Molecular characterization of a novel gammapartitivirus infecting the fungus Nigrospora oryzae.

Here, we identified a new mycovirus infecting the phytopathogenic fungus Nigrospora oryzae, which we have designated "Nigrospora oryzae partitivirus 2" (NoPV2). The genome of NoPV2 consists of two dsRNA segments (dsRNA 1 and dsRNA 2), measuring 1771 and 1440 bp in length, respectively. dsRNA 1 and dsRNA 2 each contain a single open reading frame (ORF) that encodes the RNA-dependent RNA polymerase (RdRp) and capsid protein (CP), respectively. A BLASTp search showed that the RdRp of NoPV2 had significant sequence similarity to the RdRps of other partitiviruses, including Nigrospora sphaerica partitivirus 1 (75.61% identity) and Magnaporthe oryzae partitivirus 1 (67.53% identity). Phylogenetic analysis revealed that NoPV2 is a new member of the genus Gammapartitivirus in the family Partitiviridae. This study provides important information for understanding the diversity of mycoviruses in N. oryzae.

Optimising wound care for patients with cirrhosis: A study of the effect of combination therapy on wound healing.

Cirrhosis, a chronic liver disease, significantly impairs wound healing due to complex alterations in physiology, including compromised immune function, poor nutritional status and altered blood flow. This prospective observational cohort study aimed to evaluate the effectiveness of the multidimensional combination therapy approach in enhancing wound healing among patients diagnosed with cirrhosis. The study was conducted from February to November 2023 in Shanghai, China, including 248 patients with cirrhosis experiencing poor wound healing. The combination therapy consisted of tailored pharmacological treatments, advanced wound dressings, dietitian-directed dietary regimens and supplementary therapies like negative pressure wound therapy (NPWT), stem cell and hyperbaric oxygen therapy. The interventions were customised based on comprehensive initial assessments of liver function, nutritional status and wound characteristics. Follow-ups were conducted to monitor response and adjust treatments accordingly. The patient demographic was varied, predominantly 41-60 years old, with the slight male predominance. The study demonstrated that after 3 months of treatment, wound sizes decreased significantly across all cirrhosis severity levels: mild (2.4-1.7 cm2 ), moderate (4.1-2.6 cm2 ) and severe (6.2-4.4 cm2 ). Healing rates improved to 90% in mild, 75% in moderate and 45% in severe cases over 6 months. Albumin levels increased by the average of +0.3 g/dL to +0.4 g/dL post-treatment across the severity spectrum. However, complication rates escalated with severity: Mild cases had a 10% infection rate, while severe cases had up to 30% infection rate. Combination therapy significantly improved wound healing in cirrhosis patients, with the extent of improvement correlated with the severity of the condition. Tailored, multidisciplinary approaches are critical in managing the intricate wound healing process in cirrhosis, effectively reducing healing times and improving overall treatment outcomes. These findings advocate for personalised care strategies and highlight the potential of integrating various treatment modalities to address the complex needs of this population.

Comparative transcriptome analysis reveals the regulatory mechanisms of two tropical water lilies in response to cold stress.

BACKGROUND: Tropical water lily is an aquatic plant with high ornamental value, but it cannot overwinter naturally at high latitudes. The temperature drop has become a key factor restricting the development and promotion of the industry. RESULTS: The responses of Nymphaea lotus and Nymphaea rubra to cold stress were analyzed from the perspective of physiology and transcriptomics. Under the cold stress, Nymphaea rubra had obvious leaf edge curling and chlorosis. The degree of peroxidation of its membrane was higher than that of Nymphaea lotus, and the content of photosynthetic pigments also decreased more than that of Nymphaea lotus. The soluble sugar content, SOD enzyme activity and CAT enzyme activity of Nymphaea lotus were higher than those of Nymphaea rubra. This indicated that there were significant differences in the cold sensitivity of the two varieties. GO enrichment and KEGG pathway analysis showed that many stress response genes and pathways were affected and enriched to varying degrees under the cold stress, especially plant hormone signal transduction, metabolic pathways and some transcription factor genes were from ZAT gene family or WKRY gene family. The key transcription factor ZAT12 protein in the cold stress response process has a C2H2 conserved domain, and the protein is localized in the nucleus. Under the cold stress, overexpression of the NlZAT12 gene in Arabidopsis thaliana increased the expression of some cold-responsive protein genes. The content of reactive oxygen species and MDA in transgenic Arabidopsis thaliana was lower, and the content of soluble sugar was higher, indicating that overexpression of NlZAT12 can improve the cold tolerance of Arabidopsis thaliana. CONCLUSION: We demonstrate that ethylene signalling and reactive oxygen species signalling play critical roles in the response of the two cultivars to cold stress. The key gene NlZAT12 for improving cold tolerance was identified. Our study provides a theoretical basis for revealing the molecular mechanism of tropical water lily in response to cold stress.

