Sulfadiazine degradation by Bjerkandera adusta DH0817 at low temperatures and its cold-adaptation mechanisms.

The prolonged period of low temperatures in northern China poses a significant challenge to the bioremediation of antibiotic pollution. This study reports that a white-rot fungus Bjerkandera adusta DH0817, isolated from a poultry farm in Liaoning Province, can remove 60 % of SDZ within 20 days at 10℃ and reduce the biotoxicity of SDZ. Six degradation pathways were proposed. SDZ biodegradation was primarily driven by cytochrome P450. Transcriptome analysis revealed that DH0817 upregulated genes associated with cell membrane, transcription factors and soluble sugars in response to low temperatures. Subsequently, genes associated with fatty acid, proteins and enzymes were upregulated to remove SDZ at low temperatures. This study provides valuable microbial resources and serves as a theoretical reference for addressing antibiotic pollution in livestock and poultry farms under low temperature conditions.

Analysis of three primary prostatic sarcoma cases and literature review.

OBJECTIVE: The objective of this study is to evaluate the clinical presentations, diagnostic approaches, and treatment modalities for primary prostate sarcoma postradical prostatectomy, aiming to enhance its diagnosis and management. METHODS: We retrospectively reviewed the clinical records of three male patients diagnosed with primary prostate sarcoma at Beijing Chaoyang Hospital, affiliated with Capital Medical University, from February 2014 to February 2024. All patients underwent transrectal prostate biopsies, which informed the decision to proceed with laparoscopic radical prostatectomies. After surgery, one patient received a combination of epirubicin and ifosfamide as immunotherapy, along with external beam radiotherapy. After comprehensive discussions regarding potential benefits and risks, the remaining two patients decided against undergoing radiotherapy and chemotherapy. RESULTS: Based on the pathological examination results, two patients were diagnosed with stromal sarcoma and one with spindle cell sarcoma, all classified as high-grade sarcomas. Immunohistochemical analysis showed that all three cases were positive for VIMENTIN, but other results did not show significant specificity. During the follow-up period, one patient died within 12 months, and two patients were lost to follow-up after 6 months. However, there were no evident signs of recurrence observed during the follow-up period. CONCLUSIONS: Primary prostate sarcoma is extremely rare and typically has a poor prognosis once diagnosed. Early diagnosis should be based on pathological and immunohistochemical testing results, followed by prompt surgical treatment and adjuvant radiotherapy and chemotherapy. Despite these measures, recurrence is common, underscoring the need for a detailed and appropriate treatment plan and systematic therapy for affected patients.

Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial.

BACKGROUND: Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction. METHODS: Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study's primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle. DISCUSSION: The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery. TRIAL REGISTRATION: ChiCTR2200064041, registered on 24th September, 2022.

Genomic structural variation contributes to evolved changes in gene expression in high-altitude Tibetan sheep.

Tibetan sheep were introduced to the Qinghai Tibet plateau roughly 3,000 B.P., making this species a good model for investigating genetic mechanisms of high-altitude adaptation over a relatively short timescale. Here, we characterize genomic structural variants (SVs) that distinguish Tibetan sheep from closely related, low-altitude Hu sheep, and we examine associated changes in tissue-specific gene expression. We document differentiation between the two sheep breeds in frequencies of SVs associated with genes involved in cardiac function and circulation. In Tibetan sheep, we identified high-frequency SVs in a total of 462 genes, including EPAS1, PAPSS2, and PTPRD. Single-cell RNA-Seq data and luciferase reporter assays revealed that the SVs had cis-acting effects on the expression levels of these three genes in specific tissues and cell types. In Tibetan sheep, we identified a high-frequency chromosomal inversion that exhibited modified chromatin architectures relative to the noninverted allele that predominates in Hu sheep. The inversion harbors several genes with altered expression patterns related to heart protection, brown adipocyte proliferation, angiogenesis, and DNA repair. These findings indicate that SVs represent an important source of genetic variation in gene expression and may have contributed to high-altitude adaptation in Tibetan sheep.

An Ester-Functionalized Bidentate Titanium-based Metal-Organic Framework with Visible-Light Enhanced Activity for CO2 Photoreduction.

