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Abstract IS630/Tc1/mariner (ITm) represents the most widely distributed superfamily of DNA transposons in nature. Currently, bioinformatics research on ITm members primarily involves collecting data of existing and emerging members and organizing them into new groups or families. In the present study, our survey revealed that Tc1 and IS630 members have a broad host range, spanning across all six biological kingdoms (bacteria, fungi, plantae, animalia, archaea and protista) and viruses. The primary discoveries include the first Tn630 member—Tn630-NC1 and the closest homolog of IS630 from viruses—Tc1-C#1. By incorporating our discoveries into existing knowledge, we proposed a model to elucidate the formation of composite transposons. Organization of Tc1 and IS630 members into groups across biological kingdoms facilitates data collection for future research, particularly on their horizontal transfer between different kingdoms. The formation of composite transposons may result from asymmetric of terminal inverted repeats. IS630 should be merged with Tc1 into a single family IS630/Tc1. Furthermore, IS630 and its homologs constitute a valuable resource for studying horizontal gene transfer between gut bacteria and phages, opening up new avenues for research in this field.

Abstract Many epithermal gold and gold-rich porphyry-type ore deposits are associated with potassic magmas. Hence, potassic magmas are commonly assumed to have been unusually Au-rich or to have contained high Au/Cu ratios. However, these hypotheses remain poorly tested. Here, we report Au concentrations and Au/Cu ratios in silicate melt inclusions analyzed in potassic rocks worldwide. The results suggest that mafic potassic magmas generally contain only 2‒7 ng/g Au, despite common sulfide exhaustion during partial mantle melting. Both the absolute Au concentrations and Au/Cu ratios are comparable to those of mafic calc-alkaline magmas, and they vary little during subsequent magma differentiation because magmatic sulfide precipitation is strongly dominated by monosulfide solid solution that is relatively poor in Au and Cu. We thus suggest that the close association of Au-rich deposits with potassic magmas is not due to Au enrichment in the magma, but rather due to selective Au precipitation at the hydrothermal stage.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its genetic and geographical origins remain unclear, resulting in suspicions about its natural origin. In one of our previous studies, we reported the presence of a furin cleavage site RRAR in the junction region between S1 and S2 subunits of the spike protein, which was discovered as the first crucial clue for the origin tracing of SARS-CoV-2. In the present study, we conducted an integrative analysis of new genome data from bat Sarbecovirus strains reported after the COVID-19 outbreak. The primary results included the identification of BANAL-20-52, Rp22DB159, and S18CXBatR24 as three close relatives of SARS-CoV-2 and the successful detection of seven out of nine key genomic features (designated as RC0-7 and ORF8) observed in wild types of SARS-CoV-2 in the three close relatives from Laos, Vietnam, and Yunnan province of China, respectively. The most significant contribution of the present study lies in the detection of RC1 in wild genotype in a bat Sarbecovirus population BANAL-20-52 belonging to. Encoding a segment of the NSP3 protein, RC1 was discovered as the second crucial clue for the origin tracing of SARS-CoV-2. Although RC0, encoding the junction furin cleavage site, remains undetected outside of the SARS-CoV-2 genome, Feuang of Laos is the sole place where eight of the nine wild-type features (RC1-7 and ORF8) have been detected.

Abstract In recent years, the rapid development of nanotechnology has made significant impacts on the industry. With the wide application of nanotechnology, nanoparticles (NPs) are inevitably released into the environment, and their fate, behavior and toxicity are indeterminate. Studies have indicated that NPs can be absorbed, transported and accumulated by terrestrial plants. The presence of NPs in certain edible plants may decrease harvests and threaten human health. Understanding the transport and toxicity of NPs in plants is the basis for risk assessment. In this review, we summarize the transportation of four types of NPs in terrestrial plants, and the phytotoxicity induced by NPs, including their impacts on plant growth and cell structure, and the underlying mechanisms such as inducing oxidative stress response, and causing genotoxic damage. We expect to provide reference for future research on the effects of NPs on plants. Graphical Abstract

