A point mutation in the meiotic crossover formation gene HEI10/TFS2 leads to thermosensitive genic sterility in rice.

Thermosensitive genic female sterility (TGFS) is a promising property to be utilized for hybrid breeding. Here, we identified a rice TGFS line, tfs2, through an ethyl methyl sulfone (EMS) mutagenesis strategy. This line showed sterility under high temperature and became fertile under low temperature. Few seeds were produced when the tfs2 stigma was pollinated, indicating that tfs2 is female sterile. Gene cloning and genetic complementation showed that a point mutation from leucine to phenylalanine in HEI10 (HEI10tfs2), a crossover formation protein, caused the TGFS trait of tfs2. Under high temperature, abnormal univalents were formed, and the chromosomes were unequally segregated during meiosis, similar to the reported meiotic defects in oshei10. Under low temperature, the number of univalents was largely reduced, and the chromosomes segregated equally, suggesting that crossover formation was restored in tfs2. Yeast two-hybrid assays showed that HEI10 interacted with two putative protein degradation-related proteins, RPT4 and SRFP1. Through transient expression in tobacco leaves, HEI10 were found to spontaneously aggregate into dot-like foci in the nucleus under high temperature, but HEI10tfs2 failed to aggregate. In contrast, low temperature promoted HEI10tfs2 aggregation. This result suggests that protein aggregation at the crossover position contributes to the fertility restoration of tfs2 under low temperature. In addition, RPT4 and SRFP1 also aggregated into dot-like foci, and these aggregations depend on the presence of HEI10. These findings reveal a novel mechanism of fertility restoration and facilitate further understanding of HEI10 in meiotic crossover formation.

Temperature and light reverse the fertility of rice P/TGMS line ostms19 via reactive oxygen species homeostasis.

P/TGMS (Photo/thermo-sensitive genic male sterile) lines are crucial resources for two-line hybrid rice breeding. Previous studies revealed that slow development is a general mechanism for sterility-fertility conversion of P/TGMS in Arabidopsis. However, the difference in P/TGMS genes between rice and Arabidopsis suggests the presence of a distinct P/TGMS mechanism in rice. In this study, we isolated a novel P/TGMS line, ostms19, which shows sterility under high-temperature conditions and fertility under low-temperature conditions. OsTMS19 encodes a novel pentatricopeptide repeat (PPR) protein essential for pollen formation, in which a point mutation GTA(Val) to GCA(Ala) leads to ostms19 P/TGMS phenotype. It is highly expressed in the tapetum and localized to mitochondria. Under high temperature or long-day photoperiod conditions, excessive ROS accumulation in ostms19 anthers during pollen mitosis disrupts gene expression and intine formation, causing male sterility. Conversely, under low temperature or short-day photoperiod conditions, ROS can be effectively scavenged in anthers, resulting in fertility restoration. This indicates that ROS homeostasis is critical for fertility conversion. This relationship between ROS homeostasis and fertility conversion has also been observed in other tested rice P/TGMS lines. Therefore, we propose that ROS homeostasis is a general mechanism for the sterility-fertility conversion of rice P/TGMS lines.

Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.

