A tumor microenvironment-activatable nanoplatform with phycocyanin-assisted in-situ nanoagent generation for synergistic treatment of colorectal cancer.

The in-situ generation of therapeutic agents in targeted lesions is promising for revolutionizing oncotherapy but is limited by the low production efficiency. Given the specific tumor microenvironment (TME) of colorectal cancer (CRC), i.e., mild acidity, overexpressed H2O2, glutathione (GSH) and H2S, we develop phycocyanin (PC) encapsulated PZTC/SS/HA nanocapsules (NCs) for TME-responsive, protein-assisted "turn-on'' therapy of CRC. The NCs are prepared by sequentially assembling Cu2+-tannic acid (TA) coordination shell, disulfide bond-bearing cross-linker, and hyaluronic acid (HA) on the sacrificial template ZIF-8, thus achieving pH-, GSH-responsiveness, and tumor targeting capability, respectively. Once reaching the CRC sites, the NCs can quickly disintegrate and release Cu2+ and PC, accompanied by subsequent endogenous H2S-triggered generation of copper sulfide (CuS). Significantly, the intracellular sulfidation process can be accelerated by PC, thereby enabling efficient photothermal therapy (PTT) under NIR-Ⅱ laser. Besides, Cu2+-associated chemodynamic therapy (CDT) can be simultaneously activated and enhanced by PTT-induced local hyperthermia and disulfide bond-induced GSH consumption. This CRC-targeted and TME-activated synergistic PTT/CDT strategy displays high therapeutic efficacy both in vitro and in vivo, which can open up a new avenue for biomolecule-assisted in-situ nanoagent generation and effective TME-responsive synergistic treatment of CRC.

Viral Diversity and Epidemiology in Critically Endangered Yangtze Finless Porpoises (Neophocaena asiaeorientalis asiaeorientalis).

The Yangtze finless porpoise (YFP) (Neophocaena asiaeorientalis asiaeorientalis) is a critically endangered freshwater cetacean, with about 1,249 individuals thought to be left in the wild. However, viral entities and viral diseases of YFPs remain obscure. In this study, anal swabs for virome analysis were collected during the physical examination of YFPs in the Tian-E-Zhou Oxbow (TEO) ex situ reserve. A total of 19 eukaryotic viral species belonging to 9 families, including Papillomaviridae, Herpesviridae, Picornaviridae, Picobirnaviridae, Caliciviridae, Retroviridae, Parvoviridae, Virgaviridae, and Narnaviridae, and other unclassified viruses were identified based on metasequencing. Among these detected viruses, a novel herpesvirus (NaHV), two different kobuviruses (NaKV1-2), and six different papillomaviruses (NaPV1 to -6) were considered potential risks to YFPs and confirmed by PCR or reverse transcription-PCR (RT-PCR). Most YFPs sampled were found to harbor one or more kinds of detected viral genomes (52/58 [89.7%]). Surveillance results demonstrated that kobuvirus and herpesvirus displayed obvious age distribution and PVs showed significant gender difference in YFPs. According to species demarcation criteria in individual genera in Papillomaviridae, two novel species (referred to as Omikronpapillomavirus 2 and 3) and four novel isolates of PV were identified in YFPs. Further evolutionary analysis suggested that NaPVs would occupy the mucosal niche and that virus-host codivergence mixed with duplications and host-switching events drives the evolution of cetacean PVs. Divergence times of PVs in YFP and other cetacean reflect the incipient speciation of YFPs. In summary, our findings revealed the potential viral entities, their prevalence, and their evolutionary history in YFPs, which raises an important issue regarding effects of viral infection on the fitness of YFPs. IMPORTANCE The Yangtze finless porpoise (YFP) is the only cetacean species in freshwater following the functional extinction of the baiji (Lipotes vexillifer). Health management, disease treatment, and other special measures are important for maintaining the existing YFP populations, especially in in situ and ex situ reserves. The discovery of potential viral entities and their prevalence in YFPs raises an important issue regarding the effects of viral infection on the fitness of YFPs and may contribute to the conservation of YFPs. The evolutionary history of papillomaviruses in YFP and other cetaceans reflects the phylogeny of their hosts and supports the status of incipient species, opening a window to investigate the evolutionary adaptation of cetaceans to freshwater as well as their phylogeny to remedy the deficiency of fossil evidence.

Effects of dietary adenosine and adenosine 5'-monophosphate supplementation on carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs.

This study investigated the effects of adenosine (ADO) and adenosine 5'-monophosphate (AMP) supplementation on the growth performance, carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs. The pigs were allocated to three treatment groups: the control diet, 0.2%ADO diet, or 0.2%AMP diet. Compared with CON group (CON), both ADO and AMP groups increased in carcass straight length (P < 0.05) and decreased in drip loss (P < 0.05), while AMP group tended to increase in redness value (P = 0.05) and decreased in free amino acid content in longissimus thoracis (LT) muscle (P < 0.05). Additionally, ADO or AMP supplementation increased the ADO or AMP content in serum, adipose tissue, and LT muscle (P < 0.05), as well as the protein level of adenosine 2A receptor (A2a) in adipose tissue (P < 0.05). Moreover, both ADO and AMP groups showed an increase in the expression of lipolysis genes (ATGL and HSL) in adipose tissue (P < 0.05). Overall, AMP supplementation could improve meat quality, and ADO and AMP supplementation regulate the lipid metabolism of finishing pigs.

