LncRNA 4930581F22Rik promotes myogenic differentiation by regulating the ERK/MAPK signaling pathway.

The skeletal muscle is the largest organ in mammals and is the primary motor function organ of the body. Our previous research has shown that long non-coding RNAs (lncRNAs) are significant in the epigenetic control of skeletal muscle development. Here, we observed progressive upregulation of lncRNA 4930581F22Rik expression during skeletal muscle differentiation. Knockdown of lncRNA 4930581F22Rik hindered skeletal muscle differentiation and resulted in the inhibition of the myogenic markers MyHC and MEF2C. Furthermore, we found that lncRNA 4930581F22Rik regulates myogenesis via the ERK/MAPK signaling pathway, and this effect could be attenuated by the ERK-specific inhibitor PD0325901. Additionally, in vivo mice injury model results revealed that lncRNA 4930581F22Rik is involved in skeletal muscle regeneration. These results establish a theoretical basis for understanding the contribution of lncRNAs in skeletal muscle development and regeneration.

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.

Dysbiosis of intestinal homeostasis contribute to Whitmania pigra edema disease.

Whitmania pigra is widely used in traditional Chinese medicine. However, W. pigra is being threatened by an edema disease with unknown causes (WPE). In this study, a comprehensive exploration of virome, microbiome, and metabolome aberrations in the intestine of W. pigra was performed to address the aetiology of WPE. Virome analysis indicated that eukaryotic viruses did not contribute to WPE, whereas an expansion of Caudovirales was observed in WPE. Compared to the control, the microbial richness and diversity in diseased W. pigra decreased remarkably. Nine genera, including Aeromonas, Anaerotruncus, Vibrio, Proteocatella, Acinetobacter, and Brachyspira were overrepresented in WPE, whereas eleven genera, including Bifidobacterium, Phascolarctobacterium, Lactobacillus, Bacillus and AF12, were enriched in healthy individuals. Furthermore, certain metabolites, especially amino acids, short-chain fatty acids, and bile acids, were found to be linked to intestinal microbiota alterations in WPE. An integration of the microbiome and metabolome in WPE found that dysbiosis of the gut microbiota or metabolites caused WPE. Notably, W. pigra accepted intestinal microbiota transplantation from WPE donors developed WPE clinical signs eventually, and the dysbiotic intestinal microbiota can be recharacterized in this recipient W. pigra. Strikingly, pathological features of metanephridium and uraemic toxin enrichment in the gut indicated a putative interconnection between the gut and metanephridium in WPE, which represents the prototype of the gut-kidney axis in mammals. These finding exemplify the conservation of "microecological Koch's postulates" from annelids to insects and other vertebrates, which provides a direction of prevention and treatment for WPE and opens a new insight into the pathogenesis of aquatic animal diseases from an ecological perspective.

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.

Role of lncRNA Has2os in Skeletal Muscle Differentiation and Regeneration.

Long non-coding RNAs (lncRNAs) regulate a series of physiological processes and play an important role in development, metabolism and disease. Our previous studies showed that lncRNAs involved in skeletal muscle differentiation. Here, we demonstrated that lncRNA Has2os is highly expressed in skeletal muscle and significantly elevated during skeletal cell differentiation. The knockdown of Has2os inhibited myocyte fusion and impeded the expression of the myogenic factors MyHC and Mef2C. Mechanically, Has2os regulates skeletal muscle differentiation by inhibiting the JNK/MAPK signaling pathway. Furthermore, we also revealed that Has2os is involved in the early stage of regeneration after muscle injury, and the JNK/MAPK signaling pathway is activated at both protein and mRNA levels during early repair. Our results demonstrate the new function of lncRNA Has2os, which plays crucial roles during skeletal muscle differentiation and muscle regeneration, providing a basis for the therapy of lncRNA-related muscle diseases.

The genome of an apodid holothuroid (Chiridota heheva) provides insights into its adaptation to a deep-sea reducing environment.

Cold seeps and hydrothermal vents are deep-sea reducing environments that are characterized by lacking oxygen and photosynthesis-derived nutrients. Most animals acquire nutrition in cold seeps or hydrothermal vents by maintaining epi- or endosymbiotic relationship with chemoautotrophic microorganisms. Although several seep- and vent-dwelling animals hosting symbiotic microbes have been well-studied, the genomic basis of adaptation to deep-sea reducing environment in nonsymbiotic animals is still lacking. Here, we report a high-quality genome of Chiridota heheva Pawson & Vance, 2004, which thrives by extracting organic components from sediment detritus and suspended material, as a reference for nonsymbiotic animal's adaptation to deep-sea reducing environments. The expansion of the aerolysin-like protein family in C. heheva compared with other echinoderms might be involved in the disintegration of microbes during digestion. Moreover, several hypoxia-related genes (Pyruvate Kinase M2, PKM2; Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase, LHPP; Poly(A)-specific Ribonuclease Subunit PAN2, PAN2; and Ribosomal RNA Processing 9, RRP9) were subject to positive selection in the genome of C. heheva, which contributes to their adaptation to hypoxic environments.