Water leakages can affect the safety and durability of shield tunnels, so rapid and accurate identification and diagnosis are urgently needed. However, current leakage detection methods are mostly based on mobile LiDAR data, making it challenging to detect leakage damage in both mobile and terrestrial LiDAR data simultaneously, and the detection results are not intuitive. Therefore, an integrated cylindrical voxel and Mask R-CNN method for water leakage inspection is presented in this paper. This method includes the following three steps: (1) a 3D cylindrical-voxel data organization structure is constructed to transform the tunnel point cloud from disordered to ordered and achieve the projection of a 3D point cloud to a 2D image; (2) automated leakage segmentation and localization is carried out via Mask R-CNN; (3) the segmentation results of water leakage are mapped back to the 3D point cloud based on a cylindrical-voxel structure of shield tunnel point cloud, achieving the expression of water leakage disease in 3D space. The proposed approach can efficiently detect water leakage and leakage not only in mobile laser point cloud data but also in ground laser point cloud data, especially in processing its curved parts. Additionally, it achieves the visualization of water leakage in shield tunnels in 3D space, making the water leakage results more intuitive. Experimental validation is conducted based on the MLS and TLS point cloud data collected in Nanjing and Suzhou, respectively. Compared with the current commonly used detection method, which combines cylindrical projection and Mask R-CNN, the proposed method can achieve water leakage detection and 3D visualization in different tunnel scenarios, and the accuracy of water leakage detection of the method in this paper has improved by nearly 10%.

BackgroundHot flashes are common symptoms afflicting perimenopausal women. A stellate ganglion block (SGB) is believed to be an effective treatment for hot flashes; however, more evidence is needed to evaluate its safety and efficacy in relieving perimenopausal hot flashes.ObjectiveTo investigate the efficacy and safety of SGB for the treatment of perimenopausal hot flashes.MethodsA randomized controlled trial was conducted at Shanxi Bethune Hospital. Forty perimenopausal women with hot flashes were recruited from April 2022 to November 2022 and randomly assigned to receive either 6 consecutive SGB treatments or 6 consecutive saline placebo treatments. The primary outcome was the change in hot flash symptom score from baseline to 12 weeks after treatment. The secondary outcomes were the change in hot flash symptom score from baseline to 12 weeks after treatment and the post-treatment Kupperman Index (KI) and Pittsburgh Sleep Quality Index (PSQI) scores.ResultsOf the 40 randomized subjects, 35 completed the study. All the variables were significantly improved. During 12 weeks of follow-up, the hot flash scores, Kupperman Menopause Scale scores, and Pittsburgh Sleep Quality Scale scores decreased significantly. Two subjects in the SGB treatment group experienced transient hoarseness, and the incidence of related adverse events was 10%. No related adverse events occurred in the control group.ConclusionCompared to the control treatment, SGB treatment was a safe and effective nonhormone replacement therapy that significantly relieved perimenopausal hot flashes and effectively improved sleep quality. Additional studies are needed to assess the long-term efficacy of this therapy.

BackgroundIdentification of transposons without close homologs is still a difficult task. IS630/Tc1/mariner transposons, classified into a superfamily, are probably the most widespread DNA transposons in nature. Tc1/mariner transposons have been discovered in animals, plants, and filamentous fungi, however, not in yeast.ResultsIn the present study, we report the discovery of two intact Tc1 transposons in yeast and filamentous fungi, respectively. The first one, named Tc1-OP1 (DD40E), represents Tc1 transposons in Ogataea parapolymorpha. The second one, named Tc1-MP1 (DD34E), represents Tc1 transposons in the Rhizopodaceae and Mucoraceae families. As a homolog of Tc1-OP1 and Tc1-MP1, IS630-AB1 (DD34E) was discovered as an IS630 transposon in Acinetobacter spp.ConclusionTc1-OP1 is not only the first reported Tc1 transposon in yeast, but also the first reported nonclassical Tc1 transposon. Tc1-OP1 is the largest of IS630/Tc1/mariner transposons reported to date and significantly different from others. Notably, Tc1-OP1 encodes a serine-rich domain and a transposase, extending the current knowledge of Tc1 transposons. The phylogenetic relationships of Tc1-OP1, Tc1-MP1 and IS630-AB1 indicated that these transposons had evolved from a common ancestor. Tc1-OP1, Tc1-MP1 and IS630-AB1 can be used as reference sequences to facilitate the identification of IS630/Tc1/mariner transposons. More Tc1/mariner transposons will be identified in yeast, following our discovery.

