Gut fungi of black-necked cranes (Grus nigricollis) respond to dietary changes during wintering.

BACKGROUND: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). RESULTS: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. CONCLUSIONS: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

Application of artificial intelligence-based dual source CT scanning in the differentiation of lung adenocarcinoma in situ and minimally invasive adenocarcinoma.

Background and Objective: Lung adenocarcinoma is the most common type of lung cancer with highly incidence and mortality. Due to the overlap of morphological features, it is difficult to distinguish clinically between preinvasive lesions (in situ adenocarcinoma, AIS) and invasive lesions (minimally invasive adenocarcinoma, MIA), which appear as ground glass cloudy nodules. This study was performed to probe the application value of artificial intelligence (AI)-based dual source CT scanning in the differentiation of AIS as well as MIA. Methods: The clinical data of 136 patients in Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to January 2022 were retrospectively analyzed. The accuracy of AI in distinguishing lung AIS (n=76) and MIA (n=60) were analyzed. The effectiveness of AI in detecting nodules and its diagnostic efficacy for AIS and MIA were explored. Results: The proportion of patients with clear and regular lesion boundaries in AIS was higher than that in MIA. The mean lesion diameter of AIS patients was shorter than MIA patients. There was no difference in the CT value between AIS and MIA in the ground glass nodule density area of pure ground glass nodule and mixed ground glass nodule, but the CT value of the solid nodule density area in AIS was lower. The occurrence of pulmonary vascular abnormality, air bronchogram sign, and pleural depression in AIS patients were lower than MIA patients. The detection rate of AI for lung adenocarcinoma with nodule diameter ≤ 5 mm, complete solid nodules and ground glass nodules was significantly higher than radiologists. The sensitivity, specificity, positive prediction rate, negative prediction rate and accuracy of AI detection were significantly higher than radiologists. Conclusion: AI-based dual source CT scanning can clearly show the morphological characteristics of lung adenocarcinoma, which is helpful for the differential diagnosis of lung AIS as well as MIA.

Gut microbiota enhance energy accumulation of black-necked crane to cope with impending migration.

Less is known about the role of gut microbiota in overwintering environmental adaptation in migratory birds. Here, we performed metagenomic sequencing on fresh fecal samples (n = 24) collected during 4 periods of overwintering (Dec: early; Jan: middle I; Feb: middle II; Mar: late) to characterize gut microbial taxonomic and functional characteristics of black-necked crane (Grus nigricollis). The results demonstrated no significant change in microbial diversity among overwintering periods. Analysis of compositions of microbiomes with bias correction (ANCOM-BC) determined 15 Proteobacteria species enriched in late overwintering period. Based on previous reports, these species are associated with degradation of chitin, cellulose, and lipids. Meanwhile, fatty acid degradation and betalain biosynthesis pathways are enriched in late overwintering period. Furthermore, metagenomic binning obtained 91 high-quality bins (completeness >70% and contamination <10%), 5 of which enriched in late overwintering period. Carnobacterium maltaromaticum, unknown Enterobacteriaceae, and Yersinia frederiksenii have genes for chitin and cellulose degradation, acetate, and glutamate production. Unknown Enterobacteriaceae and Y. frederiksenii hold genes for synthesis of 10 essential amino acids required by birds, and the latter has genes for γ-aminobutyrate production. C. maltaromaticum has genes for pyridoxal synthesis. These results implied the gut microbiota is adapted to the host diet and may help black-necked cranes in pre-migratory energy accumulation by degrading the complex polysaccharide in their diet, supplying essential amino acids and vitamin pyridoxal, and producing acetate, glutamate, and γ-aminobutyrate that could stimulate host feeding. Additionally, enriched Proteobacteria also encoded more carbohydrate-active enzymes (CAZymes) and antibiotic resistance genes (ARGs) in late overwintering period. KEY POINTS: • Differences in gut microbiota function during overwintering period of black-necked cranes depend mainly on changes in core microbiota abundance • Gut microbiota of black-necked crane adapted to the diet during overwintering period • Gut microbiota could help black-necked cranes to accumulate more energy in the late overwintering period.

