The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes. In plants, timely transition to a flowering state is crucial for successful reproduction. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis thaliana. We found that EBS contains bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules that bind H3K27me3 and H3K4me3, respectively. We observed co-enrichment of a subset of EBS-associated genes with H3K4me3, H3K27me3, and Polycomb repressor complex 2 (PRC2). Notably, EBS adopted an autoinhibition mode to mediate its switch in binding preference between H3K27me3 and H3K4me3. This binding balance was critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induced early floral transition. Our results identify a bivalent chromatin reader capable of recognizing two antagonistic histone marks, and we propose a distinct mechanism of interaction between active and repressive chromatin states.

Precocious puberty (PP) mostly stems from endocrine disorders. However, its triggering factors, especially for the early onset of partial PP, and the associated pathogenic mechanisms remain ambiguous. In this study, a systematic analysis in the form of a questionnaire of lifestyles, gut microbiome, and serum metabolome data was carried out to examine the pathogenesis of PP in a cohort comprised of 200 girls, with or without PP. The analysis revealed substantial alterations in gut microbiota, serum metabolites, as well as lifestyle patterns in the PP group, which were characterized by an elevated abundance of β-glucuronidase-producing and butyrate-producing bacteria, and excessive lipid concentration with decreased levels of organic nitrogen compounds in the serum of the participants. These differential microbes and metabolites tend to be reliable non-invasive diagnostic biomarkers aiding the early diagnosis of PP and exhibit a strong discriminative power (AUC = 0.93 and AUC = 0.97, respectively). Furthermore, the microbial biomarkers were confirmed in an independent validation cohort (n = 83, AUC = 0.85). Moreover, structural equation modeling revealed that unhealthy dietary habits were the primary contributors for the alteration of gut microbiota and serum metabolites, triggering the imbalance in the host hormones that leads to premature physical development. Our study determines a causal relationship among the gut microbiota, host metabolites, diet, and clinical characteristics of preadolescent girls who experienced early onset of PP, and formulates non-invasive diagnostic tools demonstrating excellent performance for the early detection of PP.

36The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of 37 microorganisms that facilitates efficient digestion of plant fibers. We used 897 38 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, 39 as well as data from ruminant comparative genomics and functional assays to explore 40 the genetic basis of rumen origin and evolution. Comparative analyses reveal that the 41 rumen and the first-chamber stomachs of camels and cetaceans shared a common 42 tissue origin from the esophagus. The rumen recruited genes from other tissues/organs 43 and up-regulated many esophagus genes to aquire functional innovations involving 44 epithelium absorption, improvement of the ketone body metabolism and regulation of 45 microbial community. These innovations involve such genetic changes as 46 ruminant-specific conserved elements, newly evolved genes and positively selected 47 genes. Our in vitro experiements validate the functions of one enhancer, one 48 positively selected gene and two newly evolved antibacterial genes. Our study 49 provides novel insights into the origin and evolution of a complex organ. 50 3Evolutionary biology has a long history of trying to understand how complex organs 51 evolve 1 . The origin of some notable organs has been central to animal evolution, e.g. 52 the eyes of animals 2,3 , electric organs of fishes 4 , mammalian placenta 5,6 and ruminant 53 headgear 7 . Another remarkable organ innovation found in mammals are the 54 multi-chambered stomachs found in the Cetartiodactyla lineages, including Tylopoda 55 (e.g. camels), Tayassuidae (e.g. peccaries), Hippopotamidae (e.g. hippos), Cetacea 56 (e.g. whales) and Ruminantia (Fig. 1). Among these, ruminants have the most complex 57 digestive system in herbivores, allowing efficient uptake of nutrients from plant 58 material by providing a microbial fermentation ecosystem in the highly specialized 59 rumen 8 . Camels (Tylopoda) have three-chambered stomachs and are also sometimes 60 called "pseudo-ruminants" due to their similar ruminating behavior and microbial 61 fermentation taking place in their first-chamber (FC) stomach 9 . The whales (Cetacea) 62 form the sister group of the Ruminantia 10 , however the FC of their four-chambered 63 stomach is mainly used as a temporary storage chamber for ingested food and for 64 mechanical grinding of food items 11 . With the rumen, ruminants obtained a unique 65 evolutionary advantage through superior utilization of short chain fatty acids (SCFAs) 66 from microbial fermentation, which significantly promoted the expansion and 67 diversification of ruminant taxa 12 . The evolutionary innovation of the rumen is 68 therefore interesting not only in its functional complexity and uniqueness, but also 69 because it has greatly benefited humans by providing high-quality nutrition in the shape 70 of highly productive ruminant livestock species 13,14 . 71The anatomical predecessor from which the rumen evolved has been proposed to 72 4 be the esophagus 15 , yet the...