Ultrafine Titanium Monoxide (TiO1+x) Nanorods for Enhanced Sonodynamic Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) that enables noninvasive treatment of large internal tumors has attracted widespread interest. For improvement in the therapeutic responses to SDT, more effective and stable sonosensitizers are still required. Herein, ultrafine titanium monoxide nanorods (TiO1+x NRs) with greatly improved sono-sensitization and Fenton-like catalytic activity were fabricated and used for enhanced SDT. TiO1+x NRs with an ultrafine rodlike structure were successfully prepared and then modified with polyethylene glycol (PEG). Compared to the conventional sonosensitizer, TiO2 nanoparticles, the PEG-TiO1+x NRs resulted in much more efficient US-induced generation of reactive oxygen species (ROS) because of the oxygen-deficient structure of TiO1+x NR, which predominantly serves as the charge trap to limit the recombination of US-triggered electron-hole pairs. Interestingly, PEG-TiO1+x NRs also exhibit horseradish-peroxidase-like nanozyme activity and can produce hydroxyl radicals (•OH) from endogenous H2O2 in the tumor to enable chemodynamic therapy (CDT). Because of their efficient passive retention in tumors post intravenous injection, PEG-TiO1+x NRs can be used as a sonosensitizer and CDT agent for highly effective tumor ablation under US treatment. In addition, no significant long-term toxicity of PEG-TiO1+x NRs was found for the treated mice. This work highlights a new type of titanium-based nanostructure with great performance for tumor SDT.

H2O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay.

Abnormal H2O2 levels are closely related to many diseases, including inflammation and cancers. Herein, we simultaneously load HRP and its substrate, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), into liposomal nanoparticles, obtaining a Lipo@HRP&ABTS optical nanoprobe for in vivo H2O2-responsive chromogenic assay with great specificity and sensitivity. In the presence of H2O2, colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared (NIR) absorbance, enabling photoacoustic detection of H2O2 down to submicromolar concentrations. Using Lipo@HRP&ABTS as an H2O2-responsive nanoprobe, we could accurately detect the inflammation processes induced by LPS or bacterial infection in which H2O2 is generated. Meanwhile, upon systemic administration of this nanoprobe we realize in vivo photoacoustic imaging of small s.c. tumors (∼2 mm in size) as well as orthotopic brain gliomas, by detecting H2O2 produced by tumor cells. Interestingly, local injection of Lipo@HRP&ABTS further enables differentiation of metastatic lymph nodes from those nonmetastatic ones, based on their difference in H2O2 contents. Moreover, using the H2O2-dependent strong NIR absorbance of Lipo@HRP&ABTS, tumor-specific photothermal therapy is also achieved. This work thus develops a sensitive H2O2-responsive optical nanoprobe useful not only for in vivo detection of inflammation but also for tumor-specific theranostic applications.

Cancer-associated fibroblast-derived exosomal microRNA-98-5p promotes cisplatin resistance in ovarian cancer by targeting CDKN1A.