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.

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus.

Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.

Yueju-Ganmaidazao Decoction confers rapid antidepressant-like effects and the involvement of suppression of NMDA/NO/cGMP signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Yueju-Ganmaidazao Decoction (YG) is a multiherbal medicine prescribed for treatment of mood disorder, consisting of two classical traditional Chinese herbal medicine Yueju and Ganmaidazao. Yueju and Ganmaidazao both are used for depression treatment. The combined decoction of Yueju and Ganmaidazao is prescribed to achieve optimal clinical outcomes by dealing with different symptoms of depression. Recent studies indicated ethanol extract of Yueju was capable to confer rapid antidepressant-like response. The antidepressant activity of YG decoction with fast-onset feature remains to be investigated. AIM OF THE STUDY: Rapid and safe antidepressant treatment is urgently needed. This study aimed to assess the rapid antidepressant-like activity of YG and the underlying mechanism, focusing on NMDA/NO/cGMP signaling. MATERIALS AND METHODS: The optimal doses for immediate and persistent antidepressant-like response were first screened using tail suspension test (TST) and forced swimming test (FST) post a single administration of YG. The rapid action was further confirmed by using the chronic mild stress (CMS) and learned helplessness (LH) paradigms. The expressions of NMDA receptor subunits were evaluated post stress and YG. The contributions of NMDA, NO, and cGMP signaling to the antidepressant effect of YG were investigated systematically using pharmacological interventions. RESULTS: The optimal dose for immediate and persistent antidepressant potential, evidenced with reduced immobility times in TST or FST from 30 min to 7 days, was determined. The rapid antidepressant-like effect was confirmed in CMS and LH paradigms, including instant normalization of sucrose preference behavior. The expression of NMDA subunit NR1 in the hippocampus was reduced from 30 min to 5 days post YG. In animals subjected to CMS and LH, hippocampal NR1 expression increased, reversed by YG. YG's antidepressant-like effect was blunted by pretreatment with the agonists along the signalings including NMDA (75 mg/kg), L-arginine (750 mg/kg) and sildenafil (5 mg/kg) in TST or FST. Conversely, administration of subeffective dose of individual antagonists, including MK-801 (0.05 mg/kg), 7-nitroindazole (30 mg/kg), methylene blue (10 mg/kg), in combination with a subeffective dose of YG, elicited antidepressant effects. CONCLUSION: YG conferred rapid antidepressant-like effects, and the antidepressant response was essentially dependent on suppression of NMDA/NO/cGMP signaling.

Long-term care services and care workers in Hangzhou City, China: A cross-sectional survey.

AIM: This study aims to investigate the organisation and the workforce profile in long-term care facilities in Hangzhou City, China. BACKGROUND: Population ageing calls for an increase in the number of high-quality, long-term care services. Therefore, there is a pressing need to understand how these services are organized and the qualifications of their workforce. METHODS: A cross-sectional questionnaire survey was conducted among 293 care workers in 21 certified long-term care facilities in Hangzhou City, China. Comparison between government-owned and private facilities was conducted. RESULTS: In total, there were 8,898 beds, 5,468 residents and 887 care workers in the facilities surveyed. As the total bed occupancy rate was 61.5%, there appeared to be adequate facilities in the city. The ratio of care workers to residents was similar in both the government-owned and private facilities, 1 care worker to 6.16 residents. For dependent residents, this ratio was 1-3.50. Organisation of the care services in terms of shift pattern, in-job training and care worker's insurance was significantly different between the two types of facilities. Despite the government-owned facilities being better organized than the private ones, both types of aged care facilities had a 24-hr-long shift. Although their monthly wage was similar, care workers in the government-owned facilities received better job-related insurance, were younger, had longer years of aged care work experience, were better educated and held more aged care certificates and received more frequent in-job training than their counterparts in the private facilities. CONCLUSION: The shift arrangement needs to be improved. The low education level, long working hours and low remuneration of care workers were barriers for the development of the long-term care services. IMPLICATIONS FOR NURSING MANAGEMENT: In order to improve the quality of long-term care services in China, the organisation of work, qualifications and payment of care workers need to be improved.

A new gene ontology-based measure for the functional similarity of gene products.

BACKGROUND: Although biomedical ontologies have standardized the representation of gene products across species and databases, a method for determining the functional similarities of gene products has not yet been developed. METHODS: We proposed a new semantic similarity measure based on Gene Ontology that considers the semantic influences from all of the ancestor terms in a graph. Our measure was compared with Resnik's measure in two applications, which were based on the association of the measure used with the gene co-expression and the protein-protein interactions. RESULTS: The results showed a considerable association between the semantic similarity and the expression correlation and between the semantic similarity and the protein-protein interactions, and our measure performed the best overall. CONCLUSION: These results revealed the potential value of our newly proposed semantic similarity measure in studying the functional relevance of gene products.

[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.