Niche convergence and biogeographic history shape elevational tree community assembly in a subtropical mountain forest.

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.

Stubborn hypoxemia after mild to moderate sedation and analgesia: A case report.

INTRODUCTION: Atelectasis typically denotes the partial or complete collapse of lung segments, lobes, or lobules in individuals, leading to a compromised respiratory function. The prevalence of perioperative atelectasis may be significantly underestimated, particularly among patients subjected to general anesthesia. PATIENT CONCERNS: This article conducts a retrospective analysis of a case involving refractory hypoxemia in a patient with a liver tumor who was admitted to Yanbian University Affiliated Hospital (Yanbian Hospital) after undergoing mild-to-moderate sedation and analgesia outside the operating room. DIAGNOSIS: Based on the results of CT examination and present history, the patient was diagnosed with intraoperative atelectasis. INTERVENTION: After the surgery, the patient was transferred to the recovery ward, where nasal oxygen therapy and nebulized inhalation treatment were administered. Vital signs were closely monitored at the bedside, gradually returning to the preoperative baseline. OUTCOME: Postoperatively, the patient developed atelectasis, with the percentage of lung opacity shown in the image decreasing from 9.2% of the total thoracic cage area to 8.4%. CONCLUSION: During non-intubated intravenous anesthesia, patients with compromised pulmonary conditions are more susceptible to refractory hypoxemia. Therefore, a personalized approach should be adopted regarding oxygen concentration and the dosage and type of medication. Additionally, preparations for appropriate airway management measures are essential to safeguard patient safety in the event of respiratory issues.

Association Between Serum Thyroid Measurements and Hyperhomocysteinemia in Euthyroid Subjects: A Retrospective Cross-Sectional Study.

Objective: The objective of this study was to investigate the association between serum thyroid measurements and homocysteine (HCy) in euthyroid participants. Methods: This retrospective study was based on Hospital Information Systems. After excluding participants with thyroid dysfunction and those who had recently taken medications that affected serum HCy, 775 participants were enrolled. We compared the serum thyroid function measurements of patients with or without hyperhomocysteinemia (HHCy) and analyzed the effect of thyroid indicators on HHCy prevalence and HCy levels. Multivariate regression analysis was utilized to analyze the association of thyroid-stimulating hormone (TSH) and thyroid peroxidase (TPOAb) with HCy. Results: The serum TSH level (2.10 ± 1.06 mIU/L) of HHCy patients (n = 98) was significantly higher than controls (n = 677) (1.65 ± 0.90 mIU/L) (p < 0.05), as was the positive rate of TPOAb (19.4% vs 10.0%, p < 0.05). The serum HCy levels in subjects with TSH within the highest quartile were significantly higher than those in the lowest quartile (13.49 ± 7.78 vs 9.81 ± 3.59 µmol/L, p < 0.05). HCy was also significantly higher in TPOAb-positive patients than in negative subjects (14.06 ± 8.89 vs 11.48 ± 5.47 µmol/L, p < 0.05). Among the TSH quartiles, the prevalence of HHCy showed a similar significant upward trend to that described above. The prevalence of HHCy was also significantly higher in TPOAb-positive patients. The results of multivariate regression analysis suggested that both TSH elevation and TPOAb positivity were independent risk factors for HCy elevation and HHCy prevalence. However, we found no definitive association between linear increases in TPOAb titers and HCy concentrations or HHCy prevalence. Conclusion: Patients with HHCy had significantly higher TSH levels and positive rates of TPOAb. Elevated TSH and positive TPOAb levels were independent risk factors for elevated HCy concentrations and HHCy risk.

Wood decomposition is increased by insect diversity, selection effects, and interactions between insects and microbes.

Biodiversity drives ecosystem processes, but its influence on deadwood decomposition is poorly understood. To test the effects of insect diversity on wood decomposition, we conducted a mesocosm experiment manipulating the species richness and functional diversity of beetles. We applied a novel approach using computed tomography scanning to quantify decomposition by insects and recorded fungal and bacterial communities. Decomposition rates increased with both species richness and functional diversity of beetles, but the effects of functional diversity were linked to beetle biomass, and to the presence of one large-bodied species in particular. This suggests that mechanisms behind observed biodiversity effects are the selection effect, which is linked to the occurrence probability of large species, and the complementarity effect, which is driven by functional differentiation among species. Additionally, beetles had significant indirect effects on wood decomposition via bacterial diversity, fungal community composition, and fungal biomass. Our experiment shows that wood decomposition is driven by beetle diversity and its interactions with bacteria and fungi. This highlights that both insect and microbial biodiversity are critical to maintaining ecosystem functioning.