BACKGROUND: Ovarian cancer (OC) is a gynecological malignancy with a high mortality. Cisplatin-based treatment is the typical treatment regimen for OC patients; however, it may cause unfavorable resistance. The current study intends to explore the function of cancer-associated fibroblast (CAF)-derived exosomal microRNA-98-5p (miR-98-5p) in cisplatin resistance in OC, and the participation of CDKN1A. METHODS: Bioinformatics analysis was employed in order to obtain cisplatin resistance-related differential genes in OC as well as possible upstream regulatory miRs. After gain- and loss-of-function assays in OC cells, RT-qPCR and western blot analysis were employed to measure CDKN1A and miR-98-5p expression. Dual luciferase reporter assay was applied to verify the targeting relationship between miR-98-5p and CDKN1A. CAFs were treated with miR-98-5p inhibitor, and then exosomes were isolated and co-cultured with OC cells. CCK-8, colony formation and flow cytometry assays were conducted to assess cell proliferation, cell colony formation, cell cycle distribution and cell apoptosis, respectively. At last, xenograft tumor in nude mice was carried out to test whether exosomal miR-98-5p could affect cisplatin resistance in OC in vivo. RESULTS: CDKN1A was highly expressed in cisplatin-sensitive OC cell lines, and silencing CDKN1A significantly promoted proliferation and cell cycle entry but decreased apoptosis in cisplatin-sensitive OC cells. miR-98-5p targeted CDKN1A to inhibit CDKN1A expression. CAF-derived exosomal miR-98-5p increased OC cell proliferation and cell cycle entry, but suppressed cell apoptosis. Furthermore, exosomal miR-98-5p promoted cisplatin resistance and downregulated CDKN1A in nude mice. CONCLUSION: Collectively, CAF-derived exosomes carrying overexpressed miR-98-5p promote cisplatin resistance in OC by downregulating CDKN1A.

Tumor-pH-Responsive Dissociable Albumin-Tamoxifen Nanocomplexes Enabling Efficient Tumor Penetration and Hypoxia Relief for Enhanced Cancer Photodynamic Therapy.

Despite the promises of applying nano-photosensitizers (nano-PSs) for photodynamic therapy (PDT) against cancer, severe tumor hypoxia and limited tumor penetration of nano-PSs would lead to nonoptimized therapeutic outcomes of PDT. Therefore, herein a biocompatible nano-PS is prepared by using tamoxifen (TAM), an anti-estrogen compound, to induce self-assembly of chlorin e6 (Ce6) modified human serum albumin (HSA). The formed HSA-Ce6/TAM nanocomplexes, which are stable under neutral pH with a diameter of ≈130 nm, would be dissociated into individual HSA-Ce6 and TAM molecules under the acidic tumor microenvironment, owing to the pH responsive transition of TAM from hydrophobic to hydrophilic. Upon systemic administration, such HSA-Ce6/TAM nanoparticles exhibit prolonged blood circulation and high accumulation in the tumor, where it would undergo rapid pH responsive dissociation to enable obviously enhanced intratumoral penetration of HSA-Ce6. Furthermore, utilizing the ability of TAM in reducing the oxygen consumption of cancer cells, it is found that HSA-Ce6/TAM after systemic administration could efficiently attenuate the tumor hypoxia status. Those effects acting together lead to remarkably enhanced PDT treatment. This work presents a rather simple approach to fabricate smart nano-PSs with multiple functions integrated into a single system via self-assembly of all-biocompatible components, promising for the next generation cancer PDT.

Evidence that growth hormone can improve mitochondrial function in oocytes from aged mice.

Decline in successful conception decreases more rapidly after 38 years of age owing to follicular depletion and decreased oocyte quality. However, limited information is available regarding the underlying mechanism and the useful treatment. This study aimed to evaluate the effects of growth hormone supplementation on oocyte maturation in vivo in aged and young mice and to determine its effect on mitochondrial function. The influence of three different doses of recombinant human growth hormone (rhGH) (0.4, 0.8 and 1.6 mg/kg/day) for 8 weeks before ovarian stimulation was analyzed. Superovulated oocytes were released from the oviduct of 12-week-old and 40-week-old female C57BL/6J mice 14-16 h after administration of human chorionic gonadotropin. Ovarian follicle and morphological analysis and oocyte maturation parameters were then evaluated. This study is the first, to our knowledge, to report that medium- and high-dose rhGH significantly increases antral follicles in aged mice but anti-Müllerian hormone (AMH) levels. Furthermore, derived oocytes, MII-stage oocyte rate, ATP levels, mitochondrial membrane potential and frequencies of homogeneous mitochondrial distribution increased. In contrast, in both aged and young mice, the mtDNA copy numbers per oocyte were similar before rhGH administration, and upon saline administration, they did not differ significantly. We conclude that medium-dose rhGH supplementation before standard ovarian stimulation regimens improves oocyte quality in aged mice, probably by enhancing mitochondrial functionality.