The limited visible light response is a critical drawback that hampers the photocatalytic efficacy of Ti-MOFs. However, study concerning the enhancement of the visible-light response of Ti-MOFs is still in its nascent stage. In this study, we employ the 'dual-ligand decrystallization strategy' to manipulate the electronic environment of Ti4+, leading to the synthesis of three ester-functionalized bidentate Ti-MOFs with enhanced visible light response. Our findings reveal that this approach not only reduces the bandgap of Ti-MOFs but also enhances their photocatalytic activity for carbon dioxide reduction. Specifically, compared to the bandgap of Ti-BPDC at 2.98 eV, the bandgap of Ti-BPDC-CA 1:2 has been reduced to 2.14 eV. Moreover, Ti-BPDC-CA 1:2 exhibits extraordinary photocatalytic activity with the formic acid (HCOOH) production rate of 617 µmol g-1 h-1 with over 99.5% selectivity, which is 3.47 times higher than that of Ti-BPDC. Besides providing a cost-effective strategy for enhancing the visible light response of Ti-MOFs, our study also serves as an illustrative example for establishing the correlation between electronic structure and optical properties.

A Retrospective Cohort Study of vNOTES Extraperitoneal Versus Laparoscopic Sacral Hysteropexy With Uterine Preserving Regarding Surgical Outcomes and Two-Year Follow-Up Results.

STUDY OBJECTIVE: To explore the effectiveness of transvaginal natural orifice transluminal endoscopic surgery extraperitoneal sacral hysteropexy (vNOTES-ESH) in women with symptomatic uterine prolapse over a 2 year follow-up. DESIGN: Retrospective cohort study. SETTING: Gynecological minimally invasive center. PATIENTS: Women undergoing sacral hysteropexy either by vNOTES (n = 25) or laparoscopic (n = 74) between November 2016 and December 2020. INTERVENTIONS: Both vNOTES-ESH and laparoscopic sacral hysteropexy (LAP-SH) were used for uterine prolapse. Demographic data, operative characteristics, perioperative outcomes, and follow-up information 2 years postsurgery in the 2 groups were retrospectively evaluated. RESULTS: Both procedures showed similar operation time, estimated blood loss, hospital stays, and pain scores (p >0.05). During a median follow-up of 59 (24-72) months, the surgical success rate was 96% for vNOTES-ESH and 97.3% for LAP-SH (p >0.05), with no differences in anatomical position or pelvic organ function after the operation. Women in the LAP-SH group experienced more bothersome symptoms of constipation compared to those in the vNOTES-ESH group (5.41% vs 0, p <0.05). Lastly, 1 case in the vNOTES-ESH group had a mesh exposed area of less than 1 cm2, and 1 patient in the LAP-SH group experienced stress incontinence. CONCLUSIONS: In this retrospective study, vNOTES-ESH met our patients' preference for uterine preservation and was a successful and effective treatment for uterine prolapse, providing good functional improvement in our follow-up. This procedure should be considered as an option for patients with pelvic organ prolapse.

FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner.

Gastric cancer (GC) is a serious malignant tumour with a high mortality rate and a poor prognosis. Recently, emerging evidence has suggested that N6-methyladenosine (m6A) modification plays a crucial regulatory role in cancer progression. However, the exact role of m6A regulatory factors FTO in GC is unclear. First, the expression of m6A methylation-related regulatory factors in clinical samples and the clinical data of the corresponding patients were obtained from The Cancer Genome Atlas (TCGA-STAD) dataset, and correlation analysis between FTO expression and patient clinicopathological parameters was subsequently performed. qRT-PCR, immunohistochemistry (IHC) and western blotting (WB) were used to verify FTO expression in GC. CCK-8, EdU, flow cytometry and transwell assays were used to evaluate the effect of FTO on the behaviour of GC cells. Transcriptome sequencing and RNA immunoprecipitation analysis were used to explore the potential regulatory mechanisms mediated by FTO. FTO was highly expressed in GC tissues and cells, and high expression of FTO predicted a worse prognosis than low expression. Functionally, overexpression of FTO promoted the proliferation, migration and invasion of GC cells but inhibited cell apoptosis. Mechanistically, we found that FTO is upregulated in GC and promotes GC progression by modulating the expression of MAP4K4. Taken together, our findings provide new insights into the effects of FTO-mediated m6A demethylation and could lead to the development of new strategies for GC monitoring and aggressive treatment.

Regulation of CTLs/Tregs via Highly Stable and Ultrasound-Responsive Cerasomal Nano-Modulators for Enhanced Colorectal Cancer Immunotherapy.

