-enzyme, the reduced nicotinamide adenine dinucleotide phosphate (NADPH), and amino acids via a single electron transfer mechanism. The photo-induced intracellular redox imbalance and change in mitochondrial membrane potential resulted in necrosis and apoptosis of cancer cells. Importantly, Ir3 exhibited high biocompatibility and photo-catalytic anticancer efficiency as evident from in vivo zebrafish and mouse cancer models. To the best of our knowledge, Ir3 is the first IrIII based photocatalyst with such a high biocompatibility and photocatalytic anticancer therapeutic effect.

Release of Sulfur and Nitrogen during Co-pyrolysis of Coal and Biomass under Inert Atmosphere.

Coal combustion is a major energy provider but also a serious pollutant emitter worldwide. Biomass has attracted increasing research attention due to its carbon neutral and other advantages during co-pyrolysis of coal. Therefore, pyrolysis of corn straw, lignite coal, and their mixed fuel was investigated using a horizontal tube furnace at a temperature range of 300-900 °C in this study by concentrating on emissions of nitrogen- and sulfur-bearing gases. Emissions of HCN, NH3, COS, and SO2 were monitored, and char yield was calculated during pyrolysis. Results showed that char yield decreases with increasing temperature due to the decomposition of heterocyclic aromatic hydrocarbon. Sulfur (42.45 wt %, 900 °C) and nitrogen (73.23 wt %, 600 °C) were released from the mixed fuel during pyrolysis. The synergistic effect between corn straw and coal was evaluated and their experimental and calculated values were compared. The synergistic effect on emissions was remarkable at a temperature range of 600-800 °C due to high biomass content and desynchronization of volatile matter emissions between the coal and biomass. Volatiles in the biomass, which are released before coal, stimulated the volatilization of coal. Several conventional gases, such as CH4 and C2H6, were also analyzed to investigate emission patterns at different temperatures.

[A study of cytomegalovirus (CMV) glycoprotein B genotypes in patients with CMV infection after hematopoietic stem cell transplantation].

OBJECTIVE: To study the different cytomegalovirus (CMV) glycoprotein (G) B genotypes in the patients with CMV infection after hematopoietic stem cell transplantation (HSCT) and the correlation between genotype and pathogenesis of CMV disease. METHODS: Thirty-eight patients received allogenetic from March 2001 to December 2003. CMV GB DNA was detected with nested-PCR in all the patients and the products were digested with RsaI and HinfI. RESULTS: The distribution of GB types were as follows: GB1, 19/38 (50.0%); GB2, 3/38 (7.9%), GB3, 14/38 (36.8%). GB1 was associated with favorable clinical outcome, while GB3 might contribute to fatal interstitial pneumonia (IP). The incidences of graft versus host disease (GVHD) were not different significantly between the patients with GB1 and those with GB3. CONCLUSION: CMV GB genotypes might play an important role in the pathogenesis of CMV-IP, but not of GVHD.