Corrective effects of maternal extreme flexure and hip abduction combined with contralateral side-lying on persistent foetal occipito-posterior position.

AIMS: To observe the corrective effects of maternal extreme flexure and hip abduction combined with contralateral side-lying on persistent foetal occipito-posterior position. BACKGROUND: Digital rotation and other methods are used for correction of a persistent foetal occipito-posterior position. However, digital rotation readily causes damage to mother and foetus, and the correction rates of other methods are low. DESIGN: In this observational study, pregnant women were randomly divided into 2 groups according to different postures and their outcomes were compared. METHODS: A total of 238 women with persistent foetal occipito-posterior position gave birth in our hospital between January 2015 and June 2017. Of these 238 cases, 12 women declined to participate. The 226 pregnant women were divided into study group (maternal extreme flexure and hip abduction combined with contralateral side-lying, n = 114) and control group (contralateral side-lying alone, n = 112). RESULTS: The correction and spontaneous labour rates were higher in the study group than in the control group (P < .05). The duration between initial and successful correction and birth process were shorter in the study group than in the control group (P < .05). CONCLUSION: Maternal extreme flexure and hip abduction combined with contralateral side-lying has better correction effect on persistent foetal occipito-posterior position.

An Analysis of Prognostic Factors in Patients with Ovarian Malignant Germ Cell Tumors Who Are Treated with Fertility-Preserving Surgery.

BACKGROUND/AIMS: To analyze the clinicopathological factors that affect the prognosis and fertility of patients with malignant ovarian germ cell tumors (MOGCTs). METHODS: The medical records and follow-up data of 106 patients with MOGCTs who were treated at The Affiliated Tumor Hospital of Guangxi Medical University between January 1986 and December 2010 were enrolled in this study. A Kaplan-Meier analysis was used to analyze the survival curves. The different prognoses among the various clinicopathological factors were evaluated using a univariate analysis and a log-rank test. The multivariate analysis was performed using the Cox proportional hazard regression method. A logistic regression analysis was used to evaluate the influence of different factors on the prognoses and fertility. RESULTS: The median age at primary treatment was 22 years (range: 9-61years). A total of 59 patients received fertility-preserving surgery, 45 received radical surgery and 94 received postoperative adjuvant chemotherapy. The median follow-up time was 56.5 months (range: 2-309 months). A total of 11 patients experienced a recurrence, and 23 patients died from their cancer. Of the 47 patients who are alive without tumor, 45 have normal menstruation. Of the 39 patients who wished to become pregnant, 31 patients had 33 successful pregnancies that resulted in 33 live births. No statistically significant difference (p > 0.05) was observed with respect to the progression-free survival (PFS; 67.6 vs. 63.3%), the overall survival (OS; 70 vs. 64.1%) and the mortality rate (15.3 vs. 31.3%) between patients who received fertility-preserving surgery and those who received radical surgery. The univariate analysis showed that the pathological types, postoperative residual tumor size, lymph node resection, and omental resection were associated with OS (p < 0.1), whereas postoperative residual tumor size, number of chemotherapy cycles, lymph node resection, and omental resection were associated with PFS (p < 0.1). The multivariate analysis showed that only the postoperative residual tumor size was an independent prognostic factor of OS, whereas the postoperative residual tumor size, number of chemotherapy cycles and lymph node resection were independent prognostic factors of PFS. No statistically significant difference (p > 0.05) was observed with respect to the OS, PFS and fertility between patients who received fertility-preserving surgery and those who were treated with or without comprehensive surgical staging. CONCLUSION: MOGCTs can achieve a good prognosis after surgery and chemotherapy. Postoperative residual tumor size was an independent prognostic factor of PFS and OS. Moreover, comprehensive surgical staging cannot improve the prognosis. Fertility-preserving surgery plus adjuvant chemotherapy appeared to have little or no effect on prognosis and fertility.