Variation in gene expression along an elevation gradient of Rhododendron sanguineum var. haemaleum assessed in a comparative transcriptomic analysis.

Selection along environmental gradients may play a vital role in driving adaptive evolution. Nevertheless, genomic variation and genetic adaptation along environmental clines remains largely unknown in plants in alpine ecosystems. To close this knowledge gap, we assayed transcriptomic profiles of late flower bud and early leaf bud of Rhododendron sanguineum var. haemaleum from four different elevational belts between 3,000 m and 3,800 m in the Gaoligong Mountains. By comparing differences in gene expression of these samples, a gene co-expression network (WGCNA) was constructed to identify candidate genes related to elevation. We found that the overall gene expression patterns are organ-specific for the flower and leaf. Differentially expressed unigenes were identified in these organs. In flowers, these were mainly related to terpenoid metabolism (RsHMGR, RsTPS), while in leaves mainly related to anthocyanin biosynthesis (RsCHS, RsF3'5'H). Terpenoids are the main components of flower scent (fragrance) likely attracting insects for pollination. In response to fewer pollinators at higher elevation zone, it seems relatively less scent is produced in flower organs to reduce energy consumption. Secondary metabolites in leaves such as anthocyanins determine the plants' alternative adaptive strategy to extreme environments, such as selective pressures of insect herbivory from environmental changes and substrate competition in biosynthesis pathways at high elevations. Our findings indicated that the gene expression profiles generated from flower and leaf organs showed parallel expression shifts but with different functionality, suggesting the existence of flexibility in response strategies of plants exposed to heterogeneous environments across elevational gradients. The genes identified here are likely to be involved in the adaptation of the plants to these varying mountainous environments. This study thus contributes to our understanding of the molecular mechanisms of adaptation in response to environmental change.

A Retrospective Study of Trifluridine/Tipiracil with Fruquintinib in Patients with Chemorefractory Metastatic Colorectal Cancer.

INTRODUCTION: Trifluridine/tipiracil (TAS-102) and fruquintinib are novel antitumor agents for patients with refractory metastatic colorectal cancer (mCRC). We conducted a retrospective study to explore the clinical efficacy and drug toxicities of combination therapy with TAS-102 and fruquintinib in real-life clinical practice. METHODS: Between March 2021 and February 2023, patients at two different centers with mCRC who failed two or more lines of prior therapy and received TAS-102 in combination with fruquintinib were recruited. RESULTS: In total, 32 mCRC patients were included in the analysis. The objective response rate (ORR) and the disease control rate (DCR) were 9.4% and 75%. The median progression-free survival (PFS) and overall survival (OS) were 6.3 (95% CI: 5.3-7.3) and 13.5 (95% CI: 9.5-17.5) months, respectively. Patients without liver metastasis or peritoneal metastasis obtained better median PFS (7.1 m vs. 5.6 m, p = 0.03 and 6.3 m vs. 3.4 m, p = 0.04), and OS (15.2 m vs. 10.4 m, p = 0.01 and 13.6 m vs. 7.1 m, p = 0.03), respectively. Other clinicopathological features, including age, tumor site, KRAS status, dosage of fruquintinib, and treatment line, did not affect the clinical efficacy of TAS-102 combined with fruquintinib. The most common grade three-four toxicities were neutropenia (46.9%), anemia (21.9%), diarrhea (15.6%), nausea (12.5%), and hand-foot syndrome rash (12.5%). CONCLUSIONS: Our results suggest that TAS-102 combined with fruquintinib has promising clinical efficacy and manageable safety for refractory mCRC patients in a real-world clinical setting. Further prospective trials are warranted to confirm our results.

Multitrophic diversity and biotic associations influence subalpine forest ecosystem multifunctionality.

