Timing outweighs magnitude of rainfall in shaping population dynamics of a small mammal species in steppe grassland.

Climate change-induced shifts in species phenology differ widely across trophic levels, which may lead to consumer-resource mismatches with cascading population and ecosystem consequences. Here, we examined the effects of different rainfall patterns (i.e., timing and amount) on the phenological asynchrony of population of a generalist herbivore and their food sources in semiarid steppe grassland in Inner Mongolia. We conducted a 10-y (2010 to 2019) rainfall manipulation experiment in 12 0.48-ha field enclosures and found that moderate rainfall increases during the early rather than late growing season advanced the timing of peak reproduction and drove marked increases in population size through increasing the biomass of preferred plant species. By contrast, greatly increased rainfall produced no further increases in vole population growth due to the potential negative effect of the flooding of burrows. The increases in vole population size were more coupled with increased reproduction of overwintered voles and increased body mass of young-of-year than with better survival. Our results provide experimental evidence for the fitness consequences of phenological mismatches at the population level and highlight the importance of rainfall timing on the population dynamics of small herbivores in the steppe grassland environment.

Health prevention intervention for chronic tissue fibrosis: Based on the specific expression of CCL19/21 + mast cell.

Chronic tissue fibrosis is a common pathological feature of connective tissue diseases and malignant tumors, and its prevention has been a major focus of relevant research.However, the details of the mechanism of action of tissue-colonizing immune cells in fibroblast migration are unclear. In this study, connective tissue disease tissue specimens and solid tumor specimens were selected to observe the relationship between mast cells and interstitial fibrosis and the expression characteristics of mast cells. Our findings suggest that the number of mast cells in the tissue correlates with the degree of pathological fibrosis and that mast cells specifically express the chemokines CCL19 and CCL21, especially CCL19. CCR7+ fibroblasts are highly expressed in mast cell clusters. The mast cell line HMC-1 regulates CD14+ monocyte-derived fibroblasts via CCL19. In disease tissue fibrosis, mast cell activation may increase the expression of chemokines, especially CCL19, in the tissue, thereby inducing a large number of CCR7-positive fibroblasts to migrate to specific tissues. This study lays a foundation for the mechanism of tissue fibrosis and provides evidence for the mechanism by which mast cells induce fibroblast migration.Through the experimental results of this paper, we can combine the induction factors of chronic tissue fibrosis and put forward targeted health prevention strategies.

Aza-Quasi-Favorskii Reaction: Construction of Highly Substituted Aziridines through a Concerted Multibond Rearrangement Process.

A new molecular rearrangement, the aza-Quasi-Favorskii rearrangement, has been developed for the construction of highly substituted aziridines. Electron-deficient O-sulfonyl oximes react readily with α,α-disubstituted acetophenone-derived enolates to furnish highly substituted aziridines via this unprecedented domino process. In-depth computational studies reveal an asynchronous yet concerted nitrenoid-type rearrangement pathway.

Population variation alters aggression-associated oxytocin and vasopressin expressions in brains of Brandt's voles in field conditions.

Density-dependent change in aggressive behavior contributes to the population regulation of many small rodents, but the underlying neurological mechanisms have not been examined in field conditions. We hypothesized that crowding stress and aggression-associated oxytocin (OT) and arginine vasopressin (AVP) in specific regions of the brain may be closely related to aggressive behaviors and population changes of small rodents. We analyzed the association of OT and AVP expression, aggressive behavior, and population density of Brandt's voles in 24 large semi-natural enclosures (0.48 ha each) in Inner Mongolia grassland. We tested the effects of population density on the OT/AVP system and aggressive behavior by experimentally manipulating populations of Brandt's voles in the grassland enclosures. High density was positively and significantly associated with more aggressive behavior, and increased expression of mRNA and protein of AVP and its receptor, but decreased expression of mRNA and protein of OT and its receptor in specific brain regions of the voles. Our study suggests that changes in OT/AVP expression are likely a result of the increased psychosocial stress that these voles experience during overcrowding, and thus the OT/AVP system can be used as indicators of density-dependent stressors in Brandt's voles.

High housing density increases stress hormone- or disease-associated fecal microbiota in male Brandt's voles (Lasiopodomys brandtii).