Immunotherapy is showing good potential for colorectal cancer therapy, however, low responsive rates and severe immune-related drug side effects still hamper its therapeutic effectiveness. Herein, a highly stable cerasomal nano-modulator (DMC@P-Cs) with ultrasound (US)-controlled drug delivery capability for selective sonodynamic-immunotherapy is fabricated. DMC@P-Cs' lipid bilayer is self-assembled from cerasome-forming lipid (CFL), pyrophaeophorbid conjugated lipid (PL), and phospholipids containing unsaturated chemical bonds (DOPC), resulting in US-responsive lipid shell. Demethylcantharidin (DMC) as an immunotherapy adjuvant is loaded in the hydrophilic core of DMC@P-Cs. With US irradiation, reactive oxygen species (ROS) can be effectively generated from DMC@P-Cs, which can not only kill tumor cells for inducing immunogenic cell death (ICD), but also oxidize unsaturated phospholipids-DOPC to change the permeability of the lipid bilayers and facilitate controlled release of DMC, thus resulting in down-regulation of regulatory T cells (Tregs) and amplification of anti-tumor immune responses. After intravenous injection, DMC@P-Cs can efficiently accumulate at the tumor site, and local US treatment resulted in 94.73% tumor inhibition rate. In addition, there is no detectable systemic toxicity. Therefore, this study provides a highly stable and US-controllable smart delivery system to achieve synergistical sonodynamic-immunotherapy for enhanced colorectal cancer therapy.

YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation.

BACKGROUND: N6-methyladenosine (m6A) modification is one of the most common RNA modifications in mammals. m6A modification, and associated abnormal gene expression, occur during various biological processes, most notably tumorigenesis. YTH domain-containing family protein 1 (YTHDF1), a m6A reader, bind to messenger RNAs (mRNAs) containing a m6A modification and this enhances its interaction with the ribosome and promotes translation. The function of YTHDF1 in gastric cancer (GC) has been the subject of earlier studies; however, the precise mechanism underlying YTHDF1's role in GC has not been fully elucidated. METHODS: The expression of YTHDF1 was evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting. CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays were utilized to explore the effect of YTHDF1 on GC cell viability and proliferation. Transcriptome sequencing and RNA immunoprecipitation assays were utilized to explore the underlying mechanisms mediated by YTHDF1. RESULTS: We observed that YTHDF1 is upregulated in GC cancer tissues. Knockdown of YTHDF1 in GC cells significantly inhibited proliferation and promoted apoptosis, suggesting that YTHDF1 increases proliferation and blocks apoptosis in GC cells. Mechanistically, data gathered suggest that YTHDF1 promotes the translation of the transcription factor TCF7 and this results in activation of the WNT signaling axis. CONCLUSIONS: We found that YTHDF1 was upregulated in GC and that YTHDF1 could promote GC progression through modulating the translational efficiency of TCF7. Taken together, these findings may provide a novel therapeutic target for GC.

MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3.

OBJECTIVES: The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. METHODS: The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. RESULTS: miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-ß1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. CONCLUSION: Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal hypovascular tumor surrounded by dense fibrosis. Albumin-bound paclitaxel and gemcitabine (AG) chemotherapy is the mainstay of PDAC treatment through depleting peritumoral fibrosis and killing tumor cells; however, it remains challenging due to the lack of a noninvasive imaging method evaluating fibrotic changes during AG chemotherapy. In this study, we developed a dual-modality imaging platform that enables noninvasive, dynamic, and quantitative assessment of chemotherapy-induced fibrotic changes through near-infrared fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) using an extradomain B fibronectin (EDB-FN)-targeted imaging probe (ZD2-Gd-DOTA-Cy7). METHODS: The ZD2-Gd-DOTA-Cy7 probe was constructed by conjugating a peptide (Cys-TVRTSAD) to Gd-DOTA and the near-infrared dye Cy7. PDAC murine xenograft models were intravenously injected with ZD2-Gd-DOTA-Cy7 at a Gd concentration of 0.05 mmol/kg or free Cy7 and Gd-DOTA as control. The normalized tumor background ratio (TBR) on FMI and the T1 reduction ratio on MRI were quantitatively analyzed. For models receiving AG chemotherapy or saline, MRI/FMI was performed before and after treatment. Histological analyses were performed for validation. RESULTS: The ZD2-Gd-DOTA-Cy7 concentration showed a linear correlation with the fluorescence intensity and T1 relaxation time in vitro. The optimal imaging time was 30 min after injection of the ZD2-Gd-DOTA-Cy7 (0.05 mmol/kg), only half of the clinic dosage of gadolinium. Additionally, ZD2-Gd-DOTA-Cy7 generated a 1.44-fold and 1.90-fold robust contrast enhancement compared with Cy7 (P < 0.05) and Gd-DOTA (P < 0.05), respectively. For AG chemotherapy monitoring, the T1 reduction ratio and normalized TBR in the fibrotic tumor areas were significantly increased by 1.99-fold (P < 0.05) and 1.78-fold (P < 0.05), respectively, in the control group compared with those in the AG group. CONCLUSION: MRI/FMI with a low dose of ZD2-Gd-DOTA-Cy7 enables sensitive imaging of PDAC and the quantitative assessment of fibrotic changes during AG chemotherapy, which shows potential clinical applications for precise diagnosis, post-treatment monitoring, and disease management.

