全部最新文献

The immunomodulatory potential of radiotherapy provides a strong rationale for its combination with immunotherapies and other immunostimulatory agents. However, current combinations yield suboptimal clinical benefits. As the mechanisms behind radiotherapy-induced immunomodulation are gradually unraveled, various key factors have been identified as critical modulators of this process, opening new possibilities for adapting radiotherapy to immunotherapy. Here, we discuss seven factors: dose‒fractionation regimens of radiotherapy (RT), sequence and timing of RT and immunotherapy, radiation field, type of ionizing radiation, normal tissue effects, choice of the lesion to irradiate and identification of biomarkers. Preclinical and clinical studies on the combination of immunotherapy and radiotherapy are discussed, novel immunotherapeutic approaches are highlighted and improvements in study design are suggested.

Rising global temperatures and heatwaves pose major health risks, particularly for pregnant women, infants and other vulnerable groups. Using Photovoice, we aimed to foreground how pregnant and postpartum women in an urban township in Tshwane, South Africa, experience and cope with heat stress. Fourteen women participated in two structured workshops held during the hot season (December 2023-January 2024). The first included reflective discussions on coping with heat and basic photography training. Over two weeks, participants captured over 300 images using disposable cameras or mobile phones. Selected images were reviewed and discussed in the second workshop. Thematic analysis of photographs and workshop transcripts identified three key themes: health impacts, coping strategies and structural challenges. Women preferred staying home on very hot days, where they had greater control over their environment. However, they struggled to soothe overheated infants, which they found distressing. They used simple cooling methods such as bathing or wet cloths but faced constraints including heat-trapping housing materials, inadequate ventilation, and limited access to water and electricity. These challenges led to a state of "un-coping"-where adaptation efforts are insufficient or counterproductive. Viewed through the women's "lens", these findings highlight the need for targeted adaptation strategies to improve climate resilience.

Background: Endometriosis (EMs) is a common gynecological disorder associated with infertility. EMs patients often require assisted reproductive technology (ART) but exhibit lower success rates. This study aimed to characterize the follicular fluid microbiome in EMs patients undergoing in vitro fertilization (IVF) and provide insights into mechanisms underlying lower pregnancy rates.

Methods: Follicular fluid samples were collected from EMs patients and control subjectsundergoing IVF. Microbial DNA was subjected to 16S rRNA gene sequencing. Bioinformatic analyses, including alpha and beta diversity analysis, microbial composition profiling and biomarker identification, were performed.

Results: The follicular fluid microbiome in EMs patients exhibited altered alpha and beta diversity compared to controls. Distinct microbial compositions were observed at various taxonomic levels. Differentially abundant taxa were identified as potential biomarkers for EMs. Microbial profiles were associated with clinical parameters such as oocyte quality and fertilization rates. Models based on microbial profiles were constructed to elucidate the relationship between EMs and IVF outcomes. Functional predictions suggested alterations in metabolic pathways in the follicular fluid microbiome of EMs patients.

Conclusions: This study revealed significant alterations in the follicular fluid microbiome of EMs patients, providing a basis for further research into the role of the microbiome in EMs-related infertility.

Artocarpus altilis methanolic extract (AAM) exhibits potent protective effects against particulate matter (PM)-induced skin damage; however, its poor aqueous solubility and limited skin permeability restrict its topical bioavailability. To overcome these limitations, we developed a polymer-based drug delivery system by fabricating electrospun nanofibers composed of polyvinylpyrrolidone (PVP), hydroxypropyl-β-cyclodextrin (HPBCD), and AAM. The optimized formulation engineering strategy enhanced AAM solubility via increased surface area, reduced crystallinity, and hydrogen bonding interactions with HPBCD/PVP. The nanofiber matrix also provided an occlusive effect, improving skin hydration and facilitating transdermal diffusion through the stratum corneum. In vitro studies demonstrated improved cellular uptake, greater permeability, and enhanced antioxidant activity, leading to superior anti-pollution efficacy compared to raw AAM in a PM-induced HaCaT keratinocyte model. These results highlight AAM-loaded electrospun nanofibers (ANFs) as a biodegradable, and environmentally sustainable platform for delivering plant-derived bioactive ingredient, offering high potential for advanced topical formulations targeting pollution-induced skin aging.