Biodiversity across multiple trophic levels is required to maintain multiple ecosystem functions. Yet it remains unclear how multitrophic diversity and species interactions regulate ecosystem multifunctionality. Here, combining data from 9 different trophic groups (including trees, shrubs, herbs, leaf mites, small mammals, bacteria, pathogenic fungi, saprophytic fungi, and symbiotic fungi) and 13 ecosystem functions related to supporting, provisioning, and regulating services, we used a multitrophic perspective to evaluate the effects of elevation, diversity, and network complexity on scale-dependent subalpine forest multifunctionality. Our results demonstrated that elevation and soil pH significantly modified species composition and richness across multitrophic groups and influenced multiple functions simultaneously. We present evidence that species richness across multiple trophic groups had stronger effects on multifunctionality than species richness at any single trophic level. Moreover, biotic associations, indicating the complexity of trophic networks, were positively associated with multifunctionality. The relative effects of diversity on multifunctionality increased at the scale of the larger community compared to a scale accounting for neighboring interactions. Our results highlight the paramount importance of scale- and context-dependent multitrophic diversity and interactions for a better understanding of mountain ecosystem multifunctionality in a changing world.

Testing genome skimming for species discrimination in the large and taxonomically difficult genus Rhododendron.

Standard plant DNA barcodes based on 2-3 plastid regions, and nrDNA ITS show variable levels of resolution, and fail to discriminate among species in many plant groups. Genome skimming to recover complete plastid genome sequences and nrDNA arrays has been proposed as a solution to address these resolution limitations. However, few studies have empirically tested what gains are achieved in practice. Of particular interest is whether adding substantially more plastid and nrDNA characters will lead to an increase in discriminatory power, or whether the resolution limitations of standard plant barcodes are fundamentally due to plastid genomes and nrDNA not tracking species boundaries. To address this, we used genome skimming to recover near-complete plastid genomes and nuclear ribosomal DNA from Rhododendron species and compared discrimination success with standard plant barcodes. We sampled 218 individuals representing 145 species of this species-rich and taxonomically difficult genus, focusing on the global biodiversity hotspots of the Himalaya-Hengduan Mountains. Only 33% of species were distinguished using ITS+matK+rbcL+trnH-psbA. In contrast, 55% of species were distinguished using plastid genome and nrDNA sequences. The vast majority of this increase is due to the additional plastid characters. Thus, despite previous studies showing an asymptote in discrimination success beyond 3-4 plastid regions, these results show that a demonstrable increase in discriminatory power is possible with extensive plastid genome data. However, despite these gains, many species remain unresolved, and these results also reinforce the need to access multiple unlinked nuclear loci to obtain transformative gains in species discrimination in plants.

Natural hybridization among three Rhododendron species (Ericaceae) revealed by morphological and genomic evidence.

BACKGROUND: Natural hybridization can influence the adaptive response to selection and accelerate species diversification. Understanding the composition and structure of hybrid zones may elucidate patterns of hybridization processes that are important to the formation and maintenance of species, especially for taxa that have experienced rapidly adaptive radiation. Here, we used morphological traits, ddRAD-seq and plastid DNA sequence data to investigate the structure of a Rhododendron hybrid zone and uncover the hybridization patterns among three sympatric and closely related species. RESULTS: Our results show that the hybrid zone is complex, where bi-directional hybridization takes place among the three sympatric parental species: R. spinuliferum, R. scabrifolium, and R. spiciferum. Hybrids between R. spinuliferum and R. spiciferum (R. ×duclouxii) comprise multiple hybrid classes and a high proportion of F1 generation hybrids, while a novel hybrid taxon between R. spinuliferum and R. scabrifolium dominated the F2 generation, but no backcross individuals were detected. The hybrid zone showed basically coincident patterns of population structure between genomic and morphological data. CONCLUSIONS: Natural hybridization exists among the three Rhododendron species in the hybrid zone, although patterns of hybrid formation vary between hybrid taxa, which may result in different evolutionary outcomes. This study represents a unique opportunity to dissect the ecological and evolutionary mechanisms associated with adaptive radiation of Rhododendron species in a biodiversity hotspot.

Fruquintinib beneficial in elderly patient with neoplastic pericardial effusion from rectal cancer: A case report.