LncRNA H19 Regulates Breast Cancer DNA Damage Response and Sensitivity to PARP Inhibitors via Binding to ILF2.

Although DNA damage repair plays a critical role in cancer chemotherapy, the function of lncRNAs in this process remains largely unclear. In this study, in silico screening identified H19 as an lncRNA that potentially plays a role in DNA damage response and sensitivity to PARP inhibitors. Increased expression of H19 is correlated with disease progression and with a poor prognosis in breast cancer. In breast cancer cells, forced expression of H19 promotes DNA damage repair and resistance to PARP inhibition, whereas H19 depletion diminishes DNA damage repair and increases sensitivity to PARP inhibitors. H19 exerted its functional roles via direct interaction with ILF2 in the cell nucleus. H19 and ILF2 increased BRCA1 stability via the ubiquitin-proteasome proteolytic pathway via the H19- and ILF2-regulated BRCA1 ubiquitin ligases HUWE1 and UBE2T. In summary, this study has identified a novel mechanism to promote BRCA1-deficiency in breast cancer cells. Therefore, targeting the H19/ILF2/BRCA1 axis might modulate therapeutic approaches in breast cancer.

Critical Role of Removing Impurities in Nickel Oxide on High-Efficiency and Long-Term Stability of Inverted Perovskite Solar Cells.

The performance enhancement of inverted perovskite solar cells applying nickel oxide (NiOx ) as the hole transport layer (HTL) has been limited by impurity ions (such as nitrate ions). Herein, we have proposed a strategy to obtain high-quality NiOx nanoparticles via an ionic liquid-assisted synthesis method (NiOx -IL). Experimental and theoretical results illustrate that the cation of the ionic liquid can inhibit the adsorption of impurity ions on nickel hydroxide through a strong hydrogen bond and low adsorption energy, thereby obtaining NiOx -IL HTL with high conductivity and strong hole-extraction ability. Importantly, the removal of impurity ions can effectively suppress the redox reaction between the NiOx film and the perovskite film, thus slowing down the deterioration of device performance. Consequently, the modified inverted device shows a striking efficiency exceeding 22.62 %, and superior stability maintaining 92 % efficiency at a maximum power point tracking under one sun illumination for 1000 h.

Structural changes in the gut microbiota community of the black-necked crane (Grus nigricollis) in the wintering period.

During overwintering of black-necked cranes (Grus nigricollis), the composition and function of the gut microbiota changes are of considerable interest for understanding its environmental adaption mechanism. In this study, we characterized the structure of the gut microbiota from the black-necked crane in the Dashanbao wintering area, and compared the early-winter (November) microbiota to the late-winter (March of the next year) microbiota. The results showed that the gut microbiota diversity of black-necked crane in the early-overwintering stage was higher than that in the late-overwintering stage, but it did not reach a significant level. Gut microbiota taxonomic composition analysis showed that relative abundance of Bacteroidota increased significantly, and showed decreased Firmicutes to Bacteroidota ratio at the phylum level, meanwhile, the abundance of Lactobacillus decreased significantly at the genus level. Explain gut microbiota between the early- and late-wintering showed some differences in microbiota richness but maintained a relatively conservative microbiota structure. PICRUSt2 method was used to predict and analyze the KEGG functional abundance of 16S rDNA sequences of bacteria, it was found that the changes in gut microbiota composition increased the abundance of bacteria associated with amino acid biosynthesis and acid metabolism in the late stage of overwintering. This work provides basic data for black-necked crane gut microbiota study, which might further contribute to their protection.

Post-transcriptional regulation of ERBB2 by miR26a/b and HuR confers resistance to tamoxifen in estrogen receptor-positive breast cancer cells.