The incidence of prostate cancer continues to increase, making it the second most common malignant tumor among men worldwide. Immunotherapy has emerged as a key therapeutic strategy for treating tumors. Numerous studies have established that the efficacy of tumor immunotherapy is closely associated with the tumor microenvironment and T cell subsets. However, the specific functions of certain T cell subsets in prostate cancer remain incompletely characterized. Therefore, this study aimed to systematically investigate the distribution patterns of T cell subsets within the tumor microenvironment of prostate cancer patients and their correlations with clinicopathological parameters. Therefore, we investigated the impact of T cells on the tumor microenvironment of prostate cancer at the single-cell level. We employed a variety of analytical methods to reveal the functions of T cells, including cell interaction analysis, time-series analysis, enrichment analysis, immune infiltration analysis, and other analytical approaches. By integrating bulk RNA-seq data, we constructed and validated a prognostic risk model based on T cell marker genes. Finally, we utilized the ssGSEA and ESTIMATE algorithms to explore the relationship between the prognostic risk model and immunotherapy. After quality control, 16,999 cells from the single-cell data were retained for downstream analysis. Our study focused on T cells, revealing the communication between various cell types and T cells. Pseudotime analysis showed that different T cell marker genes exhibited differential expression at various time points, corresponding to distinct biological processes. Enrichment analysis indicated that T cell marker genes were enriched in several immune-related pathways. From our analysis, BCAS2, EIF2S2, RIOK3, and ATP6V1E1 were ultimately identified as prognostic markers. Immune infiltration analysis revealed that high-risk patients had lower immune scores, stromal scores, and ESTIMATE scores and greater tumor purity compared to low-risk patients. We analyzed the mechanisms involving T cells in prostate cancer from multiple perspectives, constructed a prognostic model, and conducted immune infiltration analysis. Our findings contribute to the understanding of prostate cancer and its prognosis, providing valuable insights for future research and prognostic assessments in prostate cancer.

Objectives: Migrant Domestic Workers (MDWs) face adverse living and working conditions that place them at a heightened risk of poor mental health outcomes. While prior research has examined MDWs' coping strategies and resilience, little is known about how they understand and engage in self-compassion, an intrapersonal process strongly linked to mental well-being. This study aimed to examine how MDWs conceptualize self-compassion and the sociocultural factors that influence their capacity to practice it.

Methods: Semi-structured interviews were conducted with ten female Filipino and Indonesian MDWs living in Singapore recruited through purposive and snowball sampling. Data were analyzed using reflexive thematic analysis.

Results: Three interrelated themes were generated: (1) grounding self-compassion in self-worth and identity, (2) contextual conditions shaping self-compassion, and (3) enacting self-compassion in everyday life. These themes illustrate the complex interplay between participants' internalized self-perceptions, cultural narratives, and structural conditions that shape their engagement with self-compassion.

Conclusions: The findings contribute to a more nuanced understanding of self-compassion in marginalized caregiving populations. They advocate for the need to address structural determinants of MDWs' well-being and to develop culturally sensitive psychoeducation and interventions.

Background: Malignant hypertension (mHTN) is a severe hypertensive emergency, often associated with renal deterioration. Kidney length may be of useful to identify patients with renal dysfunction. Whether kidney length in mHTN patients is associated with renal prognosis is unclear.

Methods: The study enrolled 280 mHTN patients with renal thrombotic microangiopathy (TMA) who underwent renal biopsy between 2008 and 2023. Linear regression was used to explore patient characteristics of kidney length. The association between kidney length and ≥15% increase in estimated glomerular filtration rate (eGFR), and end-stage renal disease (ESRD) was analyzed using Cox regression and logistic regression, respectively. Kidney length was analyzed in tertiles, using the first tertile as reference.

