Autophagy Blockage Enhancing Photothermal and Chemodynamic Synergistic Therapy Based on HCQ/CuS Nanoplatform.

As an intracellular protective mechanism, autophagy has the potential to significantly impair the therapeutic effects of photothermal therapy (PTT) and chemodynamic therapy (CDT), which helps cancer cells survive under harsh conditions, such as high temperature and reactive oxygen species (ROS). In this study, an autophagy blockage enhanced PTT and CDT synergistic therapy nanoplatform is constructed by loading hydroxychloroquine (HCQ) with autophagy inhibitory effect into hollow copper sulfide (HCuS). Specifically, HCuS produces toxic ROS through Fenton-like reaction in the tumor microenvironment (TME). At the same time, PTT-mediated temperature elevation of the tumor region accelerates the Fenton-like reaction and ROS production, enhancing the therapeutic effect of CDT. Furthermore, the internal autophagy inhibitor HCQ significantly blocks the fusion of autophagosomes and lysosomes by deacidifying lysosomes, cutting off the self-protection mechanism of cancer cells, and amplifying the combined treatment of PTT and CDT. Both in vitro and in vivo results demonstrate that the combination of photothermal-enhanced chemodynamic therapy with inhibition of autophagy provides new insights into designing multifunctional therapeutic nanoagents.

Triiodothyronine (T3) promotes browning of white adipose through inhibition of the PI3K/AKT signalling pathway.

Obesity arises from an imbalance between energy consumption and energy expenditure, and thyroid hormone levels serve as a determinant of energy expenditure. We conducted experiments at the animal and cellular levels and combined those findings with clinical data to elucidate the role of triiodothyronine (T3) in facilitating the browning of white adipose tissue (WAT) and its underlying mechanism. The results showed (i) the impaired metabolic function of local WAT and the compensatory elevation of systemic thermogenesis in obesity; (ii) T3 treatment of white adipocytes in vitro and local WAT in vivo induced a shift towards a morphologically "brown" phenotype, accompanied by upregulation of mRNA and protein expression of browning-related and mitochondrial function markers, which suggest that T3 intervention promotes the browning of WAT; and (iii) the aforementioned processes could be modulated through inhibition of the PI3K/AKT signalling pathway; however, whether T3 affects the PI3K/AKT signalling pathway by affecting insulin signalling remains to be studied and clarified. The results of our study indicate that T3 treatment promotes browning of WAT through inhibition of the PI3K/AKT signalling pathway; these findings offer novel perspectives regarding the potential of localised therapies for addressing WAT volume in individuals with obesity.

Identification and Expression Analysis of the WOX Transcription Factor Family in Foxtail Millet (Setaria italica L.).

WUSCHEL-related homeobox (WOX) transcription factors are unique to plants and play pivotal roles in plant development and stress responses. In this investigation, we acquired protein sequences of foxtail millet WOX gene family members through homologous sequence alignment and a hidden Markov model (HMM) search. Utilizing conserved domain prediction, we identified 13 foxtail millet WOX genes, which were classified into ancient, intermediate, and modern clades. Multiple sequence alignment results revealed that all WOX proteins possess a homeodomain (HD). The SiWOX genes, clustered together in the phylogenetic tree, exhibited analogous protein spatial structures, gene structures, and conserved motifs. The foxtail millet WOX genes are distributed across 7 chromosomes, featuring 3 pairs of tandem repeats: SiWOX1 and SiWOX13, SiWOX4 and SiWOX5, and SiWOX11 and SiWOX12. Collinearity analysis demonstrated that WOX genes in foxtail millet exhibit the highest collinearity with green foxtail, followed by maize. The SiWOX genes primarily harbor two categories of cis-acting regulatory elements: Stress response and plant hormone response. Notably, prominent hormones triggering responses include methyl jasmonate, abscisic acid, gibberellin, auxin, and salicylic acid. Analysis of SiWOX expression patterns and hormone responses unveiled potential functional diversity among different SiWOX genes in foxtail millet. These findings lay a solid foundation for further elucidating the functions and evolution of SiWOX genes.

Role of apolipoproteins in the pathogenesis of obesity.

Obesity is a state presented by excessive accumulation and abnormal distribution of body fat, with metabolic disorders being one of its distinguishing features. Obesity is associated with dyslipidemia and apolipoproteins are important structural components of plasma lipoproteins. Apolipoproteins influence the progression of obesity by a variety of mechanisms including lipid metabolism, energy expenditure and inflammatory response. In this review, we discuss the role of apolipoproteins in obesity, mechanisms of action as well as their potential as new therapeutic targets.

Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition.

Blood contains a great deal of health-related information and can be used to monitor human health status. Clinically, venous or fingertip blood is usually used for blood tests. However, the clinical application settings of the two sources of blood are unclear. In this study, the proteomes of pairwise venous plasma (VP) and fingertip plasma (FP) were analyzed, and the levels of 3797 proteins were compared between VP and FP. The Spearman's correlation coefficient for the relationship between protein levels of VP and FP ranges from 0.64 to 0.78 (p < 0.0001). The common pathways of VP and FP are related to cell-cell adhesion, protein stabilization, innate immune response, and complement activation, the classical pathway. The VP-overrepresented pathway is related to actin filament organization, while the FP-overrepresented pathway is related to the hydrogen peroxide catabolic process. ADAMTSL4, ADIPOQ, HIBADH, and XPO5 both in VP and FP are potential gender-related proteins. Notably, the VP proteome has a higher interpretation on age than the FP proteome, and CD14 is a potential age-related protein in VP but not in FP. Our study mapped the different proteomes between VP and FP, which can provide value for the standardization of clinical blood tests.

Effects of five years conservation tillage for hedging against drought, stabilizing maize yield, and improving soil environment in the drylands of northern China.

Continuous tillage cultivation positioning trials can provide the basis for maintaining soil health, improving resource utilization efficiency and crop productivity, and achieving sustainable agricultural development. In this study, changes in soil stability and water-holding capacity characteristics were measured under different tillage cultivations from a multi-year microscopic perspective and analyzed to evaluate selected key indicators. Continuous monitoring of rainfall utilization efficiency and yield was carried out for five years. Here, we discuss the role of conservation tillage in buffering and stabilizing rainfall precipitation pattern on the fluctuation and uncertainty of soil water retention and water supply capacity and soil quality. The study was carried out on dryland areas of the Loess Plateau in northern China with eight tillage systems established in 2016: no-tillage (NT); no-tillage and straw (NTS); subsoiling (SU); subsoiling and straw (SUS); rotary tillage (RT); rotary tillage and straw (RTS); conventional tillage (CT); and conventional tillage and straw (CTS). All treatments were applied in conjunction with continuous cropping for five years. The evaluated soil parameters were mean weight diameter (MWD), geometric mean diameter (GMD), >0.25 mm aggregate content (R0.25) of water-stable aggregates (WSAs), soil moisture characteristic curve (SMCC), specific soil water capacity (Cθ), soil organic matter (SOM), rainfall utilization efficiency (RUE), and maize yields for five consecutive years. The MWD, GMD, and R0.25 of SUS were 27.38%, 17.57%, and 7.68% more than CTS (control), respectively. Overall, SOM, average annual RUE, and average annual yields increased by 14.64%, 11.89%, and 9.59%, respectively, compared with 2016. Our results strongly suggest that conservation tillage can considerably improve these characterization indicators. SUS was more effective than CTS in the 0-40 cm soil layer at hedging against drought in the area, stabilizing crop production, and achieving sustainable agricultural development.

Captivity Is Associated With Gut Mycobiome Composition in Tibetan Macaques (Macaca thibetana).

Although recent studies have revealed that gut fungi may play an important functional role in animal biology and health, little is known concerning the effects of anthropogenic pressures on the gut mycobiome. Here, we examined differences of the gut mycobiome in wild and captive populations of Tibetan macaques (Macaca thibetana) targeting the fungal internal transcribed spacer (ITS) and using next generation sequencing. Our findings demonstrate that the diversity, composition, and functional guild of the Tibetan macaque gut mycobiome differ across populations living in different habitats. We found that Tibetan macaques translocated from the wild into a captive setting for a period of 1 year, were characterized by a reduction in fungal diversity and an increase in the abundance of potential gut fungal pathogens compared to wild individuals. Furthermore, we found that the relative abundance of two main fungal guilds of plant pathogens and ectomycorrhizal fungi was significantly lower in captive individuals compared to those living in the wild. Our results highlight that, in addition to bacteria, gut fungi vary significantly among individuals living in captive and wild settings. However, given limited data on the functional role that fungi play in the host's gut, as well as the degree to which a host's mycobiome is seeded from fungi in the soil or ingested during the consumption of plant and animal foods, controlled studies are needed to better understand the role of the local environment in seeding the mycobiome.