A One-Stone-Two-Birds Strategy of Targeting Microbubbles with "Dual" Anti-Inflammatory and Blood-Brain Barrier "Switch" Function for Ischemic Stroke Treatment.

Inflammation is considered to be the main target of the development of new stroke therapies. There are three key issues in the treatment of stroke inflammation: the first one is how to overcome the blood-brain barrier (BBB) to achieve drug delivery, the second one is how to select drugs to treat stroke inflammation, and the third one is how to achieve targeted drug delivery. In this study, we constructed hydrocortisone-phosphatidylserine microbubbles and combined them with ultrasound (US)-targeted microbubble destruction technology to successfully open the BBB to achieve targeted drug delivery. Phosphatidylserine on the microbubbles was used for its "eat me" effect to increase the targeting of the microvesicles. In addition, we found that hydrocortisone can accelerate the closure of the BBB, achieving efficient drug delivery while reducing the entry of peripheral toxins into the brain. In the treatment of stroke inflammation, it was found that hydrocortisone itself has anti-inflammatory effects and can also change the polarization of microglia from the harmful pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype, thus achieving dual anti-inflammatory effects and enhancing the anti-inflammatory effects in ischemic areas after stroke, well reducing the cerebellar infarction volume by inhibiting the inflammatory response after cerebral ischemia. A confocal microendoscope was used to directly observe the polarization of microglial cells in living animal models for dynamic microscopic visualization detection showing the advantage of being closer to clinical work. Taken together, this study constructed a multifunctional targeted US contrast agent with the function of "one-stone-two-birds", which can not only "on-off" the BBB but also have "two" anti-inflammatory functions, providing a new strategy of integrated anti-inflammatory targeted delivery and imaging monitoring for ischemic stroke treatment.

The bZIP transcription factor MpbZIP9 regulates anthocyanin biosynthesis in Malus 'Pinkspire' fruit.

Malus 'Pinkspire' is regulated by abscisic acid (ABA), which results in a red colour, but the regulatory relationship between ABA and anthocyanin synthesis has not been determined. The key factors affecting the colour change of M. 'Pinkspire' peel were investigated during the periods of significant colour changes during fruit ripening. The results showed that the transcription factor MpbZIP9 associated with ABA was screened by transcriptomic analysis. MpbZIP9 expression was consistent with the trend of structural genes expression for anthocyanin synthesis in the peel during fruit ripening, as well as with changes in the content of ABA, which is a positive regulator. A yeast one-hybrid assay showed that MpbZIP9 can directly bind to the promoter of MpF3'H. Dual luciferase reporter gene assays and GUS staining experiments showed that MpbZIP9 significantly activate MpF3'H expression. In addition, overexpression of the MpbZIP9 significantly enhanced anthocyanin accumulation and the expression of genes involved in anthocyanin synthesis. In contrast, virus-induced silencing of the MpbZIP9 significantly reduced the expression of structural genes involved in anthocyanin synthesis. These results suggest that the MpbZIP9 transcription factor can regulate the synthesis of peel anthocyanin and is a positive regulator that promotes anthocyanin biosynthesis by activating MpF3'H expression.

An EBV-related CD4 TCR immunotherapy inhibits tumor growth in an HLA-DP5+ nasopharyngeal cancer mouse model.