Tamoxifen-resistant (TAMR) estrogen receptor-positive (ER+) breast cancer is characterized by elevated Erb-B2 receptor tyrosine kinase 2 (ERBB2) expression. However, the underlying mechanisms responsible for the increased ERBB2 expression in the TAMR cells remain poorly understood. Herein, we reported that the ERBB2 expression is regulated at the post-transcriptional level by miR26a/b and the RNA-binding protein human antigen R (HuR), both of which associate with the 3'-UTR of the ERBB2 transcripts. We demonstrated that miR26a/b inhibits the translation of ERBB2 mRNA, whereas HuR enhances the stability of the ERBB2 mRNA. In TAMR ER+ breast cancer cells with elevated ERBB2 expression, we observed a decrease in the level of miR26a/b and an increase in the level of HuR. The forced expression of miR26a/b or the depletion of HuR decreased ERBB2 expression in the TAMR cells, resulting in the reversal of tamoxifen resistance. In contrast, the inactivation of miR26a/b or forced expression of HuR decreased tamoxifen responsiveness of the parental ER+ breast cancer cells. We further showed that the increase in HuR expression in the TAMR ER+ breast cancer cells is attributable to an increase in the HuR mRNA isoform with shortened 3'-UTR, which exhibits increased translational activity. This shortening of the HuR mRNA 3'-UTR via alternative polyadenylation (APA) was observed to be dependent on cleavage stimulation factor subunit 2 (CSTF2/CstF-64), which is up-regulated in the TAMR breast cancer cells. Taken together, we have characterized a model in which the interplay between miR26a/b and HuR post-transcriptionally up-regulates ERBB2 expression in TAMR ER+ breast cancer cells.

Characterization of the Gut Microbiota in Six Geographical Populations of Chinese Rhesus Macaques (Macaca mulatta), Implying an Adaptation to High-Altitude Environment.

Knowledge about the impact of different geographical environments on rhesus macaque gut microbiota is limited. In this study, we compared the characteristics of gut microbiota in six different Chinese rhesus macaque populations, including Hainan, Nanning, Guizhou, Xichang, Jianchuan and Tibet. Through the composition analysis of operational taxonomic units (OTUs), we found that there were significant differences in the abundance of core overlapping OTUs in the six Chinese groups. Specifically, the Tibet population exhibited the highest gut microbial diversity and the most unique OTUs. Statistically significant differences in the composition of gut microbiota among the six groups at phylum and family level were evident. Specifically, Tibet had higher abundances of Firmicutes and lower abundances of Bacteroidetes than the other geographical groups, and the higher abundance of Firmicutes in the Tibetan group was mainly caused by a significant increase in the family Ruminococcaceae and Christensenellaceae. Phylogenetic investigation of communities by reconstruction of unobserved state analysis showed that the enrichment ratio for environmental information processing and organismal systems was the highest in the Tibet population. Additionally, our results suggested that in the adaptation process of rhesus macaques to different geographical environments, the abundance of the core common flora of the intestinal microbes had undergone varying degree of change and produced new and unique flora, both of which helped to reshape the gut microbiota of rhesus macaques. In particular, this change was more obvious for animals in the high-altitude environments.

Many private mutations originate from the first few divisions of a human colorectal adenoma.

Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. Here we find that ITH can be remarkably well structured by measuring point mutations, chromosome copy numbers, and DNA passenger methylation from opposite sides and individual glands of a 6 cm human colorectal adenoma. ITH was present between tumour sides and individual glands, but the private mutations were side-specific and subdivided the adenoma into two major subclones. Furthermore, ITH disappeared within individual glands because the glands were clonal populations composed of cells with identical mutant genotypes. Despite mutation clonality, the glands were relatively old, diverse populations when their individual cells were compared for passenger methylation and by FISH. These observations can be organized into an expanding star-like ancestral tree with co-clonal expansion, where many private mutations and multiple related clones arise during the first few divisions. As a consequence, most detectable mutational ITH in the final tumour originates from the first few divisions. Much of the early history of a tumour, especially the first few divisions, may be embedded within the detectable ITH of tumour genomes.

Artemin, a member of the glial cell line-derived neurotrophic factor family of ligands, is HER2-regulated and mediates acquired trastuzumab resistance by promoting cancer stem cell-like behavior in mammary carcinoma cells.