Density-dependence is an important mechanism in the population regulation of small mammals. Stressors induced by high-density (e.g., crowding and aggression) can cause physiological and neurological disorders, and are hypothesized to be associated with alterations in gut microbiota, which may in turn reduce the fitness of animals by increasing stress- or disease-associated microbes. In this study, we examined the effects of housing density on the hormone levels, immunity, and composition of gut microbiota in male Brandt's voles (Lasiopodomys brandtii) by conducting two specific housing density experiments with or without physical contact between voles. Voles in high density groups exhibited higher serum corticosterone (CORT), serotonin (5-HT), and immunoglobulin G (IgG) levels, as well as higher testosterone (T) levels only in the experiment with physical contact. Meanwhile, high-density treatments induced significant changes in the composition of gut microbiota by increasing disease-associated microbes. The levels of hormones and immunity (i.e., CORT, 5-HT, and IgG) elevated by the high density treatment were significantly correlated with some specific microbes. These results imply that high-density-induced stress may shape the fitness of animals under natural conditions by altering their gut microbiota. Our study provides novel insights into the potential roles of gut microbiota in the density-dependent population regulation of small rodents as well as the potential mechanisms underlying psychological disorders in humans and animals under crowded conditions.

Dominant and Subordinate Relationship Formed by Repeated Social Encounters Alters Gut Microbiota in Greater Long-Tailed Hamsters.

Social stress can dramatically influence the health of animals via communication between gut microbiota and the HPA system. However, this effect has been rarely investigated among different social ranked animals after chronic repeated social encounters. In this study, we evaluated changes and differences in microbiota among control, dominant, and subordinate male greater long-tailed hamsters (Tscherskia triton) over 28 successive days of repeated social encounter. Our results indicated that as compared with the control group, short-term repeated social encounters significantly altered fecal microbiota of subordinate hamsters, while chronic repeated social encounters altered colonic mucosa-associated microbiota of both dominant and subordinate hamsters. Fecal microbiota showed a transition in composition and diversity on day 2 for the subordinate group but on day 4 for the control and dominant groups under repeated encounters. Compared with their baseline, genus Lactobacillus increased in both dominant and subordinate groups, while genus Bifidobacterium increased in the subordinate group and genus Adlercreutzia increased in the dominant group. Our results suggest that chronic repeated social encounter can alter diversity and composition of gut microbiota of hamsters in both feces and colonic mucosa, but the latter performed better in reflecting the effects of chronic stress on microbiota in this species. Future studies should focus on elucidating how these microbiota alterations may affect animal behavior and fitness.

Correlation of T follicular helper cells and plasmablasts with the development of organ involvement in patients with IgG4-related disease.

Objective: To assess the role of an abnormal immune network in the pathology of IgG4-related disease (IgG4-RD). Methods: Sixteen patients diagnosed with IgG4-RD at our institution were selected. Peripheral immunocompetent cells were immunophenotyped by multicolour flow cytometry to assess the association between clinical manifestation and pathological findings. Results: Compared with healthy controls, IgG4-RD patients showed comparable proportions of Th1 and Th17 cells, but higher proportions of Treg and follicular helper T (Tfh) cells. Further, the proportions of class-switched memory B cells and plasmablasts were higher in patients. Among all phenotypes, in particular, the plasmablast proportion increased from 4.2% (controls) to 16.5% (patients). The serum IgG levels were found to be correlated with the proportions of plasmablasts and Tfh cells, but not with those of other T cell subsets. In patients with extraglandular symptoms, only plasmablasts, Tfh cells and memory Treg cells were increased. Histopathological examination revealed a marked Tfh (CD4+ Bcl6+) cell infiltration; the increase of Tfh cells in the peripheral blood thus reflected the degree of Tfh cell infiltration into the tissue. Although steroid therapy reduced plasmablast and Tfh cell proportions, the memory Treg cell proportion remained unchanged. Conclusion: The association found between Tfh cells and plasmablasts, linked with biological plausibility, suggests that Tfh cells contribute to the pathogenesis of IgG4-RD. Our results also suggested that controlling the Tfh cell-plasmablast axis could be a novel therapeutic strategy for treating IgG4-RD.

Selective [5 + 1] and [5 + 2] Cycloaddition of Ynamides or Propargyl Esters with Benzo[ d]isoxazoles via Gold Catalysis.

Benzo[ d]isoxazoles are found to act as novel nucleophiles to undergo gold-catalyzed [5 + 1] or [5 + 2] cycloaddition reactions with ynamides. The reaction provides a concise and chemoselective access to polysubstituted 2 H-benzo[ e][1,3]oxazines or benzo[ f][1,4]oxazepines. In addition, benzo[ d]isoxazoles can also react with gold-carbene intermediates derived from propargyl esters to afford [5 + 1] annulation products.