Adoptive transfer of T cell receptor-engineered T cells (TCR-T) is a promising strategy for immunotherapy against solid tumors. However, the potential of CD4+ T cells in mediating tumor regression has been neglected. Nasopharyngeal cancer is consistently associated with EBV. Here, to evaluate the therapeutic potential of CD4 TCR-T in nasopharyngeal cancer, we screened for CD4 TCRs recognizing EBV nuclear antigen 1 (EBNA1) presented by HLA-DP5. Using mass spectrometry, we identified EBNA1567-581, a peptide naturally processed and presented by HLA-DP5. We isolated TCR135, a CD4 TCR with high functional avidity, that can function in both CD4+ and CD8+ T cells and recognizes HLA-DP5-restricted EBNA1567-581. TCR135-transduced T cells functioned in two ways: directly killing HLA-DP5+EBNA1+ tumor cells after recognizing EBNA1 presented by tumor cells and indirectly killing HLA-DP5-negative tumor cells after recognizing EBNA1 presented by antigen-presenting cells. TCR135-transduced T cells preferentially infiltrated into the tumor microenvironment and significantly inhibited tumor growth in xenograft nasopharyngeal tumor models. Additionally, we found that 62% of nasopharyngeal cancer patients showed 50%-100% expression of HLA-DP on tumor cells, indicating that nasopharyngeal cancer is well suited for CD4 TCR-T therapy. These findings suggest that TCR135 may provide a new strategy for EBV-related nasopharyngeal cancer immunotherapy in HLA-DP5+ patients.

Metformin-Mediated Fast Charge-Reversal Nanohybrid for Deep Penetration Piezocatalysis-Augmented Chemodynamic Immunotherapy of Cancer.

Immune checkpoint blockade (ICB) therapy still suffers from insufficient immune response and adverse effect of ICB antibodies. Chemodynamic therapy (CDT) has been demonstrated to be an effective way to synergize with ICB therapy. However, a low generation rate of reactive oxygen species and poor tumor penetration of CDT platforms still decline the immune effects. Herein, a charge-reversal nanohybrid Met@BF containing both Fe3O4 and BaTiO3 nanoparticles in the core and Metformin (Met) on the surface was fabricated for tumor microenvironment (TME)- and ultrasound (US)-activated piezocatalysis-chemodynamic immunotherapy of cancer. Interestingly, Met@BF had a negative charge in blood circulation, which was rapidly changed into positive when exposed to acidic TME attributed to quaternization of tertiary amine in Met, facilitating deep tumor penetration. Subsequently, with US irradiation, Met@BF produced H2O2 based on piezocatalysis of BaTiO3, which greatly enhanced the Fenton reaction of Fe3O4, thus boosting robust antitumor immune response. Furthermore, PD-L1 expression was inhibited by the local released Met to further augment the antitumor immune effect, achieving effective inhibitions for both primary and metastatic tumors. Such a combination of piezocatalysis-enhanced chemodynamic therapy and Met-mediated deep tumor penetration and downregulation of PD-L1 provides a promising strategy to augment cancer immunotherapy.

Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy.

Immunotherapy as a milestone in cancer treatment has made great strides in the past decade, but it is still limited by low immune response rates and immune-related adverse events. Utilizing bioeffects of ultrasound to enhance tumor immunotherapy has attracted more and more attention, including sonothermal, sonomechanical, sonodynamic and sonopiezoelectric immunotherapy. Moreover, the emergence of nanomaterials has further improved the efficacy of ultrasound mediated immunotherapy. However, most of the summaries in this field are about a single aspect of the biological effects of ultrasound, which is not comprehensive and complete currently. This review proposes the recent progress of nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy. The concept of immunotherapy and the application of bioeffects of ultrasound in cancer immunotherapy are initially introduced. Then, according to different bioeffects of ultrasound, the representative paradigms of nanomaterial augmented sono-immunotherapy are described, and their mechanisms are discussed. Finally, the challenges and application prospects of nanomaterial augmented ultrasound mediated cancer immunotherapy are discussed in depth, hoping to pave the way for cancer immunotherapy and promote the clinical translation of ultrasound mediated cancer immunotherapy through the reasonable combination of nanomaterials augmented ultrasonic bioeffects.

Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors.

Zokors, an Asiatic group of subterranean rodents, originated in lowlands and colonized high-elevational zones following the uplift of the Qinghai-Tibet plateau about 3.6 million years ago. Zokors live at high elevation in subterranean burrows and experience hypobaric hypoxia, including both hypoxia (low oxygen concentration) and hypercapnia (elevated partial pressure of CO2). Here we report a genomic analysis of six zokor species (genus Eospalax) with different elevational ranges to identify structural variants (deletions and inversions) that may have contributed to high-elevation adaptation. Based on an assembly of a chromosome-level genome of the high-elevation species, Eospalax baileyi, we identified 18 large inversions that distinguished this species from congeners native to lower elevations. Small-scale structural variants in the introns of EGLN1, HIF1A, HSF1 and SFTPD of E. baileyi were associated with the upregulated expression of those genes. A rearrangement on chromosome 1 was associated with altered chromatin accessibility, leading to modified gene expression profiles of key genes involved in the physiological response to hypoxia. Multigene families that underwent copy-number expansions in E. baileyi were enriched for autophagy, HIF1 signalling and immune response. E. baileyi show a significantly larger lung mass than those of other Eospalax species. These findings highlight the key role of structural variants underlying hypoxia adaptation of high-elevation species in Eospalax.