Previous studies have demonstrated that Artemin (ARTN) functions as a cancer stem cell (CSC) and metastatic factor in mammary carcinoma. Herein, we report that ARTN mediates acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells. Ligands that increase HER2 activity increased ARTN expression in HER2-positive mammary carcinoma cells, whereas trastuzumab inhibited ARTN expression. Forced expression of ARTN decreased the sensitivity of HER2-positive mammary carcinoma cells to trastuzumab both in vitro and in vivo. Conversely, siRNA-mediated depletion of ARTN enhanced trastuzumab efficacy. Cells with acquired resistance to trastuzumab exhibited increased ARTN expression, the depletion of which restored trastuzumab sensitivity. Trastuzumab resistance produced an increased CSC population concomitant with enhanced mammospheric growth. ARTN mediated the enhancement of the CSC population by increased BCL-2 expression, and the CSC population in trastuzumab-resistant cells was abrogated upon inhibition of BCL-2. Hence, we conclude that ARTN is one mediator of acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells.

Ancestral inference in tumors: how much can we know?

A tumor is thought to start from a single cell and genome. Yet genomes in the final tumor are typically heterogeneous. The mystery of this intratumoral heterogeneity (ITH) has not yet been uncovered, but much of this ITH may be secondary to replication errors. Methylation of cytosine bases often exhibits ITH and therefore may encode the ancestry of the tumor. In this study, we measure the passenger methylation patterns of a specific CpG region in 9 colorectal tumors by bisulfite sequencing and apply a tumor development model. Based on our model, we are able to retrieve information regarding the ancestry of each tumor using approximate Bayesian computation. With a large simulation study we explore the conditions under which we can estimate the model parameters, and the initial state of the first transformed cell. Finally we apply our analysis to clinical data to gain insight into the dynamics of tumor formation.

Metabarcoding of protozoa and helminth in black-necked cranes: a high prevalence of parasites and free-living amoebae.

Parasites and free-living amoebae (FLA) are common pathogens that pose threats to wildlife and humans. The black-necked crane (Grus nigricollis) is a near-threatened species and there is a shortage of research on its parasite diversity. Our study aimed to use noninvasive methods to detect intestinal parasites and pathogenic FLA in G. nigricollis using high-throughput sequencing (HTS) based on the 18S rDNA V9 region. A total of 38 fresh fecal samples were collected in Dashanbao, China, during the overwintering period (early-, middle I-, middle II-, and late-winter). Based on the 18S data, eight genera of parasites were identified, including three protozoan parasites: Eimeria sp. (92.1%) was the dominant parasite, followed by Tetratrichomonas sp. (36.8%) and Theileria sp. (2.6%). Five genera of helminths were found: Echinostoma sp. (100%), Posthodiplostomum sp. (50.0%), Euryhelmis sp. (26.3%), Eucoleus sp. (50.0%), and Halomonhystera sp. (2.6%). Additionally, eight genera of FLA were detected, including the known pathogens Acanthamoeba spp. (n = 13) and Allovahlkampfia spp. (n = 3). Specific PCRs were used to further identify the species of some parasites and FLA. Furthermore, the 18S data indicated significant changes in the relative abundance and genus diversity of the protozoan parasites and FLA among the four periods. These results underscore the importance of long-term monitoring of pathogens in black-necked cranes to protect this near-endangered species.

