Dormant bacterial spores encrypt a long-lasting transcriptional program to be executed during revival.

Sporulating bacteria can retreat into long-lasting dormant spores that preserve the capacity to germinate when propitious. However, how the revival transcriptional program is memorized for years remains elusive. We revealed that in dormant spores, core RNA polymerase (RNAP) resides in a central chromosomal domain, where it remains bound to a subset of intergenic promoter regions. These regions regulate genes encoding for most essential cellular functions, such as rRNAs and tRNAs. Upon awakening, RNAP recruits key transcriptional components, including sigma factor, and progresses to express the adjacent downstream genes. Mutants devoid of spore DNA-compacting proteins exhibit scattered RNAP localization and subsequently disordered firing of gene expression during germination. Accordingly, we propose that the spore chromosome is structured to preserve the transcriptional program by halting RNAP, prepared to execute transcription at the auspicious time. Such a mechanism may sustain long-term transcriptional programs in diverse organisms displaying a quiescent life form.

Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.

Tripterygium glycosides reverse chemotherapy resistance in ovarian cancer by targeting the NRF2/GPX4 signal axis to induce ferroptosis of drug-resistant human epithelial ovarian cancer cells.

Cisplatin resistance is the main cause of postoperative recurrence and difficulty in the treatment of ovarian cancer. It is urgently needed to identify therapeutic drugs with unique functions to overcome the current challenges in the treatment of ovarian cancer. In this study, we found that TG promoted the accumulation of ROS and MDA in A2780/DDP cells and downregulated the expression of key antioxidant molecules. In vivo, the survival rate of tumor-bearing nude mice was prolonged by TG without significant hepatotoxic reaction. The expression of key antioxidant molecules in tumor tissues was consistent with that in vitro. These findings revealed that TG disrupted homeostasis of redox reactions and induced ferroptosis in A2780/DDP cells, thereby enhancing cisplatin chemosensitivity of ovarian cancer. Overall, TG may be a novel potential therapeutic option for reversing resistance to cisplatin chemotherapy.

Eu3+-Doped (Gd, La)AlO3 Perovskite Single Crystals: Growth and Red-Emitting Luminescence.

Eu3+-doped GdAlO3 (Eu:GAP) and Gd0.5La0.5AlO3 (Eu:GLAP) perovskite single crystals were successfully grown using the optical floating zone (OFZ) method. The microstructure, optical, photoluminescence (PL) and radioluminescence (under X-ray excitation, XEL) were investigated. Under the PL excitation of 275 nm, obvious emission bands peaking at 556 nm, 592 nm, 617 nm, 625 nm, 655 nm, and 706 nm were demonstrated, which correspond to the 5D0 → 7Fj (j = 0-4) transitions of Eu3+. The grown Eu:GAP single crystal showed a stronger PL intensity compared with that of Eu:GLAP in the red light region. After annealing at 1000 °C for 4 h in weak reductive atmosphere (Ar + 5% H2), a slight redshift and dramatic enhancement of PL and XEL intensity occurred. In addition, Eu:GLAP show a more intense XEL emission than that of Eu:GAP. Considering their different densities, these two kinds of red luminescence phosphors are proposed to be promising in a wide field of X-ray imaging, warm white, or plant lighting, respectively.

Ce3+, Pr3+ Co-Doped Lu3Al5O12 Single Crystals and Ceramics: A Comparative Study.

Ce3+, Pr3+ co-doped Lu3Al5O12 (Ce, Pr:LuAG) single crystals and ceramics were prepared using the optical floating zone (OFZ) and reactive vacuum sintering methods, respectively. The microstructure, photo- (λex = 450 nm), and radio-luminescence (under X-ray excitation) performance, as well as scintillation light yield (LY, under γ-ray, 137Cs source) of both materials, were investigated and compared. Ce, Pr:LuAG ceramics had an in-line transmittance of approximately 20% in the visible light range, while the analogous crystals were more transparent (~65%). The X-ray excited luminescent (XEL) spectra showed the characteristic Ce 3+ and Pr3+ emissions located at 310 nm, 380 nm, and 510 nm. The highest LY of the Ce, Pr:LuAG ceramics reached 34,112 pho/MeV at 2 µs time gate, which is higher than that of a single crystal. The ratio of LY values (LY2/LY0.75) between shaping times of 0.75 µs and 2 µs indicated a faster scintillation decay of ceramics regarding single crystals. It was ascribed to the lower effective concentration of luminescent activators in single crystals because of the coefficient segregation effect.

