Blood Calcium, Genetic Risk, and Risk of Incident Kidney Stone: A Population-Based Cohort Study.

OBJECTIVE: To investigate the association between blood calcium concentration and incident kidney stone as well as to assess the role played by genetic susceptibility. METHODS: We performed a population-based cohort study based on participants from the UK Biobank. A multivariable Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs of incident kidney stone for blood calcium level and polygenic risk score (PRS). In addition, the potential interaction was explored. The study was conducted from January 28, 2023, through June 4, 2023. RESULTS: During the follow-up of 423,301 participants with a total of 5,490,332 person-years (median follow-up of 13.4 years), 4502 cases of kidney stone were recorded. Compared with the low blood calcium concentration group (first tertile), individuals in the high (third tertile) and moderate (second tertile) concentration groups had higher risks of kidney stone with HRs of 1.24 (95% CI, 1.15 to 1.33) and 1.11 (1.04 to 1.20), respectively. The PRS for kidney stone contained 40 independent single-nucleotide polymorphisms and was used to assign individuals to 3 groups according to the quintile. Participants with high (Q5) and moderate (Q2 to Q4) genetic risks had increased risks of kidney stone compared with low (Q1) genetic risk with HRs of 1.70 (1.53 to 1.89) and 1.31 (1.20 to 1.44), respectively. There was a joint cumulative risk of incident kidney stone between blood calcium concentration and genetic susceptibility. CONCLUSIONS: Blood calcium concentration and PRS are significantly associated with incident kidney stone risk. Excessive blood calcium concentration might bring additional stone risk in populations at high genetic risk. A nonlinear correlation between blood calcium concentration and kidney stone risk was indicated.

Associations of prior pulmonary tuberculosis with the incident COPD: a prospective cohort study.

BACKGROUND: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. OBJECTIVES: This study aimed to investigate the association of prior PTB with the risk of COPD. DESIGN: Prospective cohort study. METHODS: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). RESULTS: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, p = 0.008), male with aHR of 2.37 (1.47-3.83, p < 0.001), obesity with aHR of 3.35 (2.16-5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, p < 0.001), current drinking with aHR of 1.98 (1.47-3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, p = 0.019). CONCLUSION: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Associations of prior pulmonary tuberculosis with the incident COPDPrior pulmonary tuberculosis (PTB) indicates that an individual has a history of PTB. The impact of prior PTB on the risk of incident chronic obstructive pulmonary disease (COPD) has not been studied in a large prospective cohort study of European population. Here, we investigated the association between prior PTB and risk of COPD in 216,130 participants from the UK biobank (a large biomedical database). After a median follow up of more than 12 years, 2,788 incident COPD cases were recorded. Individuals with prior PTB at baseline had an 87% higher risk of developing incident COPD compared to those without history of PTB. Specifically, individuals with prior PTB presented with a higher risk of incident COPD among those who were older than 50 years, male, obese, had a previous history of smoking, are currently drinking, have low physical activity, and have a low and high genetic predicted lung function. This study suggested prior PTB as an important and independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture.

Kidney stone disease (KSD) is a complex disorder with high heritability and prevalence. We performed a large genome-wide association study (GWAS) meta-analysis for KSD to date, including 720,199 individuals with 17,969 cases in European population. We identified 44 susceptibility loci, including 28 novel loci. Cell type-specific analysis pinpointed the proximal tubule as the most relevant cells where susceptibility variants might act through a tissue-specific fashion. By integrating kidney-specific omics data, we prioritized 223 genes which strengthened the importance of ion homeostasis, including calcium and magnesium in stone formation, and suggested potential target drugs for the treatment. The genitourinary and digestive diseases showed stronger genetic correlations with KSD. In this study, we generate an atlas of candidate genes, tissue and cell types involved in the formation of KSD. In addition, we provide potential drug targets for KSD treatment and insights into shared regulation with other diseases.

