Ionizable lipid nanoparticles (LNP)-mediated siRNA delivery provides a promising technological platform for cancer gene therapy. Traditional cancer treatment methods primarily focus on directly killing tumor cells, but RNA interference-based siRNA therapy can regulate the expression of genes related to disease, representing a therapeutic strategy shifting from "killing tumors" to "regulating genes." LNP, as one of the most mature non-viral nucleic acid delivery systems currently available, relies on its adjustable lipid composition, good biosafety and pH-responsive charge-conversion capability, and is able to protect siRNA from acid-enzyme degradation, promote cellular uptake, and achieve endosomal escape. Therefore, it overcomes key delivery barriers, such as the poor in vivo stability and low cellular uptake efficiency of naked siRNA. The successful approval of Onpattro fully verified the possibility of clinical translation of the LNP-siRNA delivery platform. However, the current LNP system still has issues, such as insufficient tumor targeting, accumulation in non-target tissues, and difficulty in precisely regulating them in vivo behavior. To overcome the above bottlenecks, researchers have been continuously improving the active tumour-targeting ability and delivery precision of LNPs through methods such as surface functionalization and modification of lipid composition. First, the composition and structure of ionizable LNPs and their targeted delivery mechanism are introduced in this review. then, various targeted modification strategies for tumor siRNA delivery are systematically listed, including peptides, antibodies, amino acids, and receptor-ligand systems, and finally, the current challenges and future directions are summarized.

Although there have been some achievements in early detection and treatment, breast cancer is still a leading cause of cancer deaths among women worldwide. Due to differences in genes, signals, and how well they respond to treatment among the various types of breast cancer, there is frequently recurrence or resistance to therapy. The old candidate gene method and the RNAi screening method lack a priori knowledge and do not cover all gene interactions in the search for unknown gene regulatory factors. CRISPR-based functional genomics screening is a good way to study the functions of all the genes in the genome systematically. Both loss-of-function and gain-of-function types of CRISPR screening can be employed to find tumour-driving genes, drug-resistance factors and other good therapeutic targets. CRISPR has been applied to the screening of breast cancer in the discovery of driver genes, endocrine therapy resistance, chemotherapy resistance and other targeted therapy strategies. Problems and Future Directions of CRISPR Screening in Precision Medicine for Breast Cancer at Present are listed below.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease characterised by steatosis, inflammation, hepatocellular injury and fibrosis. Human liver organoid platforms offer a controllable system for modelling selected MASH-related processes and evaluating candidate therapeutics, but their performance varies across biological fidelity, pharmacological predictivity and translational readiness. This review evaluates three major platform types: pluripotent stem cell (PSC) - derived multicellular organoids, expandable hepatocyte organoids and assembled multicellular systems. Current evidence indicates that PSC-derived models provide the broadest representation of multicellular MASH phenotypes, hepatocyte organoids are particularly suitable for genetic and pharmacological screening, and assembled systems offer greater control over cell composition and experimental conditions. However, no single platform currently combines adult-like hepatic function, robust multicellular disease modelling, scalable screening and demonstrated clinical predictivity. Major limitations include immature cell states, donor and batch variability, and limited representation of perfusion, zonation and extrahepatic metabolism. Overall, liver organoids are best viewed as fit-for-purpose tools for mechanistic studies, target validation and early candidate evaluation, with future progress requiring improved standardisation, patient-tissue benchmarking and clinically relevant validation.