Ligand-Effect in Gold(I)-Catalyzed Rautenstrauch Rearrangement: Regio- and Stereoselective Synthesis of Bicyclo[3.2.1]octa-3,6-dienes through Cyclodimerization of 1-Ethynyl-2-propenyl Esters.

Gold(I) complexes bearing sterically demanding phosphine ligands such as tBuXphos catalyze the cascade Rautenstrauch rearrangement/[4 + 3] cycloaddition of 1-ethynyl-2-propenyl esters. The reaction provides an efficient and straightforward route to bicyclo[3.2.1]octa-3,6-dienes with high regio- and stereoselectivity. The formation of the [4 + 3] cycloadducts likely proceeds through the cycloaddition of a gold(I) carbenoid/gold-stabilized allyl cation intermediate with cyclopentadiene arising from Rautenstrauch rearrangement.

Synthesis of functionalized indolizines via gold(i)-catalyzed intramolecular hydroarylation/aromatization of pyrrole-ynes.

A gold-catalyzed intramolecular hydroarylation/aromatization of pyrrole-ynes has been developed. This method provides a concise and straightforward route to functionalized indolizines through the construction of the pyridine ring of indolizines and also allows elaboration of its pyrrole moiety with or without functional groups. In addition, a wide variety of functional groups, such as aryl, alkenyl, alkynyl, pyridyl or thienyl groups, can be easily incorporated into the pyridine unit of the indolizine products under mild conditions. The utility of the indolizine products was demonstrated by their efficient transformations into various C3-functionalized indolizine derivatives.

Association of plasmacytoid dendritic cells with B cell infiltration in minor salivary glands in patients with Sjögren's syndrome.

OBJECTIVES: Sjogren's syndrome (SS) is an autoimmune disease with features of both over-production of specific autoantibodies and organ-specific disorders, mainly sialadenitis and dacryoadenitis. However, little is known about the factors that contribute to lymphocytic infiltration of SS. METHODS: Minor salivary gland (MSG) tissue was obtained from 83 patients with primary SS (pSS) and 95 patients with secondary SS and examined pathologically, and correlation between infiltrated immune cells and histological features was evaluated. RESULTS: Plasmacytoid dendritic cells (pDCs) were increased in MSG of SS compared to Sicca syndrome. The density of pDCs was characteristically correlated with the accumulation of CXCL13(+)CD68(+) macrophages and CXCR5(+)CD19(+) B in the MSG of pSS. In vitro analysis indicated that Type I interferon (IFN) enhanced CXCL13 production by macrophages. Type I IFN was mainly expressed in pDCs and its expression was correlated with the accumulation of CXCL13(+) macrophages in the MSG of pSS. CONCLUSIONS: Our histological findings suggest the possible mechanism of type I IFN-CXCL13 axis during the pathological processes of acute/chronic salivary inflammation in SS; local production of type I IFN by pDCs, induction of CXCL13 production in macrophages by type I IFN, induction of accumulation of CXCR5(+)CD19(+) B cells by CXCL13 in the MSG.

Gold-Catalyzed Ring Expansion of Alkynyl Heterocycles through 1,2-Migration of an Endocyclic Carbon-Heteroatom Bond.

A mild and efficient gold-catalyzed oxidative ring-expansion of a series of alkynyl heterocycles using pyridine-N-oxide as the oxidant has been developed, which affords highly valuable six- or seven-membered heterocycles with wide functional group toleration. The reaction consists of a regioselective oxidation and a chemoselective migration of an endocyclic carbon-heteroatom bond (favored over C-H migration) with the order of migratory aptitude for carbon-heteroatom bonds being C-S>C-N>C-O. In the absence of an oxidant, polycyclic products are readily constructed through a ring-expansion/Nazarov cyclization reaction sequence.

Gold-catalyzed oxidative ring expansion of 2-alkynyl-1,2-dihydropyridines or -quinolines: highly efficient synthesis of functionalized azepine or benzazepine scaffolds.

A gold-catalyzed highly regio- and chemoselective oxidative ring expansion of 2-alkynyl-1,2-dihydropyridines and its analogues using pyridine-N-oxide as the oxidant has been developed. Ring expansion proceeds through exclusive 1,2-migration of a vinyl or phenyl group, whereas no 1,2-H and 1,2-N migration take place. The reaction provides an efficient and attractive route to various types of medium-sized azepine derivatives in generally high to excellent yields with a broad functional group tolerance. DFT studies indicate that the reaction proceeds through the formation of a cyclopropyl gold intermediate, and no gold carbene species is involved.