Methadone is cleared predominately by hepatic cytochrome P450 (CYP) 2B6-catalyzed metabolism to inactive metabolites. CYP2B6 also catalyzes the metabolism of several other drugs. Methadone and CYP2B6 are susceptible to pharmacokinetic drug-drug interactions. Use of natural products such as herbals and other botanicals is substantial and growing, and concomitant use of prescription medicines and non-prescription herbals is common and may result in interactions, often precipitated by CYP inhibition. Little is known about herbal product effects on CYP2B6 activity, and CYP2B6-catalyzed methadone metabolism. We screened a family of natural product compounds used in traditional medicines, herbal teas, and synthetic analogs of compounds found in plants, including kavalactones, flavokavains, chalcones and gambogic acid, for inhibition of expressed CYP2B6 activity and specifically inhibition of CYP2B6-mediated methadone metabolism. An initial screen evaluated inhibition of CYP2B6-catalyzed 7-ethoxy-4-(trifluoromethyl) coumarin O-deethylation. Hits were further evaluated for inhibition of racemic methadone metabolism, including mechanism of inhibition and kinetic constants. In order of decreasing potency, the most effective inhibitors of methadone metabolism were dihydromethysticin (competitive, K i 0.074 µM), gambogic acid (noncompetitive, K i 6 µM), and 2,2'-dihydroxychalcone (noncompetitive, K i 16 µM). Molecular modeling of CYP2B6-methadone and inhibitor binding showed substrate and inhibitor binding position and orientation and their interactions with CYP2B6 residues. These results show that CYP2B6 and CYP2B6-catalyzed methadone metabolism are inhibited by certain natural products, at concentrations which may be clinically relevant. SIGNIFICANCE STATEMENT: This investigation identified several natural product constituents which inhibit in vitro human recombinant CYP2B6 and CYP2B6-catalyzed N-demethylation of the opioid methadone. The most potent inhibitors (K i) were dihydromethysticin (0.074 µM), gambogic acid (6 µM) and 2,2'-dihydroxychalcone (16 µM). Molecular modeling of ligand interactions with CYP2B6 found that dihydromethysticin and 2,2'-dihydroxychalcone bound at the active site, while gambogic acid interacted with an allosteric site on the CYP2B6 surface. Natural product constituents may inhibit CYP2B6 and methadone metabolism at clinically relevant concentrations.

Low temperature compensates for defective tapetum initiation to restore the fertility of the novel TGMS line ostms15.

In rice breeding, thermosensitive genic male sterility (TGMS) lines based on the tms5 locus have been extensively employed. Here, we reported a novel rice TGMS line ostms15 (Oryza sativa ssp. japonica ZH11) which show male sterility under high temperature and fertility under low temperature. Field evaluation from 2018 to 2021 revealed that its sterility under high temperature is more stable than that of tms5 (ZH11), even with occasional low temperature periods, indicating its considerable value for rice breeding. OsTMS15 encodes an LRR-RLK protein MULTIPLE SPOROCYTE1 (MSP1) which was reported to interact with its ligand to initiate tapetum development for pollen formation. In ostms15, a point mutation from GTA (Val) to GAA (Glu) in its TIR motif of the LRR region led to the TGMS phenotype. Cellular observation and gene expression analysis showed that the tapetum is still present in ostms15, while its function was substantially impaired under high temperature. However, its tapetum function was restored under low temperature. The interaction between mOsTMS15 and its ligand was reduced while this interaction was partially restored under low temperature. Slow development was reported to be a general mechanism of P/TGMS fertility restoration. We propose that the recovered protein interaction together with slow development under low temperature compensates for the defective tapetum initiation, which further restores ostms15 fertility. We used base editing to create a number of TGMS lines with different base substitutions based on the OsTMS15 locus. This work may also facilitate the mechanistic investigation and breeding of other crops.

Statistical characteristics of under-ice noise on the Arctic Chukchi Plateau.

In the context of global warming leading to rapidly changing Arctic sea ice and the environment, it is necessary to understand the statistical characteristics of noise under existing Arctic ocean environmental conditions. The data recorded from August 1, 2018 to November 2, 2019, on the Arctic Chukchi Plateau, have been studied to analyze the relationship between the ice transient events and the non-Gaussian statistics of under-ice noise. The ice-generated transient noise largely contributes to the under-ice noise environment, and the total under-ice noise exhibits non-Gaussian statistics due to the occurrence of these ice transients. The number of ice transients has a strong negative correlation with the characteristic index α, meaning that the higher the occurrence of transient events, the stronger the non-Gaussian statistics of under-ice noise. Stronger non-Gaussian noise with full ice coverage is observed compared to partial ice coverage. The under-ice noise in 0.5-1 kHz exhibits the strongest non-Gaussian statistics, followed by 1-4 kHz, while it is weakest in 20-500 Hz. The statistics of ice transients and under-ice noise have been provided in this paper, which can be used in sonar detection algorithms and have important significance for the performance prediction and optimization of sonar processors.

Catellatospora tritici sp. nov., a novel cellulase-producing actinobacterium isolated from rhizosphere soil of wheat (Triticum aestivum L.) and emended description of the genus Catellatospora.