Abstract Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors. To overcome these issues, we developed a cell- and growth factor-free approach to induce bone formation in a critical-size bone defect by using an interconnected porous beta-tricalcium phosphate (β-TCP) scaffold with multiple channels. In vitro cell experimental results showed that multiple channels significantly promoted cell attachment and proliferation of human bone marrow mesenchymal stem cells, stimulated their alkaline phosphatase activity, and up-regulated the osteogenic gene expression. Multiple channels also considerably stimulated the expression of various mechanosensing markers of the cells, such as focal adhesion kinase, filamentous actin, and Yes-associated protein-1 at both static and dynamic culturing conditions. The in vivo bone defect implantation results demonstrated more bone formation inside multiple-channeled scaffolds compared to non-channeled scaffolds. Multiple channels prominently accelerated collagen type I, bone sialoprotein and osteocalcin protein expression. Fluorochrome images and angiogenic marker CD31 staining exhibited more mineral deposition and longer vasculature structures in multiple-channeled scaffolds, compared to non-channeled scaffolds. All the findings suggested that the creation of interconnected multiple channels in the porous β-TCP scaffold is a very promising approach to promote bone tissue regeneration.

Objective To compare the long-term outcomes of MWA as the first-line treatment for HCC in peribiliary versus non-peribiliary locations using propensity score matching analysis. Methods The study participants were recruited between April 2012 and October 2016. In total, 236 patients with HCC

BackgroundCurrently, methylotrophic yeasts (e.g., Pichia pastoris, Ogataea polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains-CBS4732, NCYC495, and DL-1. However, the relationship between CBS4732, NCYC495, and DL-1 remains unclear, as the genomic differences between them have not be exactly determined without their high-quality complete genomes. As a nutritionally deficient mutant derived from CBS4732, the O. polymorpha strain CBS4732 ura3Δ (named HU-11) is being used for high-yield production of several important proteins or peptides. HU-11 has the same reference genome as CBS4732 (noted as HU-11/CBS4732), because the only genomic difference between them is a 5-bp insertion.ResultsIn the present study, we have assembled the full-length genome of O. polymorpha HU-11/CBS4732 using high-depth PacBio and Illumina data. Long terminal repeat retrotransposons (LTR-rts), rDNA, 5′ and 3′ telomeric, subtelomeric, low complexity and other repeat regions were exactly determined to improve the genome quality. In brief, the main findings include complete rDNAs, complete LTR-rts, three large duplicated segments in subtelomeric regions and three structural variations between the HU-11/CBS4732 and NCYC495 genomes. These findings are very important for the assembly of full-length genomes of yeast and the correction of assembly errors in the published genomes of Ogataea spp. HU-11/CBS4732 is so phylogenetically close to NCYC495 that the syntenic regions cover nearly 100% of their genomes. Moreover, HU-11/CBS4732 and NCYC495 share a nucleotide identity of 99.5% through their whole genomes. CBS4732 and NCYC495 can be regarded as the same strain in basic research and industrial applications.ConclusionThe present study preliminarily revealed the relationship between CBS4732, NCYC495, and DL-1. Our findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha CBS4732, NCYC495, DL-1, and their derivative strains. The full-length genome of O. polymorpha HU-11/CBS4732 should be included into the NCBI RefSeq database for future studies of Ogataea spp.

Milk and dairy products are sources of exposure to estrogenic endocrine disrupting compounds (e-EDCs). Estrogenic disruptors can accumulate in organisms through the food chain and may negatively affect ecosystems and organisms even at low concentrations. Therefore, the analysis of e-EDCs in dairy products is of practical significance. Continuous efforts have been made to establish effective methods to detect e-EDCs, using convenient sample pretreatments and simple steps. This review aims to summarize the recently reported pretreatment methods for estrogenic disruptors, such as solid-phase extraction (SPE) and liquid phase microextraction (LPME), determination methods including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), Raman spectroscopy, and biosensors, to provide a reliable theoretical basis and operational method for e-EDC analysis in the future.

