Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

A cross-sectional study: family communication, anxiety, and depression in adolescents: the mediating role of family violence and problematic internet use.

OBJECTIVE: The objective of this study is to explore the relationship between family communication, family violence, problematic internet use, anxiety, and depression and validate their potential mediating role. METHODS: The study population consisted of Chinese adolescents aged 12 to 18 years, and a cross-sectional survey was conducted in 2022. Structural equation models were constructed using AMOS 25.0 software to examine the factors that influence adolescent anxiety and depression and the mediating effects of problematic internet use and family violence. RESULTS: The results indicate that family communication was significantly and negatively related to family violence (ß = -.494, p < 0.001), problematic internet use (ß = -.056, p < .05), depression (ß = -.076, p < .01), and anxiety (ß = -.071, p < .05). And the finds also indicate that family violence mediated the relationships between family communication and depression (ß = -.143, CI: -.198 -.080), and between family communication and anxiety (ß = -.141; CI: -.198 -.074). Chain indirect effects between family communication and depression (ß = -.051; CI: -.081 -.030) or anxiety (ß = -.046; CI: -.080 -.043) via family violence and then through problematic internet use were also found in the present study. CONCLUSIONS: In conclusion, positive family communication is crucial in reducing anxiety and depression in adolescents. Moreover, problematic internet use and family violence mediate the effects of positive family communication on anxiety and depression. Therefore, improving family communication and promoting interventions aimed at reducing family violence and problematic internet use can help reduce anxiety and depression in adolescents, thus promoting their healthy development.

Concurrent Hearing and Genetic Screening of 180,469 Neonates with Follow-up in Beijing, China.

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

Access to 3-Sulfonamidoquinolines by Gold-Catalyzed Cyclization of 1-(2'-Azidoaryl)propargylsulfonamides through 1,2-N Migration.

We describe a gold-catalyzed cyclization of 1-(2'-azidoaryl)propargylsulfonamides for the synthesis of 3-sulfonamidoquinolines, featuring a rare and highly selective 1,2-N migration. The key α-imino gold carbene intermediate is generated through an intramolecular nucleophilic attack of the azide group to the Au-activated triple bonds in a 6-endo-dig manner.

Influence factors analysis of COVID-19 Prevention behavior of chinese Citizens: a path analysis based on the hypothetical model.

BACKGROUND: Under the outbreak of Coronavirus disease 2019 (COVID-19), a structural equation model was established to determine the causality of important factors that affect Chinese citizens' COVID-19 prevention behavior. METHODS: The survey in Qingdao covered several communities in 10 districts and used the method of cluster random sampling. The research instrument used in this study is a self-compiled Chinese version of the questionnaire. Of the 1215 questionnaires, 1188 were included in our analysis. We use the rank sum test, which is a non-parametric test, to test the influence of citizens'basic sociodemographic variables on prevention behavior, and the rank correlation test to analyze the influencing factors of prevention behavior. IBM AMOS 24.0 was used for path analysis, including estimating regression coefficients and evaluating the statistical fits of the structural model, to further explore the causal relationships between variables. RESULTS: The result showed that the score in the prevention behavior of all citizens is a median of 5 and a quartile spacing of 0.31. The final structural equation model showed that the external support for fighting the epidemic, the demand level of health information, the cognition of (COVID-19) and the negative emotions after the outbreak had direct effects on the COVID-19 prevention behavior, and that negative emotions and information needs served as mediating variables. CONCLUSIONS: The study provided a basis for relevant departments to further adopt epidemic prevention and control strategies.

A miRNA-Encoded Small Peptide, vvi-miPEP171d1, Regulates Adventitious Root Formation.

One of the biggest challenges in clonal propagation of grapevine (Vitis vinifera) is difficulty of rooting. Adventitious root initiation and development are the critical steps in the cutting and layering process of grapevine, but the molecular mechanism of these processes remains unclear. Previous reports have found that microRNA (miRNA)-encoded peptides (miPEPs) can regulate plant root development by increasing the transcription of their corresponding primary miRNA. Here, we report the role of a miPEP in increasing adventitious root formation in grapevine. In this study, we performed a global analysis of miPEPs in grapevine and characterized the function of vvi-miPEP171d1, a functional, small peptide encoded by primary-miR171d. There were three small open reading frames in the 500-bp upstream sequence of pre-miR171d. One of them encoded a small peptide, vvi-miPEP171d1, which could increase the transcription of vvi-MIR171d Exogenous application of vvi-miPEP171d1 to grape tissue culture plantlets promoted adventitious root development by activating the expression of vvi-MIR171d Interestingly, neither exogenous application of the vvi-miPEP171d1 peptide nor overexpression of the vvi-miPEP171d1 coding sequence resulted in phenotypic changes in Arabidopsis (Arabidopsis thaliana). Similarly, application of synthetic ath-miPEP171c, the small peptide encoded by the Arabidopsis ortholog of vvi-MIR171d, inhibited the growth of primary roots and induced the early initiation of lateral and adventitious roots in Arabidopsis, while it had no effect on grape root development. Our findings reveal that miPEP171d1 regulates root development by promoting vvi-MIR171d expression in a species-specific manner, further enriching the theoretical research into miPEPs.

