Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Effects of aneuploidy on cell behaviour and function.

Aneuploidy, a genomic alternation characterized by deviations in the copy number of chromosomes, affects organisms from early development through to aging. Although it is a main cause of human pregnancy loss and a hallmark of cancer, how aneuploidy affects cellular function has been elusive. The last two decades have seen rapid advances in the understanding of the causes and consequences of aneuploidy at the molecular and cellular levels. These studies have uncovered effects of aneuploidy that can be beneficial or detrimental to cells and organisms in an environmental context-dependent and karyotype-dependent manner. Aneuploidy also imposes general stress on cells that stems from an imbalanced genome and, consequently, also an imbalanced proteome. These insights provide the fundamental framework for understanding the impact of aneuploidy in genome evolution, human pathogenesis and drug resistance.

Crystal-Phase Engineering in Heterogeneous Catalysis.

The performance of a chemical reaction is critically dependent on the electronic and/or geometric structures of a material in heterogeneous catalysis. Over the past century, the Sabatier principle has already provided a conceptual framework for optimal catalyst design by adjusting the electronic structure of the catalytic material via a change in composition. Beyond composition, it is essential to recognize that the geometric atomic structures of a catalyst, encompassing terraces, edges, steps, kinks, and corners, have a substantial impact on the activity and selectivity of a chemical reaction. Crystal-phase engineering has the capacity to bring about substantial alterations in the electronic and geometric configurations of a catalyst, enabling control over coordination numbers, morphological features, and the arrangement of surface atoms. Modulating the crystallographic phase is therefore an important strategy for improving the stability, activity, and selectivity of catalytic materials. Nonetheless, a complete understanding of how the performance depends on the crystal phase of a catalyst remains elusive, primarily due to the absence of a molecular-level view of active sites across various crystal phases. In this review, we primarily focus on assessing the dependence of catalytic performance on crystal phases to elucidate the challenges and complexities inherent in heterogeneous catalysis, ultimately aiming for improved catalyst design.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Genome architecture and stability in the Saccharomyces cerevisiae knockout collection.

Despite major progress in defining the functional roles of genes, a complete understanding of their influences is far from being realized, even in relatively simple organisms. A major milestone in this direction arose via the completion of the yeast Saccharomyces cerevisiae gene-knockout collection (YKOC), which has enabled high-throughput reverse genetics, phenotypic screenings and analyses of synthetic-genetic interactions1-3. Ensuing experimental work has also highlighted some inconsistencies and mistakes in the YKOC, or genome instability events that rebalance the effects of specific knockouts4-6, but a complete overview of these is lacking. The identification and analysis of genes that are required for maintaining genomic stability have traditionally relied on reporter assays and on the study of deletions of individual genes, but whole-genome-sequencing technologies now enable-in principle-the direct observation of genome instability globally and at scale. To exploit this opportunity, we sequenced the whole genomes of nearly all of the 4,732 strains comprising the homozygous diploid YKOC. Here, by extracting information on copy-number variation of tandem and interspersed repetitive DNA elements, we describe-for almost every single non-essential gene-the genomic alterations that are induced by its loss. Analysis of this dataset reveals genes that affect the maintenance of various genomic elements, highlights cross-talks between nuclear and mitochondrial genome stability, and shows how strains have genetically adapted to life in the absence of individual non-essential genes.

Knoevenagel C═C Metathesis Enabled Glassy Vitrimers with High Rigidity, Toughness, and Malleability.

Thermosets, characterized by their permanent cross-linked networks, present significant challenges in recyclability and brittleness. In this work, we explore a polarized Knoevenagel C═C metathesis reaction for the development of rigid yet tough and malleable thermosets. Initial investigation on small molecule model reactions reveals the feasibility of conducting the base-catalyzed C═C metathesis reaction in a solvent-free environment. Subsequently, thermosetting poly(α-cyanocinnamate)s (PCCs) were synthesized via Knoevenagel condensation between a triarm cyanoacetate star and a dialdehyde. The thermal and mechanical properties of the developed PCCs can be easily modulated by altering the structure of the dialdehyde. Remarkably, the introduction of ether groups into the PCC leads to a combination of high rigidity and toughness with Young's modulus of ∼1590 MPa, an elongation at break of ∼79%, and a toughness reaching ∼30 MJ m3. These values are competitive to traditional thermosets, in Young's modulus but far exceed them in ductility and toughness. Moreover, the C═C metathesis facilitates stress relaxation within the bulk polymer networks, thus rendering PCCs excellent malleability and reprocessability. This work overcomes the traditional limitations of thermosets, introducing groundbreaking insights for the design of rigid yet tough and malleable thermosets, and contributing significantly to the sustainability of materials.