A Gram-positive, cellulose-degrading actinobacterium, designed strain NEAU-YM18T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) sampled in Langfang, Hebei Province, PR China. The novel strain was characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed that strain NEAU-YM18T belonged to the genus Catellatospora. Cells of strain NEAU-YM18T were observed to contain meso- and 3-hydroxy-diaminopimelic acids as diagnostic cell-wall amino acids. The acyl type of the cell-wall muramic acid was glycolyl. The whole-cell hydrolysates were xylose, glucose and ribose. The phospholipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were iso-C15 : 0, iso-C16 : 0, C18 : 1 ω9c and summed feature 5 (anteiso-C18 : 0/C18 : 2 ω6,9c). The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The DNA G+C content was 71.1 %. The results of 16S rRNA gene sequence and phylogenetic analyses indicated that strain NEAU-YM18T was closely related to Catellatospora chokoriensis 2-25(1)T (98.4 % 16S rRNA gene sequence similarity), Catellatospora vulcania NEAU-JM1T (98.3%) and Catellatospora sichuanensis H14505T (98.3 %) and formed a branch with C. sichuanensis H14505T. Furthermore, the whole genome phylogeny of strain NEAU-YM18T showed that the strain formed an independent clade. The digital DNA-DNA hybridization results between NEAU-YM18T and C. chokoriensis 2-25(1)T, C. vulcania NEAU-JM1T and C. sichuanensis H14505T were 25.0, 24.7 and 24.7 %, respectively, and the whole-genome average nucleotide identity values between them were 81.5, 81.4 and 81.4 %, respectively. These genetic results and some phenotypic characteristics could distinguish strain NEAU-YM18T from its reference strains. In addition, genomic analysis confirmed that strain NEAU-YM18T had the potential to decompose cellulose and produce bioactive compounds. Therefore, strain NEAU-YM18T represents a novel species of the genus Catellatospora, for which the name Catellatospora tritici sp. nov. is proposed. The type strain is NEAU-YM18T (=CCTCC AA 2020040T=JCM 33977T).

Nonomuraea aurantiaca sp. nov., a novel cellulase-producing actinobacterium isolated from soil.

A novel cellulase-producing actinobacterium, designated strain NEAU-L178T, was isolated from soil sample collected from Qiqihaer, Heilongjiang Province, PR China. A polyphasic study was carried out to determine the taxonomic status of the strain. On the basis of 16S rRNA gene sequence analysis, strain NEAU-L178T should be classified into the genus Nonomuraea and is closely related to Nonomuraea cavernae SYSU K10005T (99.31 % 16S rRNA gene sequence similarity), Nonomuraea glycinis NEAU-BB2C19T (98.75 %), Nonomuraea guangzhouensis NEAU-ZJ3T (98.75 %) and 'Nonomuraea rhizosphaerae' NEAU-mq18T (98.34 %). The digital DNA-DNA hybridization values between them are 27.1, 26.1, 42.0 and 30.9 %, and the whole-genome average nucleotide identity values between them are 83.1, 82.3, 90.3 and 85.8 %, respectively. The whole-cell hydrolysates contained glucose, ribose, arabinose and madurose. The menaquinones were identified as MK-9(H0), MK-9(H4) and MK-9(H2). The major fatty acids were C16 : 0, iso-C17 : 0 and C17 : 0 10-methyl. The detected polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol and three unidentified phospholipids. The genomic DNA G+C content was 69.7 mol%. In addition, whole-genome analysis indicated that strain NEAU-L178T had the potential to degrade cellulose. Based on the phenotypic, genotypic, chemotaxonomic and phylogenetic data, strain NEAU-L178T can be differentiated from its close phylogenetic relatives and represents a novel species of the genus Nonomuraea, for which the name Nonomuraea aurantiaca sp. nov. is proposed. The type strain is NEAU-L178T (=JCM 34799T=CGMCC 4.7741T).

Inhibiting endoplasmic reticulum stress mediated-autophagy enhances the pro-apoptotic effects of resveratrol derivative in colon cancer cells.

