Breast cancer therapy has always been a hard but urgent issue. Disruption of mitochondrial Ca homeostasis has been reported as an effective antitumor strategy, while how to contribute to mitochondrial Ca overload effectively is a critical issue. To solve this issue, we designed and engineered a dual enhanced Ca nanogenerator (DECaNG), which can induce elevation of intracellular Ca through the following three ways: Calcium phosphate (CaP)-doped hollow mesoporous copper sulfide was the basic Ca nanogenerator to generate Ca directly and persistently in the lysosomes (low pH). Near-infrared light radiation (NIR, such as 808 nm laser) can accelerate Ca generation from the basic Ca nanogenerator by disturbing the crystal lattice of hollow mesoporous copper sulfide via NIR-induced heat. Curcumin can facilitate Ca release from the endoplasmic reticulum to cytoplasm and inhibit expelling of Ca in cytoplasm through the cytoplasmic membrane. The in vitro study showed that DECaNG could produce a large amount of Ca directly and persistently to flow to mitochondria, leading to upregulation of Caspase-3, cytochrome c, and downregulation of Bcl-2 and ATP followed by cell apoptosis. In addition, DECaNG had an outstanding photothermal effect. Interestingly, it was found that DECaNG exerted a stronger photothermal effect at lower pH due to the super small nanoparticles effect, thus enhancing photothermal therapy. In the in vivo study, the nanoplatform had good tumor targeting and treatment efficacy via a combination of disruption of mitochondrial Ca homeostasis and photothermal therapy. The metabolism of CaNG was sped up through disintegration of CaNG into smaller nanoparticles, reducing the retention time of the nanoplatform in vivo. Therefore, DECaNG can be a promising drug delivery system for breast cancer therapy.

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The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the epidemiological and radiographical characteristics of asymptomatic infections associated with COVID-19. Methods: Data on the epidemiological and radiographical characteristics of asymptomatic infections were extracted from the existing literature. Pooled proportions with 95% confidence intervals were then calculated using a random effects model. Results: A total of 104 studies involving 20,152 cases were included. The proportion of asymptomatic individuals among those with COVID-19 was 13.34% (10.86%-16.29%), among which presymptomatic and covert infections accounted for 7.64% (4.02%-14.04%) and 8.44% (5.12%-13.62%), respectively. The proportions of asymptomatic infections among infected children and healthcare workers were 32.24% (23.08%-42.13%) and 36.96% (18.51%-60.21%), respectively. The proportion of asymptomatic infections was significantly higher after 2020/02/29 than before (33.53% vs 10.19%) and in non-Asian regions than in Asia (28.76% vs 11.54%). The median viral shedding duration of asymptomatic infections was 14.14 days (11.25-17.04). A total of 47.62% (31.13%-72.87%) of asymptomatic infections showed lung abnormalities, especially ground-glass opacity (41.11% 19.7%-85.79%). Conclusions: Asymptomatic infections were more commonly found in infected children and healthcare workers and increased after 2020/02/29 and in non-Asian regions. Chest radiographical imaging could be conducive to the early identification of asymptomatic infections.

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Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells. We posit FTY720 can induce an anergy-polarized phenotype switch on DCs in vitro, especially upon endotoxic activation. A lipopolysaccharide (LPS)-induced mouse bone marrow-derived dendritic cell (BMDC) activation model was employed to test FTY720-induced phenotypic changes on immature and mature DCs. Specifically, methods for morphology, nanostructure, cytokine production, phagocytosis, endocytosis and specific antigen presentation studies were used. FTY720 induced significant alterations of surface markers, as well as decline of shape indices, cell volume, surface roughness in LPS-activated mature BMDCs. These phenotypic, morphological and topographical changes were accompanied by FTY720-mediated down-regulation of proinflammatory cytokines, including IL-6, TNF-α, IL-12 and MCP-1. Together with suppressed nitric oxide (NO) production and CCR7 transcription in FTY720-treated BMDCs with or without LPS activation, an inhibitory mechanism of NO and cytokine reciprocal activation was suggested. This implication was supported by the impaired phagocytotic, endocytotic and specific antigen presentation abilities observed in the FTY720-treated BMDCs. In conclusion, we demonstrated FTY720 can induce anergy-polarization in both immature and LPS-activated mature BMDCs. A possible mechanism is FTY720-mediated reciprocal suppression on the intrinsic activation pathway and cytokine production with endpoint exhibitions on phagocytosis, endocytosis, antigen presentation as well as cellular morphology and topography.

