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Abstract Background Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5–10% of all cases of acute respiratory illnesses and 4–15% of pneumonia cases in children younger than five years old. Without treatment, severe ADV pneumonia could result in fatality rates of over 50% in cases of emerging strains or disseminated disease. This study aims to uncover the relationship of clinical indicators with primary ADV infection severity, regarding duration of hospitalization and liver injury. Methods In this retrospective study, we collected and analyzed the medical records of 1151 in-patients who met the inclusion and exclusion criteria. According to duration of hospitalization, all patients were divided into three groups. Then the difference and correlation of clinical indicators with ADV infection were analyzed, and the relationship among liver injury, immune cells and cytokines was evaluated. Results The study revealed that patients with a duration of hospitalization exceeding 14 days had the highest percentage of abnormalities across most indicators. This was in contrast to the patients with a hospitalization duration of either less than or equal to 7 days or between 7 and 14 days. Furthermore, correlation analysis indicated that a longer duration of body temperature of ≥ 39°C, bilateral lung lobes infiltration detected by X ray, abnormal levels of AST, PaO2, and SPO2, and a lower age were all predictive of longer hospital stays. Furthermore, an elevated AST level and reduced liver synthesis capacity were related with a longer hospital stay and higher ADV copy number. Additionally, AST/ALT was correlated positively with IFN-γ level and IFN-γ level was only correlated positively with CD4+ T cells. Conclusions The study provided a set of predicting indicators for longer duration of hospitalization, which responded for primary severe ADV infection, and elucidated the possible reason for prolonged duration of hospitalization attributing to liver injury via higher ADV copy number, IFN-γ and CD4+ T cells, which suggested the importance of IFN-γ level and liver function monitoring for the patients with primary severe ADV infection.

Background and aims: In all age, FoShou as a Chinese medicinal herb has been active in various kinds of Traditional Chinese medicine formula to treating diabetes. Hesperidin (HES), the main monomeric component of FoShou, has been extensively investigated for interventions with pathogenic mechanism of diabetes as well as subsequent treatment of associated complications. Islet β-cells have an essential effect on dynamically regulating blood sugar. Functional abnormalities in these cells and their death are strongly associated with the onset of diabetes. Therefore, induction of islet endocrine cell lineage re-editing for damaged βcell replenishment would be a promising therapeutic tool. Previously, it has been found that HES can protect islet β-cells in vivo, But, the regenerative function of HES in islet β cells and its role in promoting differential non-β cells transdifferentiation into β cells and cell fate rewriting associated mechanisms remain unclear.This work focused on investigating whether HES can induce islet α cells transdifferentiation into β cells for achieving damaged β cell regeneration and the causes and possible mechanisms involved in the process. Materials and methods: In brief, 60 mg/kg/d streptozotocin (STZ) was administered intraperitoneally in each male C57bL/6J mouse raised by the high-sugar and high-fat diet (HFD) to create a diabetic mouse model with severe β-cell damage. After 28 consecutive days of HES treatment (160 mg/kg; 320 mg/kg; once daily, as appropriate). Tracing the dynamics of α as well as β cell transformation, together with β cells growth and apoptosis levels during treatment by cell lineage tracing. The self-enforcing transcriptional network on which the cell lineage is based is used as a clue to explore the underlying mechanisms. Guangdong Pharmaceutical University's Animal Experiment Ethics Committee (GDPulac2019180) approved all animal experiments. Results: Localization by cell lineage we find that transdifferentiated newborn β-cells derived from α cells appeared in the islet endocrine cell mass of DM mice under HES'action. Compared to the model group, expressed by Tunel staining and CXCL10 levels the overall apoptosis rate of β-cells of the pancreas were reduced,the inflammatory infiltration feedback from HE staining were lower.Ki-67 positive cells showed enhanced β-cell proliferation. Decreased HbA1c and blood glucose contents, elevated C-Peptide and insulin contents which respond to ability of nascent beta cells. Also upregulated the mRNA levels of MafA, Ngn3, PDX-1, Pax4 and Arx. Moreover, increased the expression of TGR5/cAMP-CREB/GLP-1 in mouse intestinal tissues and GLP-1/GLP-1R and cAMP-CREB/IRS2/PDX-1 in pancreatic tissues. Conclusions: HES directly affects β-cells, apart from being anti-apoptotic and reducing inflammatory infiltration. HES promotes GLP-1 release by intestinal L cells by activating the TGR5 receptor in DM mouse and regulating its response element CREB signaling. GLP-1 then uses the GLP-1/GLP-1R system to act on IRS2, IRS2 as a port to influence α precursor cells to express PDX-1, with the mobilization of Pax4 strong expression than Arx so that α cell lineage is finally reversed for achieving β cell endogenous proliferation.

Off-axis electron holograms in a nonbiprism transmission electron microscope are obtained by amplitude division electron holography. The image sensitivity and fringe quality are not reduced by the spatial coherence of the illuminating electron beam during the holographic process. Resolution of the reconstructed images is decreased by spatial coherence.

