Switching indoor fuels and the incidence of physical-psychological-cognitive multimorbidity: A prospective cohort study.

BACKGROUND: In developing countries, including China, solid-fuel-based heating and cooking is common. For older people, the multimorbidity prevalence is exceptionally high. Nevertheless, studies on the associations of indoor solid fuels use, especially switching fuels types, on multimorbidity in middle-aged and older people is scarce. METHODS: Data from five waves of the China Health and Retirement Longitudinal Study were used in this study. Indoor fuels were classified as solid or clean fuels. Physical-psychological-cognitive multimorbidity (PPC-multimorbidity) was defined as the simultaneous presence of three disease types (physical illness, psychological disorders, cognitive impairment). Using Cox proportional risk models, hazard ratios (HRs) and 95 % confidence intervals (95 % CI) were calculated to investigate the associations of heating- and cooking-related baseline indoor fuels and switching indoor fuels with PPC-multimorbidity incidence. RESULTS: In the heating (n=3121, mean age=56.55 years, male proportion=54.25 %) and cooking (n=3574, mean age=56.67 years, male proportion=52.94 %) analyses, 75.07 % and 45.64 % of the participants used solid fuels at baseline, and 564 (18.07 %) and 613 (17.15 %) PPC-multimorbidity cases were diagnosed during follow-up, respectively. Participants with baseline heating- and cooking-based solid fuels use had greater PPC-multimorbidity incidences [HRs (95 % CIs): 1.23 (0.98, 1.55) and 1.44 (1.21, 1.73)], respectively. Additionally, combined baseline heating- and cooking-based solid fuels use was associated with even greater PPC-multimorbidity incidence [HR (95 % CI): 1.55 (1.18, 2.04)]. Persistent solid fuels use obviously increased the PPC-multimorbidity incidence [HRs (95 % CIs): 2.43 (1.67, 3.55) for heating and 2.63 (2.03, 3.40) for cooking]. Moreover, switching from solid to clean fuels was associated with a significantly decreased PPC-multimorbidity incidence [HRs (95 % CIs): 0.27 (0.20, 0.35) for heating and 0.36 (0.28, 0.46) for cooking]. CONCLUSIONS: Long-term solid-fuels use is associated with an increased PPC-multimorbidity incidence, and switching to cleaner fuels is associated with a decreased PPC-multimorbidity incidence in adults aged ≥45 years.

The role of NLRP6 in the development and progression of neurological diseases.

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.

Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy.

Oncolytic adenovirus-mediated gene therapy shows promise for cancer treatment; however, the systemic delivery of oncolytic adenovirus to tumors remains challenging. Recently, mesenchymal stem cells (MSCs) have emerged as potential vehicles for improving delivery. Yet, because the oncolytic adenovirus replicates in MSCs, balancing MSC viability with viral load is key to achieving optimal therapeutic effect. We thus developed an all-in-one Tet-on system that can regulate replication of oncolytic adenovirus. Then, we loaded the novel oncolytic adenovirus carrying interleukin (IL)-24 and/or Endostatin in human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) for glioma therapy. In vitro assays demonstrated that this novel oncolytic adenovirus could efficiently replicate and kill glioma cells while sparing normal cells. Moreover, doxycycline effectively regulated oncolytic adenovirus replication in the hUCB-MSCs. The doxycycline induction group with dual expression of IL-24 and Endostatin exhibited significantly greater antitumor effects than other groups in a xenograft model of glioma. Thus, this strategy for systemic delivery of oncolytic adenovirus with its oncolytic activity controlled by a Tet-on system is a promising method for achieving antitumor efficacy in glioma, especially for metastatic tumors.