Abstract The review aimed at assessing the osteopromotive potential as well as soft tissue and temporomandibular joint (TMJ) cartilage healing properties of simvastatin by summarizing its efficacy on the current dental treatment of periodontal bone and soft tissue defects, and temporomandibular joint (TMJ) arthritis from the available animals and human studies. An electronic search was performed on MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) using a combination of keywords. A hand search was undertaken on seven oral surgery journals. No limitation of publication year in the English language was placed. Controlled randomized animal and human clinical trials, as well as prospective comparative studies, were included. Data on the comparison of topical/systemic simvastatin on bone healing in intrabony and furcation defects, extraction sockets, distraction osteogenesis, as well as soft tissue healing in mucogingival grafting procedures and cartilage protection in TMJ arthritis were extracted from all the eligible studies. Studies with a minimum of ten participants and follow up at least 6 months were included. Ten animal studies and six clinical studies were included in this study. All the animal studies included a minimum of eight sites per group assessed clinically, histologically, and radiographically. All human studies included clinical and radiological evaluation. The results of the review show that simvastatin administration displays positive treatment outcomes in the full range of therapies investigated in the oral regions such as periodontal infection control, periodontal and alveolar bone regeneration, soft tissue grafting, TMJ inflammation reduction, and cartilage repair. Its mechanism includes stimulating bone formation, promoting soft tissue healing, increasing articular and condylar cartilage thickness, as well as reducing inflammation at surgical sites in TMJ disorders. Simvastatin administration is beneficial to the healing of oral bone and cartilage. More studies are desired to determine its potential in soft tissue healing.

Abstract Purpose The aim of this study was to evaluate the role of mesh technique in the reconstruction of the extensor mechanism after resection of proximal tibial tumors. Methods We retrospectively analyzed the cases of 14 patients who were diagnosed with proximal tibial tumors at our center and reconstructed with tumor prosthesis, gastrocnemius muscle, and mesh between 2012 and 2017. The treatment strategies for patellar tendon reconstruction primarily involve gastrocnemius reconstruction to cover the tumor prosthesis and mesh reconstruction for the patellar ligament. Results Among the 14 patients, the mean was 1.57° (range 0–12°) for active extension versus 105.00° (range 80–120°) for active flexion. The mean for passive extension was 0°. The passive flexion mean was 115.00° (range 90–120°). The extensor lag averaged 1.57° (range 0–12°), and the mean Musculoskeletal Tumor Society score (MSTS) was 23.57 (range 19–27). The average follow-up for all patients was 23.50 months (range 14–37). During the recent follow-up, all patients were able to walk without crutches. Two patients underwent above-the-knee amputation for local recurrence of the tumor, and lung metastasis occurred in three patients after operation. There were no postoperative complications. Conclusions Extensor lag was remarkably reduced in the surgery group in comparison to previous study reports. Surgical resection is a simple, reliable, and effective method to remove and control the tumor. Mesh reconstruction of patellar ligament is effective to reconstruct the extensor mechanism of the knee after excision of tumor.

Epithelial–mesenchymal transition (EMT) is implicated in tumor metastasis and therapeutic resistance. It remains a challenge to target cancer cells that have undergone EMT. The Snail family of key EMT-inducing transcription factors directly binds to and transcriptionally represses not only epithelial genes but also a myriad of additional genomic targets that may carry out significant biological functions. Therefore, we reasoned that EMT inherently causes various concomitant phenotypes, some of which may create targetable vulnerabilities for cancer treatment. In the present study, we found that Snail transcription factors bind to the promoters of multiple genes encoding subunits of the AMP-activated protein kinase (AMPK) complex, and expression of AMPK genes was markedly downregulated by EMT. Accordingly, high AMPK expression in tumors correlated with epithelial cell markers and low AMPK expression in tumors was strongly associated with adverse prognosis. AMPK is the principal sensor of cellular energy status. In response to energy stress, AMPK is activated and critically reprograms cellular metabolism to restore energy homeostasis and maintain cell survival. We showed that activation of AMPK by energy stress was severely impaired by EMT. Consequently, EMT cancer cells became hypersensitive to a variety of energy stress conditions and primarily underwent pyroptosis, a regulated form of necrotic cell death. Collectively, the study suggests that EMT impedes the activation of AMPK signaling induced by energy stress and sensitizes cancer cells to pyroptotic cell death under energy stress conditions. Therefore, while EMT promotes malignant progression, it concurrently induces collateral vulnerabilities that may be therapeutically exploited.