ABSTRACT PMA (propidium monoazide) is one of the few methods that are compatible with metagenomic sequencing to characterize the live/intact microbiota. However, its efficiency in complex communities such as saliva and feces is still controversial. An effective method for depleting host and dead bacterial DNA in human microbiome samples is lacking. Here, we systematically evaluate the efficiency of osmotic lysis and PMAxx treatment (lyPMAxx) in characterizing the viable microbiome with four live/dead Gram+/Gram– microbial strains in simple synthetic and spiked-in complex communities. We show that lyPMAxx-quantitative PCR (qPCR)/sequencing eliminated more than 95% of the host and heat-killed microbial DNA and had a much smaller effect on the live microbes in both simple mock and spiked-in complex communities. The overall microbial load and the alpha diversity of the salivary and fecal microbiome were decreased by lyPMAxx, and the relative abundances of the microbes were changed. The relative abundances of Actinobacteria, Fusobacteria, and Firmicutes in saliva were decreased by lyPMAxx, as was that of Firmicutes in feces. We also found that the frequently used sample storage method, freezing with glycerol, killed or injured 65% and 94% of the living microbial cells in saliva and feces, respectively, with the Proteobacteria phylum affected most in saliva and the Bacteroidetes and Firmicutes phyla affected most in feces. By comparing the absolute abundance variation of the shared species among different sample types and individuals, we found that sample habitat and personal differences affected the response of microbial species to lyPMAxx and freezing. IMPORTANCE The functions and phenotypes of microbial communities are largely defined by viable microbes. Through advanced nucleic acid sequencing technologies and downstream bioinformatic analyses, we gained an insight into the high-resolution microbial community composition of human saliva and feces, yet we know very little about whether such community DNA sequences represent viable microbes. PMA-qPCR was used to characterize the viable microbes in previous studies. However, its efficiency in complex communities such as saliva and feces is still controversial. By spiking-in four live/dead Gram+/Gram– bacterial strains, we demonstrate that lyPMAxx can effectively discriminate between live and dead microbes in the simple synthetic community and complex human microbial communities (saliva and feces). In addition, freezing storage was found to kill or injure the microbes in saliva and feces significantly, as measured with lyPMAxx-qPCR/sequencing. This method has a promising prospect in the viable/intact microbiota detection of complex human microbial communities.

Abstract The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

Abstract Objectives This study aimed to investigate the gene expression of angiogenic marker in surgically treated jawbones and femur on a rat model administrated with zoledronic acid. Results No soft tissue fenestration or bone exposure was found in femur. Delayed soft tissue healing was found in both ZA group (3 in mandible, 4 in maxilla) and control group (1 in mandible, 2 in maxilla), while exposed bone was found only in the ZA group (1 in maxilla, 2 in mandible). RT-PCR analysis demonstrated no significant difference in gene expression of angiogenetic markers between ZA-treated and control groups in femur and mandible. In the maxilla, the expression of VEGFA and VEGFR-2 in medium-term ZA group was significantly down-regulated compared with that in the control. The ZA treatment does not change significantly the expression of the angiogenic factors in femur and mandible, but significantly downregulates the expression in maxilla in this rat model. The angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

Abstract Background Psoriasis (PsO) is a T‐cell‐associated inflammatory autoimmune dermatitis. Leucine leucine‐37 (LL‐37) is upregulated in PsO patients and correlated with the area and severity of PsO. However, the exact relation between LL‐37 and T cell‐associated inflammation is not well understood. It is very important to clarify the relationship between LL‐37 and inflammatory response for clinical diagnosis and treatment of PsO. This study investigated the serum levels of LL‐37 and inflammatory cytokines, as well as correlations between them in PsO patients, which aimed to provide new ideas for the diagnosis and treatment of PsO. Methods PsO patients (n = 50) and healthy volunteers (n = 33) were recruited in this study. Skin specimens were stained with hematoxylin and eosin (H&E). The serum levels of LL‐37, T‐helper type 1 (Th1, IFN‐γ), T‐helper type 17 (Th17, IL‐17), T‐helper type 22 (Th22, IL‐22), and T‐helper type 2 cytokines (Th2, IL‐4) were assessed by enzyme‐linked immunosorbent assay. Some of the patients were re‐recruited after treatment to evaluate LL‐37 and cytokines levels. Results Pathological changes were observed in PsO skin lesions. LL‐37, IFN‐γ, IL‐17, and IL‐22 serum levels were much higher in PsO patients than those in healthy volunteers (p .05) was found. LL‐37 level was positively correlated with IFN‐γ, IL‐17, and IL‐22 levels (p

BS-HH-002 is a newly developed drug with excellent antitumor activity, which resulted from the modification and optimization of the side structure of the homoharringtonine (HHT). It is particularly efficient in treatment for acute myeloid leukemia and myelodysplastic syndromes. Here we tested whether BS-HH-002 also had anti-cancer effects on solid tumors, especially pancreatic cancer. The results showed that BS-HH-002 treatment resulted in the complete degradation of the anti-apoptosis protein MCL-1, thereby inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In contrast, BCL-2 and BCL-XL protein levels were still detected in apoptotic cells. Further, we compared HHT and BS-HH-002 in terms of PK and heart toxicity in animals. Compared to HHT, BS-HH-002 quickly reached high blood concentration after intravenous injection or oral administration, without causing obvious cardiac toxicity. These results indicate that BS-HH-002 is a promising new anti-cancer drug to treat pancreatic and other solid tumors.