BACKGROUND: Neoplastic pericardial effusion (NPE) is a rare consequence of rectal cancer and carries a poor prognosis. Optimal management has yet to be determined. Fruquintinib is an oral anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor approved by the China Food and Drug Administration in September 2018 as third-line treatment of metastatic colorectal cancer. CASE SUMMARY: Herein, we report an elderly patient with NPE from rectal cancer who responded to the use of fruquintinib. In March 2015, a 65-year-old Chinese woman diagnosed with KRAS-mutated adenocarcinoma of the rectum was subjected to proctectomy, adjuvant concurrent chemoradiotherapy, and adjuvant chemotherapy. By October 2018, a mediastinal mass was detected via computed tomography. The growth had invaded parietal pericardium and left hilum, displaying features of rectal adenocarcinoma in a bronchial biopsy. FOLFIRI and FOLFOX chemotherapeutic regimens were administered as first- and second-line treatments. After two cycles of second-line agents, a sizeable pericardial effusion resulting in tamponade was drained by pericardial puncture. Fluid cytology showed cells consistent with rectal adenocarcinoma. Single-agent fruquintinib was initiated on January 3, 2019, as a third-line therapeutic. Ten cycles were delivered before the NPE recurred and other lesions progressed. The recurrence-free interval for NPE was 9.2 mo, attesting to the efficacy of fruquintinib. Ultimately, the patient entered a palliative care unit for best supportive care. CONCLUSION: Fruquintinib may confer good survival benefit in elderly patients with NPEs due to rectal cancer.

Differential expressions of anthocyanin synthesis genes underlie flower color divergence in a sympatric Rhododendron sanguineum complex.

BACKGROUND: The Rhododendron sanguineum complex is endemic to alpine mountains of northwest Yunnan and southeast Tibet of China. Varieties in this complex exhibit distinct flower colors even at the bud stage. However, the underlying molecular regulations for the flower color variation have not been well characterized. Here, we investigated this via measuring flower reflectance profiles and comparative transcriptome analyses on three coexisting varieties of the R. sanguineum complex, with yellow flush pink, bright crimson, and deep blackish crimson flowers respectively. We compared the expression levels of differentially-expressed-genes (DEGs) of the anthocyanin / flavonoid biosynthesis pathway using RNA-seq and qRT-PCR data. We performed clustering analysis based on transcriptome-derived Single Nucleotide Polymorphisms (SNPs) data, and finally analyzed the promoter architecture of DEGs. RESULTS: Reflectance spectra of the three color morphs varied distinctively in the range between 400 and 700 nm, with distinct differences in saturation, brightness, hue, and saturation/hue ratio, an indirect measurement of anthocyanin content. We identified 15,164 orthogroups that were shared among the three varieties. The SNP clustering analysis indicated that the varieties were not monophyletic. A total of 40 paralogous genes encoding 12 enzymes contributed to the flower color polymorphism. These anthocyanin biosynthesis-related genes were associated with synthesis, modification and transportation properties (RsCHS, RsCHI, RsF3H, RsF3'H, RsFLS, RsANS, RsAT, RsOMT, RsGST), as well as genes involved in catabolism and degradation (RsBGLU, RsPER, RsCAD). Variations in sequence and cis-acting elements of these genes might correlate with the anthocyanin accumulation, thus may contribute to the divergence of flower color in the R. sanguineum complex. CONCLUSIONS: Our results suggested that the varieties are very closely related and flower color variations in the R. sanguineum complex correlate tightly with the differential expression levels of genes involved in the anabolic and catabolic synthesis network of anthocyanin. Our study provides a scenario involving intricate relationships between genetic mechanisms for floral coloration accompanied by gene flow among the varieties that may represent an early case of pollinator-mediated incipient sympatric speciation.

Multiple crystal phases of intermetallic tungsten borides and phase-dependent electrocatalytic property for hydrogen evolution.

Four stoichiometric W-B intermetallic phases, including W2B, WB, WB2 and WB3, are synthesized, and their hydrogen-evolution electrocatalytic properties and electronic structures are investigated comparatively. The electrocatalytic activity for the hydrogen evolution reaction is found to first increase from W2B to WB2 and then decrease; and this activity trend can be rationalized based on their different degrees of hybridization between d orbitals of W and sp orbitals of B.

lncRNA OTUD6B-AS1 Exacerbates As2O3-Induced Oxidative Damage in Bladder Cancer via miR-6734-5p-Mediated Functional Inhibition of IDH2.