In December 2019, the world awoke to a new betacoronavirus strain named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Betacoronavirus consists of A, B, C and D subgroups. Both SARS-CoV and SARS-CoV-2 belong to betacoronavirus subgroup B. In the present study, we divided betacoronavirus subgroup B into the SARS1 and SARS2 classes by six key insertions and deletions (InDels) in betacoronavirus genomes, and identified a recently detected betacoronavirus strains RmYN02 as a recombinant strain across the SARS1 and SARS2 classes, which has potential to generate a new strain with similar risk as SARS-CoV and SARS-CoV-2. By analyzing genomic features of betacoronavirus, we concluded: (1) the jumping transcription and recombination of CoVs share the same molecular mechanism, which inevitably causes CoV outbreaks; (2) recombination, receptor binding abilities, junction furin cleavage sites (FCSs), first hairpins and ORF8s are main factors contributing to extraordinary transmission, virulence and host adaptability of betacoronavirus; and (3) the strong recombination ability of CoVs integrated other main factors to generate multiple recombinant strains, two of which evolved into SARS-CoV and SARS-CoV-2, resulting in the SARS and COVID-19 pandemics. As the most important genomic features of SARS-CoV and SARS-CoV-2, an enhanced ORF8 and a novel junction FCS, respectively, are indispensable clues for future studies of their origin and evolution. The WIV1 strain without the enhanced ORF8 and the RaTG13 strain without the junction FCS “RRAR” may contribute to, but are not the immediate ancestors of SARS-CoV and SARS-CoV-2, respectively.

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription of SARS-CoV-2 has recently emerged, their regulation remains unknown.ResultsBy comprehensive analysis of genome sequence and protein structure data, we propose a negative feedback model to explain the regulation of CoV replication and transcription, providing a molecular basis of the “leader-to-body fusion” model. The key step leading to the proposal of our model was that the transcription regulatory sequence (TRS) motifs were identified as the cleavage sites of nsp15, a nidoviral RNA uridylate-specific endoribonuclease (NendoU). According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs), and genomic RNAs (gRNAs) by cleaving TRSs. The expression level of nsp15 controls the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nsp15 to reach equilibrium between the CoV replication and transcription.ConclusionThe replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g., uridine derivatives) against CoVs.

Titanium hypersensitivity is rare, but it may exist among patients who need dental implant treatment. It could contribute to mild or severe peri-implant tissue hypersensitivity reactions and affect patients’ oral and general health according to some clinical reports. In extreme cases, it may lead to implant failure or extraction. In this case report, a 64-year-old Caucasian female patient received a titanium implant placement on #5. Right after the implant placement, she reported the symptoms of pain, eczema, and slight extraoral swelling, along with significant burning sensation occurring intra- and extraorally. The symptoms were not released after the systemic intervention of antibiotics for six days. On retrieving her medical history, the patient reported a previous allergic reaction to jewelry-like earrings in her childhood. The diagnosis of titanium hypersensitivity was made based on the rapid onset of symptoms and her metal allergy history. Therefore, the dental implant was removed after diagnosis, and a bone allograft was used to preserve the alveolar bone volume. Immediately after implant extraction, the swelling and burning sensation were receded. A complete recovery was achieved three weeks later. The dimension of the alveolar ridge bone was found well maintained in 10 weeks follow-up visit. Conclusion. Rapid onset of peri-implant gingival swelling may indicate a hypersensitivity to titanium implant in the clinic. For patients with a history of allergy to jewelry, the hypersensitivity tests to titanium alloy such as patch test or lymphocyte transformation test should be recommended as part of the dental implant treatment plan.

Telmisartan, an angiotensin II type 1–receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aβ42, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain. Keywords:: type 1 diabetes, telmisartan, memory, amyloidosis

The pore, crystal structure, and electrochemical performance of mesoporous MnO2 prepared by silica sol template method as electrode material for supercapacitor were investigated in this work. It is found that the crystal structure of nonporous and mesoporous MnO2 is confirmed to be β-MnO2 and the crystallinity of mesoporous MnO2 decreases due to the formation of mesopore. The results of electrochemical performance show that the specific capacitances of the sample prepared by using 20 g of Mn(NO3)2 solution and 40 g of silica sol (named MMO-4) at the scan rate of 5 mV/s are the highest (163.2 F/g), in comparison with 19.3 F/g of that of the sample of blank, suggesting the important role of pore-forming using silica sol as template. As the potential scan rate is raised to 200 mV/s, the specific capacitances of the sample of blank and MMO-4 are 12.2 F/g and 21.6 F/g, respectively. The great improvement of specific capacitance is probably due to the enlarged activated surface area after template is added.