Title: Métabarcoding des protozoaires et des helminthes chez les grues à cou noir : forte prévalence de parasites et d'amibes libres. Abstract: Les parasites et les amibes libres sont des agents pathogènes courants qui constituent une menace pour la faune et les humains. La grue à cou noir (Grus nigricollis) est une espèce quasi menacée et les recherches sur sa diversité parasitaire sont insuffisantes. Notre étude visait à utiliser des méthodes non invasives pour détecter les parasites intestinaux et les amibes libres pathogènes chez G. nigricollis en utilisant le séquençage à haut débit basé sur la région V9 de l'ADNr 18S. Au total, 38 échantillons de matières fécales fraîches ont été collectés à Dashanbao, en Chine, au cours de la période d'hivernage (début, milieu I, milieu II et fin de l'hiver). Sur la base des données 18S, huit genres de parasites ont été identifiés, dont trois parasites protozoaires : Eimeria sp. (92,1 %) était le parasite dominant, suivi de Tetratrichomonas sp. (36,8 %) et Theileria sp. (2,6 %). Cinq genres d'helminthes ont été trouvés : Echinostoma sp. (100 %), Posthodiplostomum sp. (50,0 %), Euryhelmis sp. (26,3 %), Eucoleus sp. (50,0 %) et Halomonhystera sp. (2,6 %). De plus, huit genres d'amibes libres ont été détectés, y compris les agents pathogènes connus Acanthamoeba spp. (n = 13) et Allovahlkampfia spp. (n = 3). Des PCR spécifiques ont été utilisées pour identifier davantage les espèces de certains parasites et amibes libres. En outre, les données 18S ont indiqué des changements significatifs dans l'abondance relative et la diversité des genres des parasites protozoaires et des amibes au cours des quatre périodes. Ces résultats soulignent l'importance de la surveillance à long terme des agents pathogènes chez les grues à cou noir pour protéger cette espèce quasi menacée.

Diverse captive non-human primates with phytanic acid-deficient diets rich in plant products have substantial phytanic acid levels in their red blood cells.

BACKGROUND: Humans and rodents with impaired phytanic acid (PA) metabolism can accumulate toxic stores of PA that have deleterious effects on multiple organ systems. Ruminants and certain fish obtain PA from the microbial degradation of dietary chlorophyll and/or through chlorophyll-derived precursors. In contrast, humans cannot derive PA from chlorophyll and instead normally obtain it only from meat, dairy, and fish products. RESULTS: Captive apes and Old world monkeys had significantly higher red blood cell (RBC) PA levels relative to humans when all subjects were fed PA-deficient diets. Given the adverse health effects resulting from PA over accumulation, we investigated the molecular evolution of thirteen PA metabolism genes in apes, Old world monkeys, and New world monkeys. All non-human primate (NHP) orthologs are predicted to encode full-length proteins with the marmoset Phyh gene containing a rare, but functional, GA splice donor dinucleotide. Acox2, Scp2, and Pecr sequences had amino acid positions with accelerated substitution rates while Amacr had significant variation in evolutionary rates in apes relative to other primates. CONCLUSIONS: Unlike humans, diverse captive NHPs with PA-deficient diets rich in plant products have substantial RBC PA levels. The favored hypothesis is that NHPs can derive significant amounts of PA from the degradation of ingested chlorophyll through gut fermentation. If correct, this raises the possibility that RBC PA levels could serve as a biomarker for evaluating the digestive health of captive NHPs. Furthermore, the evolutionary rates of the several genes relevant to PA metabolism provide candidate genetic adaptations to NHP diets.

Diet and high altitude strongly drive convergent adaptation of gut microbiota in wild macaques, humans, and dogs to high altitude environments.

Animal gut microbiota plays an indispensable role in host adaptation to different altitude environments. At present, little is known about the mechanism of animal gut microbiota in host adaptation to high altitude environments. Here, we selected wild macaques, humans, and dogs with different levels of kinship and intimate relationships in high altitude and low altitude environments, and analyzed the response of their gut microbiota to the host diet and altitude environments. Alpha diversity analysis found that at high altitude, the gut microbiota diversity of wild macaques with more complex diet in the wild environments is much higher than that of humans and dogs with simpler diet (p < 0.05), and beta diversity analysis found that the UniFrac distance between humans and dogs was significantly lower than between humans and macaques (p < 0.05), indicating that diet strongly drive the convergence of gut microbiota among species. Meanwhile, alpha diversity analysis found that among three subjects, the gut microbiota diversity of high altitude population is higher than that of low altitude population (ACE index in three species, Shannon index in dog and macaque and Simpson index in dog, p < 0.05), and beta diversity analysis found that the UniFrac distances among the three subjects in the high altitude environments were significantly lower than in the low altitude environments (p < 0.05). Additionally, core shared ASVs analysis found that among three subjects, the number of core microbiota in high altitude environments is higher than in low altitude environments, up to 5.34 times (1,105/207), and the proportion and relative abundance of the core bacteria types in each species were significantly higher in high altitude environments than in low altitude environments (p < 0.05). The results showed that high altitude environments played an important role in driving the convergence of gut microbiota among species. Furthermore, the neutral community model trial found that the gut microbiota of the three subjects was dispersed much more at high altitude than at low altitude, implying that the gut microbiota convergence of animals at high altitudes may be partly due to the microbial transmission between hosts mediated by human activities.