The JAK inhibitor, tofacitinib, reduces the T cell stimulatory capacity of human monocyte-derived dendritic cells.

OBJECTIVE: Tofacitinib, which is a Janus kinase (JAK) inhibitor, has shown clinical effects in the treatment of rheumatoid arthritis. JAKs are important kinases in lymphocyte differentiation; however, their function in dendritic cells (DCs) is unknown. In this study, the function of JAKs in DCs was investigated with tofacitinib. METHODS: The effects of tofacitinib on the maturation of human monocyte-derived DCs induced by lipopolysaccharide (LPS) stimulation were investigated. In addition, its effects on T cell stimulatory capability was investigated by coculturing with naïve CD45RA-positive T cells. RESULTS: Tofacitinib decreased expression of CD80/CD86 in a concentration-dependent manner in LPS-stimulated DCs; however, it did not affect HLA-DR expression. Tofacitinib suppressed tumour necrosis factor, interleukin (IL)-6 and IL-1ß production without affecting transforming growth factor (TGF)-ß and IL-10 production. Meanwhile, CD80/CD86 expression in DCs was enhanced by type I interferon (IFN) stimulation, and the LPS-induced CD80/CD86 expression was inhibited by an antibody to type I IFN receptor. Furthermore, tofacitinib suppressed production of type I IFN and activation of interferon regulatory factor (IRF)-7, which is a transcription factor involved in CD80/CD86 and type I IFN expression. Tofacitinib also decreased the T cell stimulatory capability of DCs and increased expression of indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2. CONCLUSIONS: Tofacitinib, a JAK1/JAK3 inhibitor, affected the activities of human DCs. It decreased CD80/CD86 expression and T cell stimulatory capability through suppression of type I IFN signalling. These results suggest a novel mode of action for tofacitinib and a pivotal role for JAKs in the differentiation of DCs.

High diversity, close genetic relatedness, and favorable living conditions benefit species co-occurrence of gut microbiota in Brandt's vole.

Introduction: Revealing factors and mechanisms in determining species co-existence are crucial to community ecology, but studies using gut microbiota data are still lacking. Methods: Using gut microbiota data of 556 Brandt's voles from 37 treatments in eight experiments, we examined the relationship of species co-occurrence of gut microbiota in Brandt's voles (Lasiopodomys brandtii) with genetic distance (or genetic relatedness), community diversity, and several environmental variables. Results: We found that the species co-occurrence index (a larger index indicates a higher co-occurrence probability) of gut microbiota in Brandt's voles was negatively associated with the genetic distance between paired ASVs and the number of cohabitating voles in the experimental space (a larger number represents more crowding social stress), but positively with Shannon diversity index, grass diets (representing natural foods), and non-physical contact within an experimental space (representing less stress). Discussion: Our study demonstrated that high diversity, close genetic relatedness, and favorable living conditions would benefit species co-occurrence of gut microbiota in hosts. Our results provide novel insights into factors and mechanisms that shape the community structure and function of gut microbiota and highlight the significance of preserving the biodiversity of gut microbiota.

Convergent evolution toward a slow pace of life predisposes insular endotherms to anthropogenic extinctions.

Island vertebrates have evolved a number of morphological, physiological, and life history characteristics that set them apart from their mainland relatives. However, to date, the evolution of metabolism and its impact on the vulnerability to extinction of insular vertebrates remains poorly understood. This study used metabolic data from 2813 species of tetrapod vertebrates, including 695 ectothermic and 2118 endothermic species, to reveal that island mammals and birds evolved convergent metabolic strategies toward a slow pace of life. Insularity was associated with shifts toward slower metabolic rates and greater generation lengths in endotherms, while insularity just drove the evolution of longer generation lengths in ectotherms. Notably, a slow pace of life has exacerbated the extinction of insular endemic species in the face of anthropogenic threats. These findings have important implications for understanding physiological adaptations associated with the island syndrome and formulating conservation strategies across taxonomic groups with different metabolic modes.

Distal-continual colon interposition for esophageal reconstruction after esophagectomy: Two case reports.