Previous studies have demonstrated that endoplasmic reticulum stress (ERS) might play a major role in inducing cellular autophagy and apoptosis in multiple types of cancer. Herein, we observed that trans-3,5,4'-trimethoxystilbene (TMS) exposure facilitated apoptotic cell death and ERS-mediated autophagy in colon cancer SW480 and HCT116 cells. Interestingly, our data demonstrated that ERS was not involved in TMS-induced apoptosis. However, ERS notably induced protective autophagy in SW480 and HCT116 cells. In addition, inhibiting cellular ERS significantly improved the pro-apoptotic effects of TMS. Thus, our results indicated that TMS-mediated autophagy was dependent on ERS, while apoptotic cell death might be induced in the ERS-independent pathway after TMS treatment. Generally, inhibiting ERS-mediated autophagy can enhance the pro-apoptotic effects of TMS. TMS might be a potential therapeutic agent for colon cancer treatment.

Glycomyces albidus sp. nov., a novel actinobacterium isolated from rhizosphere soil of wheat (Triticum aestivum L.).

A novel actinobacterium, designated strain NEAU-7082T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) and characterized by using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed the affiliation of strain NEAU-7082T to the genus Glycomyces. 16S rRNA gene sequence analysis indicated that strain NEAU-7082T belonged to the genus Glycomyces and was closely related to Glycomyces mayteni JCM 16217T (99.0 % 16S rRNA gene sequence similarity), Glycomyces sambucus DSM 45047T (98.4 %), Glycomyces scopariae DSM 44968T (98.3 %), Glycomyces paridis DSM 102295T (98.1 %), Glycomyces artemisiae NBRC 109773T (98.0 %) and Glycomyces dulcitolivorans DSM 105121T (97.9 %). Phylogenetic analysis using the 16S rRNA gene sequence showed that the strain formed a stable clade with G. mayteni JCM 16217T and clustered with G. sambucus DSM 45047T, G. scopariae DSM 44968T, G. artemisiae NBRC 109773T and G. dulcitolivorans DSM 105121T in the genus Glycomyces. The cell wall contained meso-diaminopimelic acid and the whole-cell hydrolysates were glucose and xylose. The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), glycolipid (GL), phosphatidylinositol mannoside (PIM) and an unidentified lipid (UL). The menaquinones were MK-11(H4), MK-11 and MK-10. Major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. These chemotaxonomic data substantiated the affiliation of strain NEAU-7082T to the genus Glycomyces. The DNA G+C content was 71.3 mol%. A combination of DNA-DNA hybridization results and some phenotypic characteristics demonstrated that strain NEAU-7082T could be distinguished from its closest relatives. Therefore, strain NEAU-7082T is considered to represent a novel species of the genus Glycomyces, for which the name Glycomyces albidus sp. nov. is proposed. The type strain is NEAU-7082T (=CCTCC AA 2019045T=JCM 33458T).

Fluorescence signal amplification assay for the detection of B. melitensis 16M, based on peptide-mediated magnetic separation technology and a AuNP-mediated bio-barcode assembled by quantum dot technology.

Members of the Brucella spp. are facultative intracellular bacteria that can cause global brucellosis, a zoonotic disease. Herein, a novel fluorescence signal amplification (FSA) method for the rapid detection of B. melitensis 16M was developed based on peptide-mediated magnetic separation (PMS) technology and Au nanoparticle (AuNP)-mediated bio-barcode assay technology assembled by quantum dots (QDs). The PMS technology was used to specifically capture and isolate B. melitensis 16M from food. The immunomagnetic bead-B. melitensis 16M bioconjugates (IMBs-B. melitensis 16M) were then identified by IgY on the surface of AuNPs and the oligonucleotide chains on the surface of the gold nanoparticles were hybridized with bio-barcodes assembled by quantum dots (QD-probe2). The IMB/B. melitensis 16M/IgY-AuNP-probe1/QD-probe2 bioconjugates were concentrated by magnetic separation. Therefore, as the concentration of B. melitensis 16M in the sample increased, the unbound QD-probe2 in the supernatant reduced, and the B. melitensis 16M in the sample could be indirectly measured by detecting the fluorescence in the supernatant. This FSA method can detect B. melitensis 16M concentration in the range of 10 to 106 cfu ml-1 without pre-enrichment, and the limit of detection (LOD) is as low as 10 cfu ml-1 with high specificity. Furthermore, the proposed method for the detection of B. melitensis 16M has a LOD of 1.07 × 102 cfu ml-1 and a linear range from 102 to 107 cfu ml-1 in milk, and a LOD of 1.72 × 102 cfu ml-1, and a linear range from 102 to 106 cfu ml-1 in lamb leach. In addition, this method takes less than 3 h to perform. Thus, the assay that was developed in this study shows promise for rapid, sensitive, and specific detection of B. melitensis 16M.