Room temperature nondestructive encapsulation via self-crosslinked fluorosilicone polymer enables damp heat-stable sustainable perovskite solar cells.

Encapsulation engineering is an effective strategy to improve the stability of perovskite solar cells. However, current encapsulation materials are not suitable for lead-based devices because of their complex encapsulation processes, poor thermal management, and inefficient lead leakage suppression. In this work, we design a self-crosslinked fluorosilicone polymer gel, achieving nondestructive encapsulation at room temperature. Moreover, the proposed encapsulation strategy effectively promotes heat transfer and mitigates the potential impact of heat accumulation. As a result, the encapsulated devices maintain 98% of the normalized power conversion efficiency after 1000 h in the damp heat test and retain 95% of the normalized efficiency after 220 cycles in the thermal cycling test, satisfying the requirements of the International Electrotechnical Commission 61215 standard. The encapsulated devices also exhibit excellent lead leakage inhibition rates, 99% in the rain test and 98% in the immersion test, owing to excellent glass protection and strong coordination interaction. Our strategy provides a universal and integrated solution for achieving efficient, stable, and sustainable perovskite photovoltaics.

Metagenome and metabolome insights into the energy compensation and exogenous toxin degradation of gut microbiota in high-altitude rhesus macaques (Macaca mulatta).

There have been many reports on the genetic mechanism in rhesus macaques (RMs) for environmental adaptation to high altitudes, but the synergistic involvement of gut microbiota in this adaptation remains unclear. Here we performed fecal metagenomic and metabolomic studies on samples from high- and low-altitude populations to assess the synergistic role of gut microbiota in the adaptation of RMs to high-altitude environments. Microbiota taxonomic annotation yielded 7471 microbiota species. There were 37 bacterial species whose abundance was significantly enriched in the high-altitude populations, 16 of which were previously reported to be related to the host's dietary digestion and energy metabolism. Further functional gene enrichment found a stronger potential for gut microbiota to synthesize energy substrate acetyl-CoA using CO2 and energy substrate pyruvate using oxaloacetate, as well as a stronger potential to transform acetyl-CoA to energy substrate acetate in high-altitude populations. Interestingly, there were no apparent differences between low-altitude and high-altitude populations in terms of genes enriched in the main pathways by which the microbiota consumed the three energy substrates, and none of the three energy substrates were detected in the fecal metabolites. These results strongly suggest that gut microbiota plays an important energy compensatory role that helps RMs to adapt to high-altitude environments. Further functional enrichment after metabolite source analysis indicated the abundance of metabolites related to the degradation of exogenous toxins was also significantly higher in high-altitude populations, which suggested a contributory role of gut microbiota to the degradation of exogenous toxins in wild RMs adapted to high-altitude environments.

Directed Nickel-Catalyzed Diastereoselective Reductive Difunctionalization of Alkenyl Amines.

We report herein an intermolecular syn-arylalkylation and alkenylalkylation of alkenyl amines with two different organohalides (iodides and bromides) using Ni(II) catalyst. The cleavable bidentate quinolinamide is utilized after extensive directing group screening to enable olefin difunctionalization with high levels of regio-, chemo-, and diastereocontrol. This general and practical protocol is compatible with α- or ß-substituted terminal alkenes and internal alkenes, providing rapid access to branched aliphatic amines bearing two skipped and vicinal stereocenters with high diastereoselectivities that would otherwise be difficult to synthesize.