Background: Colon interposition is a complex and time-consuming procedure requiring at least three or four digestive anastomoses. However, the long-term functional outcomes are promising, with an acceptable operative risk. Case presentation: Herein, two cases of esophageal carcinoma that received esophagus reconstruction using the distal continual colon interposition technique have been described. The transverse colon was lifted to the thoracic cavity for the end-to-side anastomosis with the esophagus, and a closure device was used to close the colon instead of severing and isolating the distal end. The duration of the operation was 140 and 150 min, respectively. The blood supply of the colon was maintained during the intervention. The tension-free anastomosis was performed without severe complications, and oral food intake was resumed on postoperative day 6. Neither anastomotic stenosis, antiacid or heartburn, dysphagia, or emptying obstacles nor complaints of diarrhea, bloating, or malodor were reported during the follow-up period. Conclusions: The modified distal-continual colon interposition technique may have the advantages of a short operation time and potential prevention of serious complications caused by the torsion of mesocolon vessels.

Livestock grazing is associated with the gut microbiota and antibiotic resistance genes in sympatric plateau pika (Ochotona curzoniae).

With the overuse of antibiotics in health care and animal husbandry, antibiotic resistance becomes a serious threat to public health. Antibiotic residues from veterinary medicine have increased the dissemination of antibiotic resistance genes (ARGs) by horizontal gene transfer globally, leading to the enrichment of ARGs in wildlife. Plateau pika (Ochotona curzoniae) is a small herbivore endemic to the Qinghai-Tibetan Plateau. Previous studies reveal that pika evolves a coprophagy behavior toward cohabitated yak, which makes the pika population a potential reservoir of ARGs. Yet, little is known about the resistome of pika under different grazing intensities. Here, we sampled the cecum content of pika from three different grazing intensity areas in the Qinghai-Tibetan Plateau to evaluate the effect of grazing on its gut microbiota and resistome. By using the 16S full-length amplicon and metagenomic sequencing, our study revealed that livestock grazing significantly altered the gut microbial community of plateau pika as compared to prohibited grazing areas. We found bacterial lineage Prevotellaceae, Lachnospirales, and RF39 increased in grazing areas. Analysis of the resistome revealed that pika from continuous grazing areas enriched a higher abundance of colistin (MCR) and streptogramin (vat) resistance genes. Moreover, we observed significant correlations between the gut microbial community, ARGs, and mobile genetic element profiles, hinting that pika gut microbiota was an important shaping force of the resistome. In future studies, the continuous monitoring of wildlife gut resistome and environmental antibiotic residues is imperative for a better understanding and for tackling the horizontal gene transfer of ARGs across the wildlife-livestock interface.

Effects of Group Size on Behavior, Reproduction, and mRNA Expression in Brains of Brandt's Voles.

For social animals, a moderate group size is greatly important to maintain their reproductive success. However, the underlying neurobiological mechanism of group size on behavior and reproduction has rarely been investigated. In this study, we examined the effects of group size (1, 2, 4 pairs of adult male and female voles raised per cage) on behavior and reproduction. Meanwhile, the mRNA expression of stress and reproduction response-related genes in male brains was detected. We found that Brandt's voles (Lasiopodomys brandtii) in the large-sized group fight more severely than those in the small-sized group. Meanwhile, male voles were more anxious than females. The average number of embryos and litters per female in the medium-sized group was significantly higher than that of large-sized group. In male voles, stress- or reproduction-response mRNA expressions were more related to final group size or final density due to death caused by fighting. Our results indicated that a moderate group size was beneficial to the reproductive output of Brandt's voles. Our study highlights the combined effects of stress- or reproduction-related gene expression or behavior in regulating the fitness of voles with different group sizes.

Discovery, Structure-Activity Relationship and In Vitro Anticancer Activity of Small-Molecule Inhibitors of the Protein-Protein Interactions between AF9/ENL and AF4 or DOT1L.

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5-10% acute leukemias with poor clinical outcomes. Protein-protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC50 values as low as 1.6 µM. Structure-activity relationship studies of 77 benzothiophene and related indole and benzofuran compounds show that a 4-piperidin-1-ylphenyl or 4-pyrrolidin-1-ylphenyl substituent is essential for the activity. The inhibitors suppressed expression of MLL target genes HoxA9, Meis1 and Myc, and selectively inhibited proliferation of MLL-r and other acute myeloid leukemia cells with EC50 values as low as 4.7 µM. These inhibitors are useful chemical probes for biological studies of AF9/ENL, as well as pharmacological leads for further drug development against MLL-r and other leukemias.