BackgroundPrevious studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, up to now, there still lacks a large sample study to analyze the relationship between OSCC in a Chinese population and oral HPV infection. In the present study, we used a meta-analysis to evaluate the relationship of OSCC with HPV infection in a Chinese population.MethodsThe reports on HPV and OSCC in a Chinese population published between January, 1994, and September, 2011 were retrieved via CNKI/WANFANG/OVID/MEDLINE databases. According to the inclusion criteria, we selected 18 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the fixed effects model.ResultsThe overall positive rates of HPV and HPV16 in OSCC were 58.0% (354/610; 95% confidence interval [CI], 54.1–61.9) and 47.47% (169/356; 95% CI: 42.3–52.7), respectively; which were significantly higher than those in normal controls 10.44% (26/249; 95% CI: 7.2–14.7) and 7.1% (13/182; 95% CI: 4.2–11.8). Quantitative meta-analysis revealed that, compared with normal controls, the combined odds ratios of OSCC with HPV or HPV16 infection were 12.7 (95% CI: 8.0–20.0) and 9.0 (95% CI: 5.1–15.6), respectively. Both Begg's test and funnel plots revealed that no publication bias was found in this present study (P>0.05).ConclusionsHigh incidences of HPV infection (mainly involving HPV16) were found in the samples of Chinese OSCC. For the Chinese population, HPV infection elevates the risk of OSCC tumorigenesis. Prophylactic HPV-vaccination may reduce the burden of HPV-related OSCC in China.

Multidrug resistance (MDR) of a tumor is the main cause of failure of clinical chemotherapy. Herein, we report a simple, yet versatile, tumor-targeting "calcium ion nanogenerator" (TCaNG) to reverse drug resistance by inducing intracellular Ca 2+ bursting. Consequently, the TCaNG could induce Ca 2+ bursting in acidic lysosomes of tumor cells and then reverse drug resistance according to the following mechanisms: (i) Ca 2+ specifically accumulates in mitochondria, suppressing cellular respiration and relieving tumor hypoxia, thus inhibiting P-glycoprotein biosynthesis by downregulating HIF-1α expression. (ii) Ca 2+ -bursting-induced respiratory depression blocks intracellular ATP production, which further leads to the P-gp incompetence. As a result, the TCaNG could decrease the IC 50 of DOX to MCF-7/ADR cells by approximately 30 times and reduce the proliferation of drug-resistant tumors by approximately 13 times without obvious side effects. This simple, safe, and effective "Ca 2+ bursting" strategy holds the potential for clinical application in tumor treatment.

The dwarf architecture is an important and valuable agronomic trait in watermelon breeding and has the potential to increase fruit yield and reduce labor cost in crop cultivation. However, the molecular basis for dwarfism in watermelon remains largely unknown. In this study, a recessive dwarf allele (designated as Cldf (Citrullus lanatus dwarfism)) was fine mapped in a 32.88 kb region on chromosome 09 using F2 segregation populations derived from reciprocal crossing of a normal line M08 and a dwarf line N21. Gene annotation of the corresponding region revealed that the Cla015407 gene encoding a gibberellin 3β-hydroxylase functions as the best possible candidate gene for Cldf. Sequence analysis showed that the fourth polymorphism site (a G to A point mutation) at the 3′ AG splice receptor site of the intron leads to a 13 bp deletion in the coding sequence of Cldf in dwarf line N21 and thus results in a truncated protein lacking the conserved domain for binding 2-oxoglutarate. In addition, the dwarf phenotype of Cldf could be rescued by exogenous GA3 application. Phylogenetic analysis suggested that the small multigene family GA3ox (GA3 oxidase) in cucurbit species may originate from three ancient lineages in Cucurbitaceae. All these data support the conclusion that Cldf is a GA-deficient mutant, which together with the cosegregated marker can be used for breeding new dwarf cultivars.