Structure-activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure-activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 µM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.

Sodium butyrate causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway.

Aggregation of α-Synuclein is central to the pathogenesis of Parkinson's disease (PD). However, these α-Synuclein inclusions are not only present in brain, but also in gut. Enteroendocrine cells (EECs), which are directly exposed to the gut lumen, can express α-Synuclein and directly connect to α-Synuclein-containing nerves. Dysbiosis of gut microbiota and microbial metabolite short-chain fatty acids (SCFAs) has been implicated as a driver for PD. Butyrate is an SCFA produced by the gut microbiota. Our aim was to demonstrate how α-Synuclein expression in EECs responds to butyrate stimulation. Interestingly, we found that sodium butyrate (NaB) increases α-Synuclein mRNA expression, enhances Atg5-mediated autophagy (increased LC3B-II and decreased SQSTM1 (also known as p62) expression) in murine neuroendocrine STC-1 cells. Further, α-Synuclein mRNA was decreased by the inhibition of autophagy by using inhibitor bafilomycin A1 or by silencing Atg5 with siRNA. Moreover, the PI3K/Akt/mTOR pathway was significantly inhibited and cell apoptosis was activated by NaB. Conditioned media from NaB-stimulated STC-1 cells induced inflammation in SH-SY5Y cells. Collectively, NaB causes α-Synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway.

A systematic review of advances in intestinal microflora of fish.

Intestinal flora is closely related to the health of organisms and the occurrence and development of diseases. The study of intestinal flora will provide a reference for the research and treatment of disease pathogenesis. Upon hatching, fish begin to acquire a microbial community in the intestine. In response to the environment and the host itself, the fish gut eventually develops a unique set of microflora, with some microorganisms being common to different fish. The existence of intestinal microorganisms creates an excellent microecological environment for the host, while the fish symbiotically provides conditions for the growth and reproduction of intestinal microflora. The intestinal flora and the host are interdependent and mutually restrictive. This review mainly describes the formation of fish intestinal flora, the function of normal intestinal flora, factors affecting intestinal flora, and a series of fish models.

[Overview of systematic reviews on Kuntai Capsules in treatment of perimenopausal syndrome].

To evaluate the efficacy and safety of Kuntai Capsules in the treatment of perimenopausal syndrome. Systematic reviews on Kuntai Capsules in the treatment of perimenopausal syndrome were retrieved from Chinese and English databases from database establishment to August 31, 2020. AMSTER-2 scale, GRADE scale and ROBIS tools were used respectively to evaluate the methodological quality, evidence quality level and bias risk of the finally included systematic reviews. A total of 6 systematic reviews with 28 outcome indicators were included. The results of AMSTER-2 methodological quality assessment showed that one of the six systematic reviews was of low quality, and the other five were of extremely low quality. GRADE scale showed that 28 clinical outcome indicators were evaluated, three of which were intermediate-level ones, and the rest were low-level or very low-level ones. Two evidences of the three intermediate evidences were total efficiency, and the other intermediate evidence was Kupperman score. ROBIS bias risk assessment showed all the included studies were of high risk. The results showed that, Kuntai Capsules were effective in the treatment of perimenopausal symptoms, such as hot flashes and sweating. The improvement of E_2 level was not as good as that in the menopause hormone therapy group, but the incidence of adverse reactions was lower than that in the menopause hormone therapy group. However, the quality of evidence needs to be improved due to the low quality of methodology and high risk of bias. It is suggested that systematic review and reasonable design should be carried out in the future, and attention should be paid to the registration of research schemes. In addition, the research reports shall be prepared according to PRISMA statement.

Sodium Butyrate Exacerbates Parkinson's Disease by Aggravating Neuroinflammation and Colonic Inflammation in MPTP-Induced Mice Model.