Arsenic trioxide (As2O3) is a promising effective chemotherapeutic agent for cancer treatment; however, how and through what molecular mechanisms the oxidative damage of As2O3 is controlled remains poorly understood. Recently, the involvement of dysregulated long noncoding RNA ovarian tumor domain containing 6B antisense RNA1 (lncRNA OTUD6B-AS1) in tumorigenesis is established. Here, for the first time, we characterize the regulation of As2O3 in the oxidative damage against bladder cancer via lncRNA OTUD6B-AS1. As2O3 could activate lncRNA OTUD6B-AS1 transcription in bladder cancer cells, and these findings were validated in a xenograft tumor model. Functional assays showed that lncRNA OTUD6B-AS1 dramatically exacerbated As2O3-mediated oxidative damage by inducing oxidative stress. Mechanistically, As2O3 increased levels of metal-regulatory transcription factor 1 (MTF1), which regulates lncRNA OTUD6B-AS1, in response to oxidative stress. Further, lncRNA OTUD6B-AS1 inhibited mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) expression by stabilizing miR-6734-5p, which contributed to cytotoxicity by enhancing oxidative stress. Together, our findings offer new insights into the mechanism of As2O3-induced oxidative damage and identify important factors in the pathway, As2O3/lncRNA OTUD6B-AS1/miR-6734-5p/IDH2, expanding the knowledge of activity of As2O3 as cancer treatment.

Fruquintinib: a novel antivascular endothelial growth factor receptor tyrosine kinase inhibitor for the treatment of metastatic colorectal cancer.

Angiogenesis plays a critical role in the neoplastic growth, progression, and metastasis of colorectal cancer (CRC) in a process regulated by vascular endothelial growth factor (VEGF) family members and their receptors (VEGFR). Several small-molecule anti-VEGFR tyrosine kinase inhibitors (TKIs), such as regorafenib, famitinib, axitinib and apatinib, have been shown to be effective in treating metastatic colorectal cancer (mCRC). Fruquintinib (ELUNATE®) is a novel oral anti-VEGFR TKI, originated and developed by Hutchison MediPharma. Fruquintinib is a potent and highly selective small-molecule inhibitor of VEGFR-1, -2 and -3. In the Phase 3 FRESCO trial, fruquintinib improved both overall survival (OS) and progression-free survival (PFS) in patients with mCRC, compared with placebo. Fruquintinib also showed an acceptable safety and tolerability profile. Based on the data from this trial, fruquintinib was approved by the China Food and Drug Administration (CFDA) in 2018, for the treatment of patients with mCRC who had undergone at least two prior standard anticancer therapies. The existing clinical trials and future prospects of fruquintinib in mCRC will be discussed in this article. In addition, to better understand the role of fruquintinib in this setting, recent advances in other anti-VEGFR TKIs for mCRC treatment are also reviewed herein.

TMEM213 as a novel prognostic and predictive biomarker for patients with lung adenocarcinoma after curative resection: a study based on bioinformatics analysis.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Few effective biomarkers for lung adenocarcinoma have been adapted for clinical practice to assist in prognosis evaluation and treatment plan implementation. Our study's goal was to find a new biological marker associated with the prognosis of lung adenocarcinoma after curative resection and the benefit of adjuvant chemotherapy (ACT). METHODS: Using the clinical information and RNA-Seq expression from The Cancer Genome Atlas (TCGA) database, prognostic genes were screened out and analyzed by Subpopulation Treatment Effect Pattern Plot (STEPP) in GSE42127 to filter out the drug-related gene. The relationship between the gene expression and clinicopathological parameters was assessed in the TCGA database. The prognostic significance was evaluated by Cox proportional hazards (PHs) regression analysis with 1,000 bootstrap replications. Gene set enrichment analysis (GSEA) was performed using high-throughput RNA sequencing data in TCGA and functional gene sets derived from the Molecular Signatures Database (MSigDB). RESULTS: A total of 297 prognostic genes were analyzed by STEPP in GSE42127. The results indicated a beneficial effect of adjuvant paclitaxel-carboplatin in patients with high TMEM213 expression. Its expression correlated with gender (P=0.013), and Kaplan-Meier analysis showed that patients with high TMEM213 expression had significantly longer overall survival (OS) (P=0.014, 0.027, and 0.000). Multivariate analysis showed TMEM213 to be an independent predictor for improved OS of patients (P=0.020), and the result was verified with the bootstrapping methodology and online "Kaplan-Meier Plotter" database analysis. Moreover, enriched pathway analysis indicated that TMEM213 expression was associated with the two gene sets of KEGG_DRUG_METABOLISM_CYTOCHROME_P450 and KEGG_ABC_TRANSPORTERS. CONCLUSIONS: Based on bioinformatics analysis, we found that TMEM213 expression independently predicted better OS for lung adenocarcinoma. Patients in the high TMEM213 group appear to benefit more from adjuvant paclitaxel-carboplatin, but this needs further validation.