Results: Patients with larger kidney length had higher levels of body mass index (BMI) and eGFR, but lower levels of urea nitrogen, serum creatinine, uric acid, global sclerosis ratio, and tubular atrophy/interstitial fibrosis ratio. Kidney length was strongly positively correlated with BMI, and negatively related to tubular atrophy/interstitial fibrosis ratio. During the follow-up, 72 patients experienced a ≥15% increase in eGFR and 172 patients progressed to ESRD. Patients in the third tertile of kidney length had a better renal recovery outcome of ≥15% increase in eGFR and lower odds of ESRD.

Conclusions: In mHTN patients with renal TMA, large kidney length is associated with better renal function improvement of ≥15% increase in eGFR, and lower risk of ESRD. In clinical practice, the measurement of kidney length may serve as a non-invasive indicator to assess renal prognosis and inform timely treatment interventions in mHTN patients.

Anecdotal reports highlight increased methamphetamine, cocaine, and codeine-cough syrup use in Zimbabwe, with no clear empirical basis. Therefore, the scoping review aimed to identify primary evidence of patterns, harms and responses to substance use (SU) within Zimbabwe. Arksey and O'Malley's (2005) framework and the PRISMA Extension for Scoping Reviews (Tricco et al., 2018) were followed. Medline (Pub Med), Scopus, Academic Search Premier, Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus), African Index Medicus, Africa-Wide Information, Web of Science, PsycInfo, PsycArticles, and Web of Science conference proceedings were searched. 27 studies published between 2012, and February 2025 met the inclusion criteria and were synthesized using combined inductive-deductive thematic analysis. Patterns of SU included a wide range of drugs (e.g. alcohol, tobacco, cannabis, inhalants, codeine-cough syrups), with emergent literature on methamphetamine, cocaine and heroin. Socio-demographic patterns elucidated vulnerable groups (e.g. children living on the streets), and concentration of SU in high density urban areas. SU harms predominantly centered on the link to the HIV epidemic, whilst clinical and health responses to SU were significantly limited. SU should therefore be treated as a public health priority in Zimbabwe, and research capacity building is urgently required to address significant literature gaps.

Heterologous boosting with aerosolized or intramuscular Ad5-nCoV following a two-dose CoronaVac prime has been shown to induce higher antibody levels than a homologous CoronaVac booster. However, no specific modeling has been reported to characterize the kinetics of antibody waning for these heterologous regimens. By integrating longitudinal serological data from three randomized trials conducted in Jiangsu, China (NCT04892459, NCT04952727, NCT05043259), we applied linear mixed-effects models to establish both exponential and power-law decay models for neutralizing antibodies, including live-virus neutralizing antibodies against the prototype, Delta, and Omicron BA.1 variants, and pseudovirus neutralizing antibodies against Omicron BA.4/5 variant, respectively. The findings showed that the power-law model exhibited a superior fit over the exponential model across all antibody types (all ΔAICc < 0). According to the power-law model (at day 90), the half-lives of live-virus neutralizing antibodies against the wild-type SRAS-CoV-2 strain was 195 d (95% CI: 185-210) in the aerosolized Ad5-nCoV group, 226 d (220-252) in the intramuscular Ad5-nCoV group, versus 230 d (95% CI: 222-257) in the three-dose CoronaVac group. For the Omicron BA.1 variant, the half-life was 314 d (248-453) in the aerosolized Ad5-nCoV group, 168 d (159-180) in the intramuscular Ad5-nCoV group, compared to 196 d (174-230) in the three-dose CoronaVac group. Our model indicated that the heterologous booster with Ad5-nCoV after two-dose CoronaVac, particularly the aerosolized Ad5-nCoV, induces longer-lasting neutralizing antibodies than three-dose CoronaVac, preferably characterized by power-law decay models.