Diabetes remains a major public health problem in the United States, yet some adults who meet laboratory criteria have not received a diagnosis. Because screening usually occurs through contact with the healthcare system, insurance coverage and a usual source of care may influence whether diabetes is detected. This study examines healthcare access and diabetes detection among U.S. adults using the National Health and Nutrition Examination Survey (NHANES), August 2021-August 2023. The primary analysis classified diabetes using self-reported diagnosis and hemoglobin A1c and applied the NHANES phlebotomy weight, strata, and primary sampling units. Among 949 adults with diabetes in the complete-case regression sample, 149 were undiagnosed. After adjustment for age, sex, education, and body mass index, uninsured adults had 3.43 times higher adjusted odds of undiagnosed diabetes than insured adults (95% CI, 1.54-7.61; p = .006). Adults without a usual source of care had 2.75-fold higher adjusted odds than those who had one (95% CI, 1.28-5.92; p = .015). A fasting-subsample sensitivity analysis produced a similar insurance association. These findings indicate that limited healthcare access is associated with missed diabetes detection, although the cross-sectional design does not establish causation.

Fine particulate matter (PM 2.5 ) pollution poses severe threats to urban residents’ physical health. As a core manufacturing hub, Foshan generates massive air pollutant emissions and is under prominent pressure in air pollution prevention and control. Taking Foshan as the research object, this paper explores the seasonal distribution characteristics of urban PM 2.5 and corresponding pollution control measures. Literature analysis and case study are adopted as the main research methods. Spatially, PM 2.5 concentrations are higher in northern and central Foshan (Sanshui, Nanhai, Chancheng) and lower in the south (Shunde, Gaoming); temporally, concentrations peak in autumn and winter and reach minimum in summer, with an additional morning rush-hour peak (08:00–09:00) in diurnal cycles. The results show that PM 2.5 concentrations in Foshan present obvious seasonal variations, with higher pollution levels in winter. Manufacturing emissions act as the primary local pollution source. Targeted industrial regulation, joint regional prevention and vegetation optimization can effectively reduce PM 2.5 concentration and improve urban atmospheric environment quality.

Melanoma is a type of aggressive skin cancer that can become very difficult to treat, once it spreads beyond the original site. Surgery is the key to treat melanoma in its earlier stages, such as localized melanoma, and the melanoma has great potential to be successfully removed. On the other hand, once melanoma becomes advanced and enters the metastatic stage, it has historically resulted in limited treatment options as well as poor outcomes. This analysis combines findings from existing research and clinical trials to investigate how immune checkpoint inhibitors can be used for treating and early detection of advanced melanoma. Before the development of immune checkpoint inhibitors, existing treatments included chemotherapy and cytokine-based immunotherapies. Unfortunately, these past treatments produced limited responses and a small chance of leading to durable disease control. First, this paper explains the essential biological characteristics of melanoma, including its high number of mutations and its ability to evade the immune system, which contributes to melanoma progression. The next topic it elaborates on is how checkpoint inhibitors target two pathways that normally limit T-cell activity, which are PD-1 and CTLA-4. By applying checkpoint inhibitors, new drugs such as nivolumab, ipilimumab, and pembrolizumab, improves T-cells' ability to identify and target melanoma cells. Clinical evidence from major trials of ipilimumab, pembrolizumab, and nivolumab, shows improvements in overall survival, response rates, and long-term disease control compared with earlier treatments. While checkpoint inhibitors do not work for every patient and can cause significant immune-related side effects, they have made it possible for a large percentage of patients to survive from advanced melanoma.