Rhizosphere metabolic cross-talk from plant-soil-microbe tapping into agricultural sustainability: Current advance and perspectives.

Rhizosphere interactions from plant-soil-microbiome occur dynamically all the time in the "black microzone" underground, where we can't see intuitively. Rhizosphere metabolites including root exudates and microbial metabolites act as various chemical signalings involving in rhizosphere interactions, and play vital roles on plant growth, development, disease suppression and resistance to stress conditions as well as proper soil health. Although rhizosphere metabolites are a mixture from plant roots and soil microbes, they often are discussed alone. As a rapid appearance of various omics platforms and analytical methods, it offers possibilities and opportunities for exploring rhizosphere interactions in unprecedented breadth and depth. However, our comprehensive understanding about the fine-tuning mechanisms of rhizosphere interactions mediated by these chemical compounds still remain clear. Thus, this review summarizes recent advances systemically including the features of rhizosphere metabolites and their effects on rhizosphere ecosystem, and looks forward to the future research perspectives, which contributes to facilitating better understanding of biochemical communications belowground and helping identify novel rhizosphere metabolites. We also address challenges for promoting the understanding about the roles of rhizosphere metabolites in different environmental stresses.

Tumor Microenvironment Modulating CaCO3 -Based Colloidosomal Microreactors Can Generally Reinforce Cancer Immunotherapy.

Tumor hypoxia and acidity, two general features of solid tumors, are known to have negative effect on cancer immunotherapy by directly causing dysfunction of effector immune cells and promoting suppressive immune cells inside tumors. Herein, a multifunctional colloidosomal microreactor is constructed by encapsulating catalase within calcium carbonate (CaCO3 ) nanoparticle-assembled colloidosomes (abbreviated as CaP CSs) via the classic double emulsion method. The yielded CCaP CSs exhibit well-retained proton-scavenging and hydrogen peroxide decomposition performances and can thus neutralize tumor acidity, attenuate tumor hypoxia, and suppress lactate production upon intratumoral administration. Consequently, CCaP CSs treatment can activate potent antitumor immunity and thus significantly enhance the therapeutic potency of coloaded anti-programmed death-1 (anti-PD-1) antibodies in both murine subcutaneous CT26 and orthotopic 4T1 tumor xenografts. In addition, such CCaP CSs treatment also markedly reinforces the therapeutic potency of epidermal growth factor receptor expressing chimeric antigen receptor T (EGFR-CAR-T) cells toward a human triple-negative breast cancer xenograft by promoting their tumor infiltration and effector cytokine secretion. Therefore, this study highlights that chemical modulation of tumor acidity and hypoxia can collectively reverse tumor immunosuppression and thus significantly potentiate both immune checkpoint blockade and CAR-T cell immunotherapies toward solid tumors.

Self-fueling ferroptosis-inducing microreactors based on pH-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy.

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma (HCC) via transarterial chemoembolization (TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion (LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase (LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE (LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids (PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

Identification and Association of SNPs in TBC1D1 Gene with Growth Traits in Two Rabbit Breeds.

The TBC1D1 plays a key role in body energy homeostasis by regulating the insulin-stimulated glucose uptake in skeletal muscle. The present study aimed to identify the association between genetic polymorphisms of TBC1D1 and body weight (BW) in rabbits. Among the total of 12 SNPs detected in all 20 exons, only one SNP was non-synonymous (c.214G>A. p.G72R) located in exon 1. c.214G>A was subsequently genotyped among 491 individuals from two rabbit breeds by the high-resolution melting method. Allele A was the predominant allele with frequencies of 0.7780 and 0.6678 in European white rabbit (EWR, n = 205) and New Zealand White rabbit (NZW, n = 286), respectively. The moderate polymorphism information content (0.250.05). Our results implied that the c.214G>A of TBC1D1 gene might be one of the candidate loci affecting the trait of 35 d BW in the rabbit.

Removal of virus aerosols by the combination of filtration and UV-C irradiation.