Greater than the sum of the parts: how the species composition in different forest strata influence ecosystem function.

The mechanisms underpinning forest biodiversity-ecosystem function relationships remain unresolved. Yet, in heterogeneous forests, ecosystem function of different strata could be associated with traits or evolutionary relationships differently. Here, we integrate phylogenies and traits to evaluate the effects of elevational diversity on above-ground biomass across forest strata and spatial scales. Community-weighted means of height and leaf phosphorous concentration and functional diversity in specific leaf area exhibited positive correlations with tree biomass, suggesting that both positive selection effects and complementarity occur. However, high shrub biomass is associated with greater dissimilarity in seed mass and multidimensional trait space, while species richness or phylogenetic diversity is the most important predictor for herbaceous biomass, indicating that species complementarity is especially important for understory function. The strength of diversity-biomass relationships increases at larger spatial scales. We conclude that strata- and scale- dependent assessments of community structure and function are needed to fully understand how biodiversity influences ecosystem function.

Development of polymorphic microsatellite markers for tree peony Paeonia delavayi (Paeoniaceae) using ddRAD-seq data.

Microsatellite markers were developed for the tree peony Paeonia delavayi to investigate fine scale population genetics of this species. Using ddRAD-seq data from twenty individuals of P. delavayi, we identified 529 polymorphic microsatellite loci, of which 195 were suitable for designing microsatellite primers. Of the 120 microsatellite loci selected for validation, 20 were successfully amplified with clear peaks and displayed polymorphism. Three populations were genotyped using the 20 polymorphic microsatellites. The number of alleles per locus ranged from two to thirteen. Observed and expected heterozygosity ranged from 0 to 0.941 and 0 to 0.834 respectively. The cross-species amplification test using five individuals from a population of P. ludlowii showed that 15 of the 20 polymorphic loci were successfully amplified, and four loci showed polymorphism. Among the 22 alleles occurring in P. ludlowii across fifteen loci, eight alleles across five loci were exclusive to P. ludlowii. The results demonstrate that ddRAD-seq is an efficient method for the development of microsatellite markers for non-model organisms with large genomes. The newly developed markers will be valuable tools to investigate the genetic diversity, genetic structure, and gene flow of P. delavayi from local to regional spatial scales.

Significant benefit of Nivolumab treating PD-L1 positive metastatic pulmonary carcinosarcoma: a case report and literature review.

Immunotherapy has recently become a new focus for the treatment of malignant tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its ligand (PD-L1), restoring the immune response of T cells, and enhancing the recognition of tumor cells by the immune system. Pulmonary carcinosarcoma is an uncommon but highly aggressive tumor type with a poor prognosis. We described a case of pulmonary carcinosarcoma, with the positive expression of PD-L1, obtained a significant benefit from Nivolumab treatment in a 64-year-old Chinese man, which give us a clue that patients with pulmonary carcinosarcoma may benefit fromanti-PD-1 immunotherapy.

Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway.

BACKGROUND AND AIM: Recent investigation revealed that dysbiosis in the gut flora and disruption of permeability of intestinal barrier are possible causes for the development of autoimmune hepatitis. Supplementation of sodium butyrate has been suggested to protect liver injury from disrupted permeability of small intestine. In current study, we employed S100/Freund's complete adjuvant induced autoimmune hepatitis to investigate therapeutic efficacy of sodium butyrate and its mechanism in the liver and upper small intestine. METHODS: C57BL/6 mice were employed and divided into three groups - control group (n=8), autoimmune hepatitis group (n=12) and autoimmune hepatitis with treatment of sodium butyrate group (n=12). Histological staining and western blot analyses were employed to evaluate liver and upper small intestine morphology and gene expression respectively. RESULTS: The findings revealed that S100/Freund's complete adjuvant caused liver injury and disruption of upper small intestine villi. Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver. Moreover, the effect of sodium butyrate on protection of injuries of the liver and upper small intestine could be due to inhibition of toll-like receptor 4 signaling pathway, as well as its down-regulation of inflammatory cytokines - interleukin-6 and tumor necrosis factor-a. CONCLUSIONS: Sodium butyrate can prevent liver injury by maintaining the integrity of small intestine and inhibiting inflammatory response in S100/Freund's complete adjuvant induced autoimmune hepatitis.