The abnormal production of short chain fatty acid (SCFAs) caused by gut microbial dysbiosis plays an important role in the pathogenesis and progression of Parkinson's disease (PD). This study sought to evaluate how butyrate, one of SCFAs, affect the pathology in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treated mouse model of PD. Sodium butyrate (NaB; 165 mg/kg/day i.g., 7 days) was administrated from the day after the last MPTP injection. Interestingly, NaB significantly aggravated MPTP-induced motor dysfunction (P < 0.01), decreased dopamine (P < 0.05) and 5-HT (P < 0.05) levels, exacerbated declines of dopaminergic neurons (34%, P < 0.05) and downregulated expression of tyrosine hydroxylase (TH, 47%, P < 0.05), potentiated glia-mediated neuroinflammation by increasing the number of microglia (17%, P < 0.05) and activating astrocytes (28%, P < 0.01). In vitro study also confirmed that NaB could significantly exacerbate pro-inflammatory cytokines expression (IL-1ß, 4.11-fold, P < 0.01; IL-18, 3.42-fold, P < 0.01 and iNOS, 2.52-fold, P < 0.05) and NO production (1.55-fold, P < 0.001) in LPS-stimulated BV2 cells. In addition, NaB upregulated the expression of pro-inflammatory cytokines (IL-6, 3.52-fold, P < 0.05; IL-18, 1.72-fold, P < 0.001) and NLRP3 (3.11-fold, P < 0.001) in the colon of PD mice. However, NaB had no effect on NFκB, MyD88 and TNF-α expression in PD mice. Our results indicate that NaB exacerbates MPTP-induced PD by aggravating neuroinflammation and colonic inflammation independently of the NFκB/MyD88/TNF-α signaling pathway.

A Rare Instance of Primary Oncocytic Schneiderian Papilloma of Middle Ear and Eustachian Tube With a Combined Trans Oto and Nasal Approach Resection.

Oncocytic Schneiderian papillomas are rare tumours which usually arise in the sinonasal region. This paper presents, to the authors' knowledge, the first reported case of oncocytic Schneiderian papilloma arising primarily from the middle ear and eustachian tube. The resection of the tumor was performed with an endoscopic approach of combined trans oto and nasal. Oncocytic Schneiderian papilloma in the middle ear and eustachian tube is extremely rare as a primary lesion and challenging to manage. Very few documents have provided guide of resection using the endoscopic approach when this tumor extends to involve the eustachian tube. Our study illustrates that the endoscopic approach of combined trans oto and nasal is a good choice for tumor resection of middle ear and eustachian tube.

Effect of the autism-associated lncRNA Shank2-AS on architecture and growth of neurons.

The pathogenic mechanism of autism is complex, and current research has shown that long noncoding RNAs (lncRNAs) may play important roles in this process. The antisense lncRNA of SH3 and multiple ankyrin repeat domains 2 (Shank2-AS) is upregulated in patients with autism spectrum disorder (ASD), whereas the expression of its sense strand gene Shank2 is downregulated. In neuronal cells, Shank2-AS and Shank2 can form a double-stranded RNA and inhibit Shank2 expression. Overexpression of Shank2-AS decreases neurite numbers and lengths, thereby inhibiting the proliferation of neuronal cells and promoting their apoptosis. Overexpression of Shank2 inhibits the abovementioned effects of Shank2-AS, and transfection of a vector containing the 10th intron of Shank2 (Shank2-AS is reverse-transcribed from this region) also blocks the function of Shank2-AS. Shank2 small interfering RNA plays a role similar to Shank2-AS. Therefore, Shank2-AS is abnormally expressed in patients with ASD and may affect the structure and growth of neurons by regulating Shank2 expression, thereby facilitating the development of ASD.

[Evaluation with different measuring methods for the alveolar bone change of ridge preservation in molar sites].

OBJECTIVE: To investigate the changes of the vertical height and width of the alveolar bone six months after the alveolar ridge preservation in periodontal compromised molar sites of severe alveolar bone defects with clinical direct measurement, parallel periapical radiographs, and cone-beam computed tomography (CBCT), and to analyze the effect of the three different methods of measurement. METHODS: In this study, 20 subjects requiring tooth extraction on account of periodontal disease with a total of 23 extracted molars were enrolled. Extractions were performed atraumatically and patients were received alveolar ridge preservation procedure with Bio-Oss and Bio-Gide. Clinical direct measurements were taken after tooth extraction and during the implant surgery 6 months later, CBCT scans and parallel periapical radiographs were taken immediately after ridge preservation and 6 months later. The changes of alveolar ridge width and vertical height after six months were measured and analyzed through the above-mentioned three methods and the similarities and differences of the measured effect were compared. RESULTS: There were no significant difference of alveolar vertical height in the center of the extraction sites, the center of distal aspect, and distobuccal aspect between the clinical direct measurements and the CBCT measurements (P>0.05), alveolar vertical height in other points and alveolar width measurements were statically significant (P<0.05). After 6 months, 10 sites of 10 subjects were received a flap and re-entered to perform dental implants surgery. The vertical height in the center of alveolar increased significantly and the changes of alveolar vertical height of clinical direct and CBCT measurement were (6.15 ± 1.73) mm and (6.59 ± 2.53) mm, respectively. The measurements of the width of the alveolar bone were (8.45 ± 1.18) mm and (8.52 ± 1.27) mm, respectively. The measurements of the two methods were not statistically significant (P>0.05). The change of the alveolar height in the center of the extraction socket after six months measured by parallel periapical was (5.84 ± 4.28) mm, which was closed to the clinical direct measurement and the CBCT measurement. CONCLUSION: Clinical direct measurement and CBCT measurement were largely consistent in the evaluation of the alveolar bone height and width after the alveolar ridge preservation using deproteinized boving bone mineral (DBBM, Bio-Oss) and bioabsorbable collagen membrane (Bio-Gide) in periodontal compromised molar sites of severe bone defects.