Quercitrin Rapidly Alleviated Depression-like Behaviors in Lipopolysaccharide-Treated Mice: The Involvement of PI3K/AKT/NF-κB Signaling Suppression and CREB/BDNF Signaling Restoration in the Hippocampus.

Quercitrin (Qc) is a well-known flavonoid compound that exerts anti-inflammation effects on various diseases. The present study aimed to investigate the antidepressant-like response of Qc and its underlying mechanisms concerning neuroinflammation and neuroplasticity in mice with lipopolysaccharide (LPS)-induced depression-like behaviors. The results showed a single dose of Qc (10 mg/kg) produced an antidepressant-like effect at 2 h postadministration and lasted for at least 3 days. The expressions of neuroplasticity signaling molecules of pCREB/BDNF/PSD95/Synapsin1 were upregulated at 2 h, and ERK signaling was upregulated for 3 days in the hippocampus after a single administration of Oc or ketamine. A 5-day treatment of LPS led to depression-like behaviors, including reduced sucrose preference and increased immobility in the tail suspension test or forced swim test, which were all reversed by a single dose of Qc. In LPS-treated mice, Qc reduced the levels of inflammation-related factors including IL-10, IL-1ß, and TNF-α in serum, as well as the activations of PI3K/AKT/NF-κB and MEK/ERK pathways in the hippocampus. Moreover, Qc restored the expressions of pCREB/BDNF/PSD95/Synapsin1 signaling in the hippocampus that were impaired by LPS. LY294002, a PI3K inhibitor, but not PD98059, a MEK inhibitor, produced effects similar to Qc. LY294002 also restored the expressions of pCREB/BDNF/PSD95/Synapsin1 signaling in the hippocampus impaired by LPS. Additionally, subeffective doses of Qc and LY294002 induced behavioral and molecular synergism. Together, the depression-like behaviors in LPS-treated mice were alleviated by a single dose of Qc likely via inhibition of the activations PI3K/AKT/NF-κB inflammation signaling and subsequent improvement of neuroplasticity.

[Sequencing and analyses of the adenovirus polymerase gene in fecal samples of captively bred Rhesus macaques].

OBJECTIVE: In an attempt to study the moleculr characterization and epidemiology of simian adenoviruses in nonhuman primate (NHP) populations. METHODS: We examined a colony of captively bred rhesus macaques (Macaca mulatta) in China for the presence of adenoviral DNA in stool samples. This was done by using the PCR method that targeted the adenovirus polymerase gene, and the PCR positive fragments were cloned for sequencing and phylogenetic analyses. RESULTS: Among the 57 animals analyzed, fecal samples from 12 animals were positive for the presence of adenoviral DNA. The results suggested that the viral DNA clones were primarily segregated into two large groups: SAdV-6 (2 non-redundant sequences) and SAdV-7 (9 non-redundant sequences). In addition, there were three clones with more similarity to SAdV-1, SAdV-3 and HAdV-52 respectively. CONCLUSION: Our data confirmed the prevalence of adenoviral DNA in the feces of NHPs and revealed the adenoviruses in the gastrointestinal tract of the study animals. heterogeneity and phylogenetics of the adenoviruses in the gastrointestinal tract of the study animals.

[The significance of antimitochondrial IgA and IgG in the diagnosis of primary biliary cirrhosis].

OBJECTIVE: To evaluate the sensitivity and the specificity of Anti-M2-3E ELISA for the detection of IgG- and IgA-specific isotypes of antimitochondrial antibody (AMA), and to investigate the significance of antimitochondrial IgA and IgG in the diagnosis of primary biliary cirrhosis (PBC). METHODS: Sera were collected from 107 PBC patients, 87 disease controls and 26 healthy controls, and the antimitochondrial antibodies (IgG and IgA) were detected using indirect immunofluorescence (IFL), Anti-PDC ELISA and Anti-M2-3E ELISA. RESULTS: The AMA IgG positive rate in PBC patients was 90.6% detected by Anti-M2-3E ELISA, which is significantly higher than that (81.3%) detected by IFL(t = 4.32, P < 0.05) and that (72.9%) detected by Anti- PDC ELISA (t = 6.03, P < 0.05). The AMA IgA was positive in 59 of the 107 PBC patients, and 99 of the 107 patients were positive for AMA IgG or/and IgA. 9 of the 20 IFL-negative patients were positive for AMA IgG as indicated by Anti-M2-3E ELISA, 11 of the 20 IFL-negative patients were positive for AMA IgG or/and IgA as indicated Anti-M2-3E ELISA. Compared to patients negative for IgG AMA, patients positive for IgG AMA had more severe histopathology and higher levels of ALP, IgG, and IgM. CONCLUSION: The IgG and IgA Anti- M2-3E ELISAs are more sensitive for the AMA detection than IFN and the Anti-PDC ELISA. The presence of AMA IgG is the characteristics of severe PBC.