The Efficacy and Safety of Dendritic Cells Co-Cultured with Cytokine-Induced Killer Cell Therapy in Combination with TACE-Predominant Minimally-Invasive Treatment for Hepatocellular Carcinoma: a Meta-Analysis.

BACKGROUND: To evaluate the efficacy and safety of dendritic cells (DCs) co-cultured with cytokine-induced killer cell (CIK) immunotherapy combined with transcatheter arterial chemoembolization (TACE) or TACE plus local ablation therapy for hepatocellular carcinoma (HCC). METHODS: Our meta-analysis included a comprehensive search for relevant studies published through December 12, 2014. We used Cochrane Library, PubMed, CBM, VIP, CNKI, and Wanfang data. Depending on the heterogeneity among the included studies, we calculated the pooled odds ratio (OR) and mean difference (MD) using fixed- or random-effects models. Publication biases were assessed using funnel plots and Begg's tests. Sensitivity analyses were also performed. RESULTS: Seven randomized controlled trials (RCTs) and one controlled clinical trial (CCT) that included 693 patients and met the inclusion criteria were analyzed. Pooled results showed that DC-CIK immunotherapy combined with TACE or TACE plus local ablation therapy significantly improved 1-year (OR = 2.00, p = 0.02) and 2-year overall survival (OR = 1.77, p = 0.04). A favored overall response rate (ORR) (OR = 1.51, p = 0.03), disease control rate (DCR) (OR = 1.81, p = 0.01), and better quality of life (OR = 3.30, p < 0.01) were observed in the DC-CIK group. Additionally, when tumor-associated T lymphocyte subsets were compared, our analyses demonstrated that the percentage of CD3+ T cells (MD(CD3+) = 21.37, p = 0.005) and the ratio of CD4+/CD8+ (MD(CD4+/CD8+) = 2.83, p = 0.02) were significantly increased in the DC-CIK therapy group. CONCLUSIONS: The combination of DC-CIK immunotherapy and TACE or TACE plus local ablation therapy improves 1- and 2-year overall survival, ORR, DCR, and provides a better quality of life for patients with HCC.

Effects of human milk odor stimulation on feeding in premature infants: a systematic review and meta-analysis.

Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = - 0.48, 95% CI (- 0.69, - 0.27), Z = 4.54, P < 0.00001] and shortened the duration of parenteral nutrition [MD = - 1.01, 95% CI (- 1.70, - 0.32), Z = 2.88, P = 0.004]. However, it did not change the length of hospitalization for premature infants [MD = - 0.03, 95% CI (- 0.41, 0.35), Z = 0.17, P = 0.86]. The implementation of human milk odor stimulation can reduce the transition time to oral feeding and the duration of parenteral nutrition in premature infants, but further studies are needed to determine whether it can reduce the length of hospital stay in premature infants. More high-quality, large-sample studies are needed to investigate the effect of human milk odor stimulation on the feeding process and other outcomes in premature infants.

Earthquake supercycles and fault interaction over the past 32 ka in the Lake Ebinur area, Xinjiang, China.

Earthquake prediction and disaster assessment in tectonically active regions require a continuous and complete regional seismic archive, which is commonly difficult to obtain, especially for prehistoric records. Here, high-resolution analysis of the sedimentary sequence from Lake Ebinur in Xinjiang revealed a detailed history of environment evolution since 32 ka ago. Both the Cl content and ultrafine proportion revealed the changing climate: the climate was relatively dry with low lake-water volumes from 32 to 12 ka, while the climate became warmer and wetter since 12 ka. In addition, eight earthquakes were identified by comprehensive analysis of grain size and geochemical element proxies, showing more than two seismic supercycles, with gaps of ∼10.4 ka; these gaps are much larger than those inferred previously (∼4-7 ka). Notably, these seismic events exhibited a pattern of mutual transmittance between the BoA and Jinghenan faults. Such fault interaction can occur in the Lake Ebinur area because it is dominated by weak lithosphere in which strain is easily accumulated and released; the interaction can also be attributed to the unique spatial distribution and immature nature of both faults. Combined with trenching investigations, our high-resolution analysis of lacustrine sediments can reveal a complete history of tectonic activity, which can efficiently serve regional earthquake prediction and disaster assessment.