Metformin versus insulin for gestational diabetes mellitus: a meta-analysis.

The aim of the present meta-analysis was to determine the efficacy and safety of metformin for the treatment of women with gestational diabetes mellitus (GDM). We searched databases, including PubMed, Embase and the Cochrane Central Register of Controlled Trials, for randomized controlled trials (RCTs) comparing metformin and insulin treatments in women with GDM. We carried out statistical analyses using RevMan 2011 and used the Grading of Recommendations, Assessment, Development, and Evaluations profiler to rate the quality of evidence of the primary outcomes. We analysed eight studies involving 1592 subjects. Meta-analysis of the RCTs showed that metformin had statistically significant effects on pregnancy-induced hypertension [PIH; risk ratio (RR) 0.54; 95% confidence interval (CI) 0.31, 0.91]. However, its effects on neonatal hypoglycaemia (RR 0.80; 95% CI 0.62, 1.02), rate of large-for-gestational age infants (RR 0.77; 95% CI 0.55, 1.08), respiratory distress syndrome (RR 1.26; 95% CI 0.67, 2.37), phototherapy (RR 0.94; 95% CI 0.67, 1.31) and perinatal death (RR 1.01; 95% CI 0.11, 9.53) were not significant. Our analyses suggest that there is no clinically relevant difference in efficacy or safety between metformin and insulin; however, metformin may be a good choice for GDM because of the lower risk of PIH. The advantages of metformin in terms of glycaemic control, PIH incidence and gestational age at birth are unclear, and should be verified in further trials.

The Epidemiological Characteristics of Beijing Lineage Mycobacterium tuberculosis from a National Referral Center in China.

Our study was to investigate the epidemiological characteristics of M.tuberculosis from a national tuberculosis referral center in China. All strains isolated from TB patients, were genotyped by the RD105 deletion, 8 and 51 SNP loci and VNTR. The high differentiation SNPs of modern Beijing strains were analyzed for protein function and structure. 413 M. tuberculosis were included. Of 379 Beijing lineage M. tuberculosis, 'modern' and 'ancient' strains respectively represented 85.5% (324/379) and 14.5% (55/379). Rv2494 (V48A) and Rv0245 (S103F) were confirmed as high differentiation SNPs associated with modern strains. In a word, Modern Beijing lineage M.tuberculosis was dominant and the structural models suggested that modern sub-lineage may more easily survive in 'extreme' host condition.

Phase I dose-escalation study of aflibercept plus docetaxel in nasopharyngeal carcinoma and other solid tumors.

AIM: To confirm whether the aflibercept dose, plus docetaxel, in western study TCD6120 is appropriate for Chinese patients with nasopharyngeal carcinoma (NPC) and other solid tumors. MATERIALS & METHODS: To assess dose-limiting toxicity of every 3-week 4 mg/kg or 6 mg/kg aflibercept plus 75 mg/m(2) docetaxel. RESULTS: Previously treated patients (16 with NPC and 4 with lung cancer) were enrolled. At 6 mg/kg aflibercept: one dose-limiting toxicity was seen (neutropenic infection); the most frequently reported all-grade adverse events were oropharyngeal pain, stomatitis and alopecia; the most frequently reported grade 3/4 adverse events were oropharyngeal pain, stomatitis and neutropenic infection. Eleven patients had partial response and 3 had stable disease. CONCLUSION: Preliminary efficacy data for docetaxel/aflibercept are encouraging in Chinese patients with NPC. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry ( ClinicalTrials.gov , NCT01148615).

A Pilot Study on a Possible Mechanism behind Olfactory Dysfunction in Parkinson's Disease: The Association of TAAR1 Downregulation with Neuronal Loss and Inflammation along Olfactory Pathway.

Parkinson's disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson's Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs.

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson's disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.