Awareness of adipose tissue dysfunction as the underlying pathway for major metabolic diseases has been rising as research on inflammation and lipotoxicity makes progress. Adipose storage capacity is a tenuous boundary that results in surplus free fatty acids spilling into the circulation and deposit ectopically in the liver, skeletal muscle, and pancreas when surpassed. Existing pharmacological agents are efficient in accounting for downstream effects of lipid spillover but lack the capability of restoring the body's intrinsic lipid-buffering capacity, posing disease recurrence as a reverberating effect of these approaches. This paper proposes a novel therapeutic approach based on the concept of transplantation of autologous induced pluripotent stem cells (iPSC)-derived adipocytes as bioengineered lipid sinks that can intercept excess circulating lipids prior to ectopic disposition. This paper addresses the pathophysiologic basis of lipid spillover and lipotoxicity, discusses the current state of iPSC-to-adipocyte differentiation, presents the mechanistic rationale for this strategy and summarizes and critiques the translational barriers that remain from the development of this work toward preclinical validation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex course, and at present, only symptom management is available. Given that microtubule disassembly and neuronal toxicity caused by Tau hyperphosphorylation and aggregation are central to the onset and progression of AD, targeting the "Tau-microtubule axis" has become one of the main directions for the development of disease-modifying therapies (DMTs). This article systematically reviews the latest progress in intervention strategies targeting the Tau-microtubule axis according to the logical framework of "Tau pathogenic mechanisms—targeting Tau expression—inhibiting Tau aggregation—stabilizing microtubule structure—modulating EB1/EB3 dynamics and restoring their downstream repair programs". First, soluble oligomers (TauO) resulting from abnormal phosphorylation of the Tau protein can cause microtubule destabilization, synaptic toxicity and pathological spread, and exhibit synergistic toxicity with Aβ. Second, mRNA-level degradation (e.g., ASO drugs such as BIIB080 and AAV-miRNA) and immunotherapies can reduce pathological Tau expression at the source or peripherally; small-molecule inhibitors (e.g., LMTX and ACI-3024) can block the formation of toxic Tau aggregates. Third, microtubule stabilizers (e.g., Epothilone D, NAP) can restore the axonal transport network, and allosteric inhibitors (e.g., EBIN) can correct pathological calcium overload in the endoplasmic reticulum by blocking the abnormal binding of EB3 to IP3R3 and activate chromatin remodeling and repair programs. Single-target strategies have the problems of low blood-brain barrier permeability and limited intracellular target access. The following developments are expected to include high-precision biomarker screening (e.g., p-tau217, Tau-PET), new delivery vehicles, and combination therapies that target multiple links in the Tau-microtubule axis.

Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), known as a relatively aggressive type of breast cancer that is difficult to treat and has a high risk of early recurrence. Systemic therapy for this is generally cytotoxic chemotherapy. Paclitaxel (Taxol) and gemcitabine (GT regimen) have been selected as one of the standard options worldwide. However, the clinical medical community in China has found that the disease affects young premenopausal women more severely and has different mutation spectra. This paper will examine the pharmacology of the GT regimen. First, it will study the molecular structure and physical-chemical properties of paclitaxel and gemcitabine. The clinical delivery strategy will also be discussed. The traditional 21-day intermittent schedule has certain deficiencies, such as dose-limiting toxicity, acquired resistance and suboptimal biodistribution. Last but not the least, given the genetic and clinical differences between Western and Asian TNBC populations, Chinese-specific real-world data are in urgent need. Finally, we put forward three future directions to address the existing bottlenecks: (1) adjunct therapies for synergistic sensitisation and toxicity alleviation, (2) advanced drug delivery systems, (3) genotype-guided patient stratification.

Winter chilling is required for the vernalization of several spring-flowering bulbous plants, such as tulips, narcissi, and hyacinths, enabling them to complete floral induction within their bulbs before spring and produce normal blooms upon its arrival. However,because mean global temperatures are continuing to rise, fewer cumulative hours of sufficiently low winter chill are available today in many parts of the world where these bulbs traditionally thrived. Hence, concern arises over insufficient vernalization, delayed or irregular flowering, and the resulting poor ornamental quality should this problem persist. With respect to the current state of research, this article reviews recent studies on the relationship among climate change, plant phenology, and vernalization, examines current changes in the chilling requirements of spring-flowering bulbs under warmer winters, and evaluates the feasibility of the cultivation methods, conservation approaches, and breeding programs currently recommended as solutions, drawing on findings from these studies. It appears that adjusting growing conditions according to weather forecasts and selecting varieties with lower demands for cold treatment in winter will probably work best among all existing options for ensuring continued availability of bulbs for cut flowers under future scenarios involving more extreme warming of winter seasons, even though scientific evidence regarding certain kinds of ornamental geophytes still requires further study for the time being.