Colossal Nernst power factor in topological semimetal NbSb2.

Today solid-state cooling technologies below liquid nitrogen boiling temperature (77 K), crucial to quantum information technology and probing quantum state of matter, are greatly limited due to the lack of good thermoelectric and/or thermomagnetic materials. Here, we report the discovery of colossal Nernst power factor of 3800 × 10-4 W m-1 K-2 under 5 T at 25 K and high Nernst figure-of-merit of 71 × 10-4 K-1 under 5 T at 20 K in topological semimetal NbSb2 single crystals. The observed high thermomagnetic performance is attributed to large Nernst thermopower and longitudinal electrical conductivity, and relatively low transverse thermal conductivity. The large and unsaturated Nernst thermopower is the result of the combination of highly desirable electronic structures of NbSb2 having compensated high mobility electrons and holes near Fermi level and strong phonon-drag effect. This discovery opens an avenue for exploring material option for the solid-state heat pumping below liquid nitrogen temperature.

Antibiotic Therapy and Vaginal Microbiota Transplantation Reduce Endometriosis Disease Progression in Female Mice via NF-κB Signaling Pathway.

Endometriosis (EMS) is a disease characterized by estrogen-dependent, chronic inflammatory, and annoying symptoms, which inflicts about 10% reproductive-age women. The diagnosis of endometriosis mainly depends on pathological examination after surgical resection while the pathogenesis of EMS is not clear enough. Surgical resection and drug therapy (including painkillers and hormone therapy, especially gonadotropin-releasing hormone analogs, GnRH-a) are widely used, but they are expensive and have many side effects. There are few studies on vaginal microorganisms in women with endometriosis. We collected vaginal secretions from women with EMS confirmed by pathology and demonstrated that they were different from that of healthy women by 16s rRNA high-throughput sequencing. Additionally, we established the EMS model in female mice by intraperitoneally injecting fragments from donor mice (3-week growth). Then, the mice were treated with mixed antibiotics (vagina) and NF-κB signaling pathway inhibitors (intraperitoneal injection), respectively. The result suggested that the ectopic lesions were inhibited. In addition, inflammatory cytokines IL-1ß, IL-6, and TNF-α in peritoneal fluid, cell proliferation marker ki-67, and macrophage marker Iba-1 in ectopic lesions decreased significantly from that of mock mice. We also observed similar results as above by vaginal microbiota transplantation (VMT) and subcutaneous injection of leuprorelin acetate (LA, one of GnRH-a) for mice with EMS. These results showed that vaginal use of antibiotics or VMT is helpful to treat endometriosis in mice. However, due to the great difference between human and mouse vaginal microbiota, its mechanism and clinical transformation application still need to be further studied in the future.

High-Throughput Screening for Thermoelectric Semiconductors with Desired Conduction Types by Energy Positions of Band Edges.

The conduction type of semiconductors is vitally important in many fields (e.g., photovoltaics, transistors, and thermoelectrics), but so far, there is no effective and simple indicator to quickly judge or predict the conduction type of various semiconductors. In this work, based on the relationship between the formation energy of charged defect and the Fermi level, we propose a simple and low-cost strategy for high-throughput screening the potential n-type or p-type semiconductors from the material database by using energy positions of band edges as indicators. As a case study, we validate this strategy in searching potential n-type thermoelectric materials from copper (Cu)-containing metal chalcogenides. A new promising thermoelectric material, CuIn5Se8, with potential intrinsic n-type conduction, is successfully screened from 407 Cu-containing metal chalcogenides and validated in the subsequent experiments. Upon doping iodine in CuIn5Se8, a peak thermoelectric figure of merit zT of 0.84 is obtained at 850 K. Beyond thermoelectrics, the strategy proposed in this study also sheds light on the new material development with desired conduction types in photovoltaics, transistors, and other fields.

Wide Concentration Range of Tb3+ Doping Influence on Scintillation Properties of (Ce, Tb, Gd)3Ga2Al3O12 Crystals Grown by the Optical Floating Zone Method.