Efficient and stable inverted perovskite solar cells with very high fill factors via incorporation of star-shaped polymer.

Stabilizing high-efficiency perovskite solar cells (PSCs) at operating conditions remains an unresolved issue hampering its large-scale commercial deployment. Here, we report a star-shaped polymer to improve charge transport and inhibit ion migration at the perovskite interface. The incorporation of multiple chemical anchor sites in the star-shaped polymer branches strongly controls the crystallization of perovskite film with lower trap density and higher carrier mobility and thus inhibits the nonradiative recombination and reduces the charge-transport loss. Consequently, the modified inverted PSCs show an optimal power conversion efficiency of 22.1% and a very high fill factor (FF) of 0.862, corresponding to 95.4% of the Shockley-Queisser limited FF (0.904) of PSCs with a 1.59-eV bandgap. The modified devices exhibit excellent long-term operational and thermal stability at the maximum power point for 1000 hours at 45°C under continuous one-sun illumination without any significant loss of efficiency.

Synergistic Effect through the Introduction of Inorganic Zinc Halides at the Interface of TiO2 and Sb2S3 for High-Performance Sb2S3 Planar Thin-Film Solar Cells.

The competition between charge recombination and extraction principally affects the fill factor (FF) and power conversion efficiency (PCE) of planar thin-film solar cells. In Sb2S3 thin-film solar cells, the electrocharge recombination and extraction n transport layer (ETL) plays a significant role in electron extraction and determination of Sb2S3 film absorber quality. Herein, a TiO2 ETL is strategically modified using an inorganic salt zinc halide (i.e., ZnCl2, ZnBr2, ZnI2), which simultaneously improves the electronic properties of TiO2 and promotes the growth of Sb2S3 films with larger grain size and higher crystallinity. The experimental results and theoretical calculations further reveal that the zinc halide can interact with TiO2 and simultaneously bond strongly with the upper Sb2S3 film, which creates a unique pathway for electron transfer, passivates the trap states, and alleviates the recombination losses effectively. As a result, an average PCE of 6.87 ± 0.11% and the highest PCE of 7.08% have been attained with an improved FF from 51.22 to 61.61% after ZnCl2 introduction. Additionally, introduction of ZnCl2 helps the unencapsulated devices to maintain 93% of their original performance after 2400 h of storage in a nitrogen-filled glovebox. This work develops an effective route for the optimization of ETLs and defect healing using simple and low-cost inorganic salts.

NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression.

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and involved in many diseases, including cancer. CFIm25, a subunit of the cleavage factor I encoded by NUDT21, is required for 3'RNA cleavage and polyadenylation. Although it has been recently reported to be involved in glioblastoma tumor suppression, its roles and the underlying functional mechanism remain unclear in other types of cancer. In this study, we characterized NUDT21 in hepatocellular carcinoma (HCC). Reduced expression of NUDT21 was observed in HCC tissue compared to adjacent non-tumorous compartment. HCC patients with lower NUDT21 expression have shorter overall and disease-free survival times than those with higher NUDT21 expression after surgery. Knockdown of NUDT21 promotes HCC cell proliferation, metastasis, and tumorigenesis, whereas forced expression of NUDT21 exhibits the opposite effects. We then performed global APA site profiling analysis in HCC cells and identified considerable number of genes with shortened 3'UTRs upon the modulation of NUDT21 expression. In particular, we further characterized the NUDT21-regulated genes PSMB2 and CXXC5. We found NUDT21 knockdown increases usage of the proximal polyadenylation site in the PSMB2 and CXXC5 3' UTRs, resulting in marked increase in the expression of PSMB2 and CXXC5. Moreover, knockdown of PSMB2 or CXXC5 suppresses HCC cell proliferation and invasion. Taken together, our study demonstrated that NUDT21 inhibits HCC proliferation, metastasis and tumorigenesis, at least in part, by suppressing PSMB2 and CXXC5, and thereby provided a new insight into understanding the connection of HCC suppression and APA machinery.