We demonstrate a novel role of phospholipase D in M1-dependent rodent cortical plasticity and M1 PAMs that do not couple to phospholipase D have functionally distinct effects on cortical plasticity than non-biased M1 PAMs. AbstractHighly selective positive allosteric modulators (PAMs) of the M1 subtype of muscarinic acetylcholine receptor have emerged as an exciting new approach for the potential improvement of cognitive function in patients suffering from Alzheimer's disease and schizophrenia. M1 PAM discovery programs have produced a structurally diverse range of M1 PAMs with distinct pharmacological properties, including different levels of agonist activity and differences in signal bias. This includes the recent discovery of novel biased M1 PAMs that can potentiate coupling of M1 to activation of phospholipase C but not phospholipase D (PLD). However, little is known about the role of PLD in M1 signaling in native systems and it is not clear whether biased M1 PAMs will display differences in modulating M1-mediated responses in native tissue. We now report a series of studies using novel PLD inhibitors and PLD knockout mice to show that PLD is necessary for the induction of M1-dependent long-term depression (LTD) in the prefrontal cortex (PFC).Importantly, biased M1 PAMs that do not couple to PLD not only fail to potentiate orthosteric agonist-induced LTD but also block M1-dependent LTD in the PFC. In contrast, biased and nonbiased M1 PAMs act similarly in potentiating M1-dependent electrophysiological responses that are PLD-independent. These findings demonstrate that PLD plays a critical role in the ability of M1 PAMs to modulate certain CNS functions and that biased M1 PAMs function differently in brain regions implicated in cognition.

Aim: To determine whether obesity has an impact on the short-term efficacy of inter sphincteric resection (ISR) for patients with ultra-low rectal or anal canal cancer.Methods: This retrospective study includes 276 patients with rectal or anal canal cancer who received treatment from the Rectal Surgery Group of the Gastrointestinal Surgery Center of West China Hospital. According to the WHO, the overweight has a BMI greater than 25. We compare the intraoperative related indicators, postoperative recovery indicators and the rate of occurrence of complications between Group A and Group B. Results:The time of operation in Group B is apparently longer than that in Group A (143.41 min VS. 130.91 min P < 0.05), the intraoperative blood loss, the anastomotic patterns and the reconstruction pattern are not statistically different. The rate of perianal infection of Group B is significantly higher than that of Group A (6.5% VS. 1.5% P < 0.05), and the rate of incision infection of Group B is significantly higher than that of Group A (5.6% VS. 0.6% P < 0.05). The rate of occurrence of other complications between two groups is not statistically different. Conclusion:Obesity increases the difficulty of performing ISR for ultra-low rectal or anal canal cancers, extends the time of operation, and increases the incidence rate of perianal infection post-operatively. There is no significant difference between the indications of postoperative recovery, and the incidence rate of complications in obese patients and that in normal weight patients. In terms of the short-term effects, the operations for obese patients are safe and effective.

No abstract

Background：In traditional Volume-Controlled Ventilation (VCV) mode, the creation of pneumoperitoneum during laparoscopic surgery may lead to Ventilator-Associated Lung Injury (VALI). Pressure-Controlled Ventilation with Volume Guarantee (PCV-VG) mode ensures providing adequate oxygen supply to patients while reducing the risk of lung injury. Methods：Eligible randomized clinical trials (RCTs) were searched in Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Sino Med, China National Knowledge Infrastructure (CNKI) and Wan-Fang MED without language restriction up to March 2019. The primary outcome of this meta-analysis was airway peak pressure (Ppeak) at 30, 60 or 90 mins after complete CO2 insufflation. This meta-analysis was followed the recommendations of the PRISMA statement. Results：Finally, 9 articles were included. The Ppeak in the PCV-VG group was lower than that in the VCV group, and the difference was statistically significant at 30mins [Mean Difference (MD)= -3.55, 95% Confidence Interval (CI)= -5.13 to -1.98, I2=83%], 60mins [MD= -5.76, 95%CI= -8.15-3.36, I2=93%], 90 mins [MD= -4.59, 95%CI= -5.43-3.74, I2=30%] after complete CO2 insufflation. Meanwhile, PCV-VG mode could effectively reduce airway mean pressure (Pmean) and improve dynamic compliance (Cdyn) of patients after complete CO2 insufflation in laparoscopic surgery compared to VCV mode. However, no significant difference was found in PetCO2, HR, MAP, PH, PaO2, and PaCO2 between the two-ventilation modes. Conclusions: PCV-VG mode are superior to VCV mode in providing adequate oxygenation at lower airway peak pressure and greater dynamic compliance in patients under laparoscopic surgery.

Methylation-based noninvasive molecular diagnostics are easy and feasible tools for the early detection of colorectal cancer (CRC). However, many of them have the limitation of low sensitivity with some CRCs detection failed in clinical practice. In this study, the clinical and pathological characteristics, as well as molecular features of three methylator-groups, defined by the promoter methylation status of SDC2 and TFPI2, were investigated in order to improve the performance of CRC detection. The Illumina Infinium 450k Human DNA methylation data and clinical information of CRCs were collected from The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO) database. CRC samples were divided into three groups, HH (dual-positive), HL (single positive) and LL (dual-negative) according to the methylation status of SDC2 and TFPI2 promoters. Differences in age, tumor location, microsatellite instable status and differentially expressed genes (DEGs) were evaluated among the three groups and these findings were then confirmed in our inner CRC dataset. The combination of methylated SDC2 and TFPI2 showed a superior performance of distinguishing CRCs from normal controls than each alone. Samples of HL group were more often originated from left-side CRCs whereas very few of them were from right-side (P < 0.05). HH grouped CRCs showed a higher level of microsatellite instability and mutation load than other two groups (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). All mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were found in HH group (HH/HL/LL: 51/0/0, P = 0.018). Also there was a significantly older patient age at the diagnosis in HH group. Gene expression analysis identified 37, 84 and 22 group-specific DEGs for HH, HL and LL, respectively. Functional enrichment analysis suggested that HH specific DEGs were mainly related to the regulation of transcription and other processes, while LL specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. The three defined mathylator groups showed great difference in tumor location, patient age, MSI and ECM biological process, which could facilitate the development of more effective biomarkers for CRC detection.