To obtain a deeper understand of the energy transfer mechanism between Ce3+ and Tb3+ ions in the aluminum garnet hosts, (Ce, Tb, Gd)3Ga2Al3O12 (GGAG:Ce, Tb) single crystals grown by the optical floating zone (OFZ) method were investigated systematically in a wide range of Tb3+ doping concentration (1-66 at.%). Among those, crystal with 7 at.% Tb reached a single garnet phase while the crystals with other Tb3+ concentrations are mixed phases of garnet and perovskite. Obvious Ce and Ga loss can be observed by an energy dispersive X-ray spectroscope (EDS) technology. The absorption bands belonging to both Ce3+ and Tb3+ ions can be observed in all crystals. Photoluminescence (PL) spectra show the presence of an efficient energy transfer from the Tb3+ to Ce3+ and the gradually quenching effect with increasing of Tb3+ concentration. GGAG: 1% Ce3+, 7% Tb3+ crystal was found to possess the highest PL intensity under excitation of 450 nm. The maximum light yield (LY) reaches 18,941 pho/MeV. The improved luminescent and scintillation characteristics indicate that the cation engineering of Tb3+ can optimize the photoconversion performance of GGAG:Ce.

Revealing the Disturbed Vaginal Micobiota Caused by Cervical Cancer Using High-Throughput Sequencing Technology.

Cervical cancer is the fourth most prevalent cancer type among all malignancies, so it is of great significance to find its actual pathogenesis mechanisms. In the present study, 90 women were enrolled, and high-throughput sequencing technology was firstly used to analyze the vaginal microbiota of healthy women (C group), cervical intraepithelial neoplasia patients (CIN group) and cervical cancer patients (CER group). Our results indicates that compared with C group, a higher HPV infection rate as well as increased Neutrophil ratio and tumor marker squamous cell carcinoma antigen (SCCA) were obtained, and a decrease in Lymphocyte ratio and Hemoglobin were also present. In addition, the cervical cancer showed a strong association with reduced probiotics Lactobacillus, increased pathogens Prevotella spp., Sneathia spp. and Pseudomonas spp. These results prove that the immunological changes generated by the cervical cancer and the vaginal microbiota can interact with each other. However, further study investigating the key bacteria for cervical cancer is still needed, which can be a clue for the diagnosis or treatment of cervical cancer.

Ternary Compounds Cu3RTe3 (R = Y, Sm, and Dy): A Family of New Thermoelectric Materials with Trigonal Structures.

In this work, we report a series of Cu3RTe3 (R = Y, Sm, and Dy) ternary compounds with a trigonal structure (R3̅) as a family of new thermoelectric materials. First-principles calculations show that Cu3RTe3 (R = Y, Sm, and Dy) compounds are semiconductors with similar band structures and moderate band gaps (0.69-0.82 eV). The synthesized polycrystalline Cu3RTe3 (R = Y, Sm, and Dy) compounds possess moderate carrier concentrations (0.8-2.2 × 1020 cm-3) and density-of-state effective masses (around 1.1 me), yielding decent electrical transport performance. Furthermore, intrinsically low lattice thermal conductivities, below 1 W m-1 K-1 at 300-900 K, originating from the heavy average atomic masses and large number of atoms in the unit cell, are observed for Cu3RTe3 (R = Y, Sm, and Dy). Finally, Cu3DyTe3 demonstrates a peak dimensionless figure of merit of 0.9 at 900 K, which is among the highest reported for the Cu/Ag-based tellurides.

Characterization of Five Escherichia coli Isolates Co-expressing ESBL and MCR-1 Resistance Mechanisms From Different Origins in China.

Present study characterized five Escherichia coli co-expressing ESBL and MCR-1 recovered from food, food-producing animals, and companion animals in China. Antimicrobial susceptibility tests, conjugation experiments, and plasmid typing were performed. Whole genome sequencing (WGS) was undertaken for all five isolates using either PacBio RS II or Illumina HiSeq 2500 platforms. The cefotaxime and colistin resistance encoded by bla CTX-M and mcr-1 genes, respectively, was transferable by conjugation either together or separately for all five strains. Interestingly, the ESBL and mcr-1 genes could be co-selected by cefotaxime, while the colistin only selected the mcr-1-carrying plasmids during the conjugation experiments. Five E. coli sequence types (ST88, ST93, ST602, ST162, and ST457) were detected. Although diverse plasmid profiles were identified, IncI2, IncFIB, and IncFII plasmid types were predominant. These five clonally unrelated isolates harbored the mcr-1 gene located on similar plasmid backbones, which showed high nucleotide similarity to plasmid pHNSHP45. The mcr-1 gene can be co-transmitted with bla CTX-M genes through IncI2 plasmids with or without ISApl1 in our study. Characterization of these co-existence ESBL and mcr-1 isolates extends our understanding on the dissemination of these resistance markers among bacteria of diverse origins.