Oxidative Stress Effects of Multiple Pollutants in an Indoor Environment on Human Bronchial Epithelial Cells.

Benzene, toluene, and xylene (denoted as BTX) are normally used in coatings, sealants, curing agents and other home decoration products, which can cause harm to human health. However, traditional studies mostly focus on the toxicity evaluation of a single pollution source, and little attention has been paid to the toxicity reports of multiple pollutants in a complex system. To evaluate the impact of indoor BTX on human health at the cellular level, the oxidative stress effect of BTX on human bronchial epithelial cells was assessed, including cell cytotoxicity, intracellular ROS, cell mitochondrial membrane potential, cell apoptosis, and CYP2E1 expression. The concentrations of BTX introduced into the human bronchial epithelial cell culture medium were determined based on both the tested distribution in 143 newly decorated rooms and the limited concentrations in the indoor air quality (denoted as IAQ) standards. Our study showed that the concentration in line with the standard limit may still pose a serious risk to health. The cellular biology effect studies of BTX showed that BTX, even at concentrations lower than the national standard limit, can still induce observable oxidative stress effects which warrant attention.

Combining Ruthenium(II) Complexes with Metal-Organic Frameworks to Realize Effective Two-Photon Absorption for Singlet Oxygen Generation.

Singlet oxygen ((1)O2), as a reactive oxygen species, has garnered serious attention in physical, chemical, and biological studies. In this paper, we designed and synthesized a new type of singlet-oxygen generation system by exchanging cationic ruthenium complexes (RCs) into anionic bio-MOF-1. The resulting bio-MOF-1&RCs can be used as effective photocatalysts for generation of singlet oxygen under both single-photon and two-photon excitation. Especially, the excellent two-photon absorption (TPA) behavior of bio-MOF-1&RCs aroused our interest greatly because their two-photon absorption band lies in the optical window of biological tissue. Here, we measured the ability of bio-MOF-1&RCs to generate (1)O2 by irradiation under both 490 and 800 nm wavelength light in DMF. 1,3-Diphenylisobenzofuran (DPBF) and 2',7'-dichlorofluorescein (DCFH) were used as typical (1)O2 traps to detect and evaluate the efficiency of generation of (1)O2 under single-photon and two-photon excitation, respectively. Results indicated that bio-MOF-1&[Ru(phen)3](2+) was able to effectively generate (1)O2 under both conditions. Our work creates a novel synergistic TPA system with the excellent photophysical properties of RCs and the unique microporous structure benefit of MOFs, which may open a new avenue for creation of a cancer treatment system with both photodynamic therapy and chemotherapy.

Ratiometric fluorescent nanosensors for selective detecting cysteine with upconversion luminescence.

Fluorescent sensors based on upconversion (UC) luminescence have been considered as a promising strategy to detect bio-analyte due to their advantages in deep penetration, minimum autofluorescence, and ratiometric fluorescent output. A prototype of nanosensors combined with mesoporous silica coated upconversion nanoparticles (UCNPs) and a fluorescein-based fluorescent probe loaded in pores was therefore designed to detect cysteine (Cys). The silica shell provided loading space for the probe and enabled the nanosensors to disperse in water. In the presence of Cys, the fluorescent probe was transformed into 5(6)-carboxyfluorescein with an emission band centering at 518 nm which was secondarily excited by the light at around 475 nm from NaYF4:Yb(3+), Tm(3+) UCNPs driven by 980 nm near-infrared (NIR) laser. The intensity ratio between green and blue luminescence (I518/I475) grew exponentially with increasing concentrations of Cys over a range of 20-200 µmolL(-1). The response of the nanosensors towards Cys was recognizable with naked eyes by luminescence color change. Evidences suggest that these nanosensors are capable of sensing Cys in aqueous solution and distinguishing Cys from homocysteine (Hcy) with kinetically-controlled selectivity. The system was further employed to detect Cys in human serum and the result was in agreement with it tested by high performance liquid chromatography with acceptable recovery.