Spatio-temporal microbial regulation of aggregate-associated priming effects under contrasting tillage practices.

Tillage intensity significantly influences the heterogeneous distribution and dynamic changes of soil microorganisms, consequently shaping spatio-temporal patterns of SOC decomposition. However, little is known about the microbial mechanisms by which tillage intensity regulates the priming effect (PE) dynamics in heterogeneous spatial environments such as aggregates. Herein, a microcosm experiment was established by adding 13C-labeled straw residue to three distinct aggregate-size classes (i.e., mega-, macro-, and micro-aggregates) from two long-term contrasting tillage histories (no-till [NT] and conventional plow tillage [CT]) for 160 days to observe the spatio-temporal variations in PE. Metagenomic sequencing and Fourier transform mid-infrared techniques were used to assess the relative importance of C-degrading functional genes, microbial community succession, and SOC chemical composition in the aggregate-associated PE dynamics during straw decomposition. Spatially, straw addition induced a positive PE for all aggregates, with stronger PE occurring in larger aggregates, especially in CT soil compared to NT soil. Larger aggregates have more unique microbial communities enriched in genes for simple C degradation (e.g., E5.1.3.6, E2.4.1.7, pmm-pgm, and KduD in Nitrosospeera and Burkholderia), contributing to the higher short-term PE; however, CT soils harbored more genes for complex C degradation (e.g., TSTA3, fcl, pmm-pgm, and K06871 in Gammaproteobacteria and Phycicoccus), supporting a stronger long-term PE. Temporally, soil aggregates played a significant role in the early-stage PEs (i.e., < 59 days after residue addition) through co-metabolism and nitrogen (N) mining, as evidenced by the increased microbial biomass C and dissolved organic C (DOC) and reduced inorganic N with increasing aggregate-size class. At a later stage, however, the legacy effect of tillage histories controlled the PEs via microbial stoichiometry decomposition, as suggested by the higher DOC-to-inorganic N and DOC-to-available P stoichiometries in CT than NT. Our study underscores the importance of incorporating both spatial and temporal microbial dynamics for a comprehensive understanding of the mechanisms underlying SOC priming, especially in the context of long-term contrasting tillage practices.

Effect of dexmedetomidine infusion on postoperative sleep disturbances in women with breast cancer: A monocentric randomized-controlled double-blind trial.

BACKGROUND: Most women with breast cancer are prone to postoperative sleep disturbances (POSD). Little is known about the differences between sevoflurane and propofol combined with dexmedetomidine on POSD in the same context. We investigated the effect of intra-operative sevoflurane or propofol combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep structures. METHODS: A monocentric, randomized-controlled, double-blind trial. Female patients undergoing radical surgery for breast cancer were randomly assigned to receive sevoflurane and placebo, sevoflurane and dexmedetomidine, propofol and placebo, or propofol and dexmedetomidine. Dexmedetomidine was administered at 1.0 µg kg-1 infusion 15 min before induction, then infused at 0.4 µg kg-1 h-1 until the surgical drain started to be placed. The primary outcome was the incidence of POSD within the postoperative first three days (defined as an Athens Insomnia Scale score ≥ 6 points on at least one day of postoperative first three days). The secondary outcome was the duration of sleep structures, collected from the Fitbit Charge 2® smart bracelet (Fitbit, Inc., San Francisco, CA, USA). RESULTS: There were 188 women analyzed with the modified intention-to-treat method. The incidences of POSD in the dexmedetomidine and placebo groups were similar (p = 0.649). In the sevoflurane sedation strategy, dexmedetomidine decreased nocturnal wakefulness on postoperative first day (p = 0.001). In the propofol sedation strategy, dexmedetomidine increased nocturnal deep sleep on postoperative first (p < 0.001) and third (p < 0.001) days. CONCLUSION: Intra-operative infusion of dexmedetomidine had no significant effect on POSD but decreased nocturnal wakefulness in the sevoflurane group and increased nocturnal deep sleep in the propofol group. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2300070136).

Microbiota profiling reveals alteration of gut microbial neurotransmitters in a mouse model of autism-associated 16p11.2 microduplication.

The gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/ß-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.

MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target.

Women worldwide are more likely to develop breast cancer (BC) than any other type of cancer. The treatment of BC depends on the subtype and stage of the cancer, such as surgery, radiotherapy, chemotherapy, and immunotherapy. Although significant progress has been made in recent years, advanced or metastatic BC presents a poor prognosis, due to drug resistance and recurrences. During embryonic development, myeloid-derived suppressor cells (MDSCs) develop that suppress the immune system. By inhibiting anti-immune effects and promoting non-immune mechanisms such as tumor cell stemness, epithelial-mesenchymal transformation (EMT) and angiogenesis, MDSCs effectively promote tumor growth and metastasis. In various BC models, peripheral tissues, and tumor microenvironments (TME), MDSCs have been found to amplification. Clinical progression or poor prognosis are strongly associated with increased MDSCs. In this review, we describe the activation, recruitment, and differentiation of MDSCs production in BC, the involvement of MDSCs in BC progression, and the clinical characteristics of MDSCs as a potential BC therapy target.

Ocean ambient noise on the Chukchi Plateau and its environmental correlates.

Conducting research on ocean ambient noise under different sea ice conditions is highly important for the comprehension of the rapidly changing Arctic. We present the first results of ambient noise and its relationship to environmental forcing during the open-water, ice transition and ice-covered periods on the Chukchi Plateau. The ambient noise level (ANL) in the 20 Hz to 2 kHz band is higher, intermediate and lower during the open-water, ice transition and ice-covered periods, respectively. During the ice-covered period, the ambient noise is dominated by the ice-generated noise due to sea ice activities and shows a negative correlation with temperature. Therefore, when the temperature decreases, the sea ice is prone to shrinking and cracking, thus increasing the sea ice activities and resulting in increased ice-generated noise; when the temperature rises and is relatively high in May and June, the ANL is lowest for the sea ice inhibition to wind waves and decreased sea ice activities induced by temperature rise. Sea ice is the most predominant environmental factor affecting Arctic ocean ambient noise, and the ANL can potentially increase due to a reduction in Arctic sea ice and increase in human activities caused by global climate change.

Behavioral responses of two captive bottlenose dolphins (Tursiops truncatus) to a continuous 50 kHz tone.

At present, the fundamental frequencies of signals of most commercially available acoustic alarms to deter small cetaceans are below 20 kHz, but it is not well ascertained whether higher frequencies have a deterrent effect on bottlenose dolphins (Tursiops truncatus). Two captive bottlenose dolphins housed in a floating pen were subjected to a continuous pure tone at 50 kHz with a source level of 160 ± 2 dB (re 1 µPa, rms). The behavioral responses of dolphins were judged by comparing surfacing distance relative to the sound source, number of surfacings, and number of echolocation clicks produced, during forty 15 min baseline periods with forty 15 min test periods (four sessions per day, 40 sessions in total). On all 10 study days, surfacing distance and the number of surfacings increased while click production decreased during broadcasts of test sound. The avoidance threshold sound pressure level for a continuous 50 kHz tone for the bottlenose dolphins, in the context of this study, was estimated to be 144 ± 2 dB (re 1 µPa, rms). The results indicated that a continuous 50 kHz tonal signal can deter bottlenose dolphins from an area.

A Novel LOC101927967 Intergenic Region ALK Fusion Identified by NGS and Validated by IHC and FISH in a Patient with Early Stage Adenocarcinoma of Lung.

Anaplastic lymphoma kinase (ALK) gene rearrangement is an essential driver mutation identified in approximately 5% of non-small cell lung cancers (NSCLCs). The results of clinical trials have demonstrated the impressive efficacy of ALK tyrosine kinase inhibitors (ALK-TKIs). Besides the classic EML4-ALK fusions, a growing list of gene fusion partners for ALK in NSCLC have been identified with heterogeneous clinical responses to ALK-TKIs. However, a LOC101927967-ALK fusion has not been reported in NSCLC. Herein, a novel LOC101927967 downstream intergenic region ALK fusion in an early-stage patient with lung adenocarcinoma was first identified by next-generation sequencing (NGS) and verified by immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH), which might provide a treatment option for postoperative recurrence.