Recyclable, Malleable, and Strong Thermosets Enabled by Knoevenagel Adducts.

Plastic recycling is critical for waste management and achieving a circular economy, but it entails difficult trade-offs between performance and recyclability. Here, we report a thermoset, poly(α-cyanocinnamate) (PCC), synthesized using Knoevenagel condensation between terephthalaldehyde (TPA) and a triarm cyanoacetate star, that tackles this difficulty by harnessing its intrinsically conjugated and dynamic chemical characteristics. PCCs exhibit extraordinary thermal and mechanical properties with a typical Tg of ∼178 °C, Young's modulus of 3.8 GPa, and tensile strength of 102 MPa, along with remarkable flexibility and dimensional and chemical stabilities. Furthermore, end-of-life PCCs can be selectively degraded and partially recycled back into one starting monomer TPA for a new production cycle or reprocessed through dynamic exchange aided by cyanoacetate chain-ends. This study lays the scientific groundwork for the design of robust and recyclable thermosets, with transformative potential in plastic engineering.

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

Clinical application of serum tumor abnormal protein in prostate cancer patients.

PURPOSE: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. METHODS: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. RESULTS: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. CONCLUSION: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Molecular Insights into the Effect of Cholesterol on the Binding of Bicarbonate Ions in Band 3 Protein.

Band 3, or anion exchanger 1 (AE1), is one of the indispensable transmembrane proteins involved in the effective respiratory process of the human body and is primarily responsible for the exchange of bicarbonate and chloride anions across the plasma membrane of erythrocyte. However, the molecular mechanism of ion transport of Band 3 is not completely understood, yet. In this work, we systematically investigate the key binding sites of bicarbonate ions in Band 3 and the impact of cholesterol (CHOL) in lipid bilayers on bicarbonate ion binding using all-atom molecular dynamics (MD) simulations. We examine the dynamics of interactions of bicarbonate ions with Band 3 in the microsecond time scale and calculate the binding free energy of the anion in Band 3. The results indicate that the residue R730 of Band 3 is the most probable binding site for bicarbonate ions. CHOL enhances the bicarbonate ion binding by influencing the conformational stability of Band 3 and compressing the volume of the Band 3 cavity. These findings provide some insights into the bicarbonate ion binding in Band 3 and are helpful for understanding the anion exchange of Band 3.

Tripartite-motif 3 represses ovarian cancer progression by downregulating lactate dehydrogenase A and inhibiting AKT signaling.

The E3 ubiquitin ligase Tripartite-motif 3 (TRIM3) is known to play a crucial role in tumor suppression in various tumors through different mechanisms. However, its function and mechanism in ovarian cancer have yet to be elucidated. Our study aims to investigate the expression of TRIM3 in ovarian cancer and evaluate its role in the development of the disease. Our findings revealed a significant decrease in TRIM3 mRNA and protein levels in ovarian cancer tissues and cells when compared to normal ovarian epithelial tissues and cells. Furthermore, we observed a negative correlation between the protein level of TRIM3 and the FIGO stage, as well as a positive correlation with the survival of ovarian cancer patients. Using gain and loss of function experiments, we demonstrated that TRIM3 can inhibit cell proliferation, migration and invasion of the ovarian cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistic studies showed that TRIM3 interacts with lactate dehydrogenase A, a key enzyme in the glycolytic pathway, through its B-box and coiled-coil domains and induces its ubiquitination and proteasomal degradation, leading to the inhibition of glycolytic ability in ovarian cancer cells. RNA-sequencing analysis revealed significant alterations in the phosphatidylinositol signaling pathways upon TRIM3 overexpression. Additionally, overexpression of TRIM3 inhibited the phosphorylation of AKT. In conclusion, our study demonstrated that TRIM3 exerts a tumor-suppressive effect in ovarian cancer, at least partially, by downregulating LDHA and inhibiting the AKT signaling pathway, and thus leading to the inhibition of glycolysis and limiting the growth of ovarian cancer cells.