The COVID-19 pandemic remains ever prevalent and afflicting-partially because one of its transmission pathways is aerosol. With the widely used central air conditioning systems worldwide, indoor virus aerosols can rapidly migrate, thus resulting in rapid infection transmission. It is therefore important to install microbial aerosol treatment units in the air conditioning systems, and we herein investigated the possibility of combining such filtration with UV irradiation to address virus aerosols. Results showed that the removal efficiency of filtration towards f2 and MS2 phages depended on the type of commercial filter material and the filtration speed, with an optimal velocity of 5 cm/s for virus removal. Additionally, it was found that UV irradiation had a significant effect on inactivating viruses enriched on the surfaces of filter materials; MS2 phages had greater resistance to UV-C irradiation than f2 phages. The optimal inactivation time for UV-C irradiation was 30 min, with higher irradiation times presenting no substantial increase in inactivation rate. Moreover, excessive virus enrichment on the filters decreased the inactivation effect. Timely inactivation is therefore recommended. In general, the combined system involving filtration with UV-C irradiation demonstrated a significant removal effect on virus aerosols. Moreover, the system is simple and economical, making it convenient for widespread implementation in air-conditioning systems.

Disulfiram loaded calcium phosphate nanoparticles for enhanced cancer immunotherapy.

Considering the huge cost and long test periods required for new drug development, repurposing drugs that have already been applied in the clinic as new cancer treatment candidates represents an attractive alternative. Disulfiram (DSF) was originally used to treat alcoholism and has proven to have anticancer effects with the coadministration of copper ions (Cu2+). However, the limited water-solubility of DSF and systemic toxicity induced by exogenous Cu2+ hinder its practical application. Herein, we constructed pH-responsive lipid-coated calcium phosphate nanoparticles (LCP NPs) co-loaded with Cu2+ and DSF. After intravenous injection, those nanoparticles with long blood half-life preferentially accumulate in tumors, followed by the degradation of nanoparticles in response to the acidic tumor microenvironment, subsequently releasing Cu2+ and DSF to generate cytotoxic metabolite DTC-Copper complex, bis(diethyldithiocarbamate)-copper (CuET) for tumor treatment. In addition to direct cytotoxicity, the active metabolite CuET could effectively induce immunogenic cell death (ICD) of cancer cells to regulate the immunosuppressive tumor microenvironment, contributing to enhanced immune checkpoint blockade (ICB) therapy in triggering systemic immune responses. This work thus demonstrates the great promises of repurposing the old drug DSF as a new ICD inducer with nano-formulation, to achieve improved synergetic tumor-responsive therapy with low side effects.

Identification of Ferroptosis-Related Gene Prognostic Signature and HSF1 for Reversing Doxorubicin and Gemcitabine Resistance in Uterine Carcinosarcoma.

PURPOSE: Iron metabolism and ferroptosis play crucial roles in the pathogenesis of cancer. In this study, we aim to study the role of ferroptosis-related genes (FRGs) in uterine carcinosarcoma (UCS) and identify potential target for UCS. METHODS: Prognostic differentially expressed FRGs were identified of in the TCGA cohort. Integrated analysis, cox regression, and the least absolute shrinkage and selection operator (LASSO) methods of FRGs were performed to construct a multigene signature prognostic model. Moreover, a dataset from Gene Expression Omnibus (GEO) served as an external validation. HSF1 was knockdown in MES-SA and FU-MMT-1 cells, and cell viability, lipid ROS, and intracellular iron level were detected when combined with doxorubicin or gemcitabine. RESULT: Five FRGs were selected to construct a prognostic model of UCS. The group with high-risk signature score exhibited obviously lower overall survival (OS) than the group with low risk signature score in both TCGA and validated GEO cohorts. Multivariate Cox regression analysis further indicated that the risk score was an independent factor for the prognosis of UCS patients. The high-risk group of UCS has a higher sensitivity in the treatment of doxorubicin and gemcitabine. Knocking down of HSF1 in MES-SA and FU-MMT-1 cells was more sensitive to doxorubicin and gemcitabine via increasing ferroptosis. CONCLUSIONS: The five FRGs risk signature prognostic model having a superior and drug sensitivity predictive performance for OS in UCS, and HSF1 is a potential marker sensitive to doxorubicin and gemcitabine in UCS patients.

Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy.

Relieving tumor hypoxia has recently been found to be a promising approach to reverse tumor immunosuppression and thus enhance the treatment outcomes of diverse cancer treatments. Herein, we prepared a type of fluorinated covalent conjugate polymers (COPs) with sonosensitizer meso-5, 10, 15, 20-tetra (4-hydroxylphenyl) porphyrin (THPP) and perfluorosebacic acid (PFSEA) as cross-linkers, yielding THPPpf-COPs with efficient sonodynamic efficacy and loading capacity towards perfluoro-15-crown-5-ether (PFCE), a model perfluorocarbon molecule. Upon intratumoral injection, such PFCE@THPPpf-COPs could not only attenuate tumor hypoxia, but also exhibit the most effective suppression effect on tumor growth in the presence of ultrasound exposure by inducing immunogenic cell death of cancer cells. Furthermore, we found that the sonodynamic therapy of PFCE@THPPpf-COPs together with anti-CD47 immunotherapy would synergistically suppress tumor growth by increasing the tumor-infiltrating frequencies of phagocytic M1 macrophages and cytotoxic CD3+CD8+ T cells, while reducing the frequency of immunosuppressive regulatory T cells. Moreover, such combination treatment could also elicit potent protective memory antitumor immunity to prevent tumor challenge. Therefore, this work presents PFCE@THPPpf-COPs are a type of multifunctional nano-sonosensitizers potent in removing negative impacts of inherent tumor hypoxia and immunosuppression, and suppressing tumor growth and tumor recurrence by priming host's antitumor immunity, particularly in synergizing with anti-CD47 immunotherapy.

Engineering bioluminescent bacteria to boost photodynamic therapy and systemic anti-tumor immunity for synergistic cancer treatment.

The limited penetration depth of external excitation light would remarkably impair the therapeutic efficacy of photodynamic therapy (PDT) and its clinical utilization. Herein, we engineered bioluminescent bacteria by transforming attenuated Salmonella typhimurium strain ΔppGpp (S.T.ΔppGpp) with firefly-luciferase-expressing plasmid (Luc-S.T.ΔppGpp) as an internal light source to evenly illuminate whole tumors. Upon being fixed inside tumors with in-situ formed hydrogel, the colonized Luc-S.T.ΔppGpp together with D-luciferin could continuously generate light to excite photosensitizer chlorin e6 (Ce6), leading to effective suppression of different types of tumors including opaque melanoma and large rabbit tumors. Such bioluminescence-triggered PDT presented significant advantages over conventional PDT excited with an external 660-nm light, which at a much high light energy could only slightly retard the growth of small subcutaneous tumors. Furthermore, we uncovered that Luc-S.T.ΔppGpp boosted PDT could also elicit potent antitumor immunity post the treatment to inhibit tumor metastasis and prevent tumor challenge. Therefore, this work highlights that such bioluminescent bacteria boosted PDT is a general and highly effective therapeutic approach toward diverse cancers with varying light-absorbing capacities and tumor sizes, promising for potential clinical translation because of their acceptable safety profiles.

Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment.

Microwave ablation (MWA) as a local tumor ablation strategy suffers from posttreatment tumor recurrence. Development of adjuvant biomaterials to potentiate MWA is therefore of practical significance. Here, the high concentration of Ca2+ fixed by alginate as Ca2+-surplus alginate hydrogel shows enhanced heating efficiency and restricted heating zone under microwave exposure. The high concentration of extracellular Ca2+ synergizes with mild hyperthermia to induce immunogenic cell death by disrupting intracellular Ca2+ homeostasis. Resultantly, Ca2+-surplus alginate hydrogel plus MWA can ablate different tumors on both mice and rabbits at reduced operation powers. This treatment can also elicit antitumor immunity, especially if synergized with Mn2+, an activator of the stimulation of interferon genes pathway, to suppress the growth of both untreated distant tumors and rechallenged tumors. This work highlights that in situ-formed metallo-alginate hydrogel could act as microwave-susceptible and immunostimulatory biomaterial to reinforce the MWA therapy, promising for clinical translation.