Ultrasound-Controlled Delivery of Growth Factor-Loaded Cerasomes Combined with Polycaprolactone Scaffolds Seeded with Bone Marrow Mesenchymal Stem Cells for Biomimetic Tendon-to-Bone Interface Engineering.

Rotator cuff tear (RCT) is a prevalent shoulder injury that poses challenges for achieving continuous and functional regeneration of the tendon-to-bone interface (TBI). In this study, we controlled the delivery of growth factors (GFs) from liposomal nanohybrid cerasomes by ultrasound and implanted three-dimensional printed polycaprolactone (PCL) scaffolds modified with polydopamine loaded with bone marrow mesenchymal stem cells (BMSCs) to repair tears of the infraspinatus tendon in a lapine model. Direct suturing (control, CTL) was used as a control. The PCL/BMSC/cerasome (PBC) devices are sutured with the enthesis of the infraspinatus tendon. The cerasomes and PCL scaffolds are highly stable with excellent biocompatibility. The roles of GFs BMP2, TGFß1, and FGF2 in tissue-specific differentiation are validated. Compared with the CTL group, the PBC group had significantly greater proteoglycan deposition (P = 0.0218), collagen volume fraction (P = 0.0078), and proportions of collagen I (P = 0.0085) and collagen III (P = 0.0048). Biotin-labeled in situ hybridization revealed a high rate of survival for transplanted BMSCs. Collagen type co-staining at the TBI is consistent with multiple collagen regeneration. Our studies demonstrate the validity of biomimetic scaffolds of TBI with BMSC-seeded PCL scaffolds and GF-loaded cerasomes to enhance the treatment outcomes for RCTs.

Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia. METHODS: Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV). RESULTS: As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms. CONCLUSION: Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis. Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

Unraveling the functional instability of bacterial consortia in crude oil degradation via integrated co-occurrence networks.

Introduction: Soil ecosystems are threatened by crude oil contamination, requiring effective microbial remediation. However, our understanding of the key microbial taxa within the community, their interactions impacting crude oil degradation, and the stability of microbial functionality in oil degradation remain limited. Methods: To better understand these key points, we enriched a crude oil-degrading bacterial consortium generation 1 (G1) from contaminated soil and conducted three successive transfer passages (G2, G3, and G4). Integrated Co-occurrence Networks method was used to analyze microbial species correlation with crude oil components across G1-G4. Results and discussion: In this study, G1 achieved a total petroleum hydrocarbon (TPH) degradation rate of 32.29% within 10 days. Through three successive transfer passages, G2-G4 consortia were established, resulting in a gradual decrease in TPH degradation to 23.14% at the same time. Specifically, saturated hydrocarbon degradation rates ranged from 18.32% to 14.17% among G1-G4, and only G1 exhibited significant aromatic hydrocarbon degradation (15.59%). Functional annotation based on PICRUSt2 and FAPROTAX showed that functional potential of hydrocarbons degradation diminished across generations. These results demonstrated the functional instability of the bacterial consortium in crude oil degradation. The relative abundance of the Dietzia genus showed the highest positive correlation with the degradation efficiency of TPH and saturated hydrocarbons (19.48, 18.38, p < 0.05, respectively), Bacillus genus demonstrated the highest positive correlation (21.94, p < 0.05) with the efficiency of aromatic hydrocarbon degradation. The key scores of Dietzia genus decreased in successive generations. A significant positive correlation (16.56, p < 0.05) was observed between the Bacillus and Mycetocola genera exclusively in the G1 generation. The decline in crude oil degradation function during transfers was closely related to changes in the relative abundance of key genera such as Dietzia and Bacillus as well as their interactions with other genera including Mycetocola genus. Our study identified key bacterial genera involved in crude oil remediation microbiome construction, providing a theoretical basis for the next step in the construction of the oil pollution remediation microbiome.