Synthesis of Biobased Poly(butylene Furandicarboxylate) Containing Polysulfone with Excellent Thermal Resistance Properties.

A synthetic biopolymer derived from furandicarboxylic acid monomer and hydroxyethyl-terminated poly(ether sulfone) is presented. The synthesis involves 4,4'-dichlorodiphenyl sulfone and 4,4-dihydroxydiphenyl sulfone, resulting in poly(butylene furandicarboxylate)-poly(ether sulfone) copolyesters (PBFES) through melt polycondensation with titanium-catalyzed polymerization. This facile method yields segmented polyesters incorporating polysulfone, creating a versatile group of high-temperature thermoplastics with adjustable thermomechanical properties. The PBFES copolyesters demonstrate an impressive tensile modulus of 2830 MPa and a tensile strength of 84 MPa for PBFES55. Additionally, the poly(ether sulfone) unit imparts a relatively high glass transition temperature (Tg), ranging from 36.6 °C for poly(butylene 2,5-furandicarboxylate) to 112.3 °C for PBFES62. Moreover, the complete amorphous film of PBFES exhibits excellent transparency and solvent resistance, making it suitable for applications, such as food packaging materials.

CircUGGT2 downregulation by METTL14-dependent m6A modification suppresses gastric cancer progression and cisplatin resistance through interaction with miR-186-3p/MAP3K9 axis.

Chemoresistance is a major therapeutic challenge in advanced gastric cancer (GC). N6-methyladenosine (m6A) RNA modification has been shown to play fundamental roles in cancer progression. However, the underlying mechanisms by which m6A modification of circRNAs contributes to GC and chemoresistance remain unknown. We found that hsa_circ_0030632 (circUGGT2) was a predominant m6A target of METTL14, and METTL14 knockdown (KD) reduced circUGGT2 m6A levels but increased its mRNA levels. The expression of circUGGT2 was markedly increased in cisplatin (DDP)-resistant GC cells. CircUGGT2 KD impaired cell growth, metastasis and DDP-resistance in vitro and in vivo, but circUGGT2 overexpression prompted these effects. Furthermore, circUGGT2 was validated to sponge miR-186-3p and upregulate MAP3K9 and could abolish METTL14-caused miR-186-3p upregulation and MAP3K9 downregulation in GC cells. circUGGT2 negatively correlated with miR-186-3p expression and harbored a poor prognosis in patients with GC. Our findings unveil that METTL14-dependent m6A modification of circUGGT2 inhibits GC progression and DDP resistance by regulating miR-186-3p/MAP3K9 axis.

Biological characteristics and pathogenicity of a Staphylococcus aureus strain with an incomplete hemolytic phenotype isolated from bovine milk.

Staphylococcus aureus is a common pathogen capable of infecting both humans and animals and causing various severe diseases. Here, we aimed to determine the biological features and pathogenicity of S. aureus strain Sa9, of the incomplete hemolysis phenotype, isolated from bovine milk. Sa9 was classified as ST97 by multilocus sequence typing, and it showed increased ß-hemolysin expression and lower Hla and Hld expression levels compared with that in the S. aureus USA300 strain LAC. RT-PCR and ELISA results showed that the expression levels of inflammatory cytokines were higher in Sa9-induced mouse primary peritoneal macrophages compared with those induced by the LAC strain. However, the Sa9 strain also mediated anti-inflammatory effects by upregulating IL-10 and IFN-ß in macrophages, which were not apparently induced by S. aureus culture supernatants. Phagocytosis and whole-blood survival assays were also performed to assess the in vitro survival of bacteria, and the virulence was evaluated in mice. Although the Sa9 strain showed lower ability of intracellular survival in macrophages than LAC, similar multiplication in human whole blood and pathogenicity toward mice were observed. Taken together, we report that the distinctive immune response induced by the S. aureus strain with an incomplete hemolysis phenotype occurs in cattle, and its potential pathogenicity and risk of transmission to humans require attention.

The prevention effect of Limosilactobacillus reuteri on acute kidney injury by regulating gut microbiota.

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.

Computer-aided designing of a novel multi­epitope DNA vaccine against severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins--nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.

Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.