Search

Abstract The objective of this prospective study was to assess the efficacy of Hiporfin-photodynamic therapy (PDT) int the treatment of young women diagnosed with high-grade squamous intraepithelial lesions (HSIL) of the endocervical canal. This study included 14 patients aged 30 ± 4.2 years (range 21–37) with HSIL of the cervical canal, treated at our hospital from August 2021 to June 2023. Hiporfin (2 mg/kg) was administered intravenously and laser irradiation with a 630 nm wavelength was performed on the cervical canal and cervical surface 48–72 h later. All patients had been observed for at least 12 months. 64.3% (9/14) were nulliparous. The complete response (CR) rate of cervical canal involvement was 100.0% (14/14) at 3–6 months. Pre-PDT, all patients (14/14) tested positive for high-risk human papilloma virus (HR-HPV). The HPV eradication rate was 64.3% (9/14) at 3–6 months and 85.7% (12/14) at 12 months. No serious adverse effects were observed in patients during or after PDT. No recurrence was noted during the long-time follow-up. 6 patients who planned to get pregnant achieved 6 pregnancies including 1 spontaneous abortion, 2 term pregnancies, and 3 ongoing pregnancies. No fetal loss occurred due to cervical incompetence. Hiporfin-PDT may be a promising, fertility-preserving treatment for HSIL of the endocervical canal in young women.

Abstract The study aimed to compare the effectiveness between Hiporfin-photodynamic therapy (PDT) and loop electrosurgical excision procedure (LEEP) in treating cervical high-grade squamous intraepithelial lesion (HSIL). We conducted a retrospective analysis of 104 women diagnosed with cervical HSIL at our hospital from April 2019 to July 2023. With 1:1 matched case-control, 52 cases received Hiporfin-PDT and 52 cases underwent LEEP. All PDT-treated cases received Hiporfin (2 mg/kg) I.V. and a diode laser at a wavelength of 630-nm. T-test, Chi-square test, Fisher’s exact test, and Yates’s correction for continuity were conducted for statistical. A P value

Abstract Uterine arteriovenous malformation (UAM) is a rare medical condition. Even though UAM can cause abnormal and life-threatening uterine hemorrhage, there is no consensus on the clinical guideline on its treatments, most likely due to its low incidence, unknown etiology, and distinct fertility demands by different patients. Here, we present one elderly woman with uncommon UAM. We first discuss our experience regarding the diagnoses and treatments of UAM and then propose a hypothesis for the pathogenesis of UAM.

This study aimed to investigate the effects of nano-selenium (nano-se) as a dietary supplement on Tibetan naked carp (Gymnocypris przewalskii) and six separate groups were conducted (0 mg/kg, NSEC; 2 mg/kg, NSE2; 4 mg/kg, NSE4; 7 mg/kg, NSE7; 9 mg/kg, NSE9; and 11 mg/kg, NSE11). The growth performance, hemato-biochemical activity, antioxidant activity, immune indices, and intestinal microbiota were subsequently measured at the end of the feeding experiment. The results showed that the hepatosomatic index, viscerosomatic index and condition factor were significantly greater in the NSE4 group (P < 0.05). The NSE4 group presented the highest specific growth rate and weight gain rate, whereas the NSE11 group presented the lowest rates. The survival rate was greater in the NSE2, NSE4, and NSE9 groups, whereas it was lowest in the NSE11 group. The contents of TP and TG and the activities of T-AOC, GSH-Px, T-SOD, CAT and GR first increased but then decreased with increasing dietary selenium content. Compared with the other groups, the NSE4 group presented comparatively lower levels of proinflammatory factors such as IL-1β, IL-6, and TNF-α, but higher amounts of lysozyme LZM and immunoglobulin IgM. The NSE4 and NSE2 groups presented considerably increased levels of anti-inflammatory factors (IL-10 and TGF-β) (P < 0.05). Dietary supplementation with an appropriate amount of nano-se can improve liver vacuolationand hepatocyte swelling in G. przewalskii, but excessive nano-se could cause liver damage. In addition, the results of intestinal microbiota detection revealed that dietary nano-se could improve the diversity of the intestinal microbiota and increase the abundance of beneficial bacteria in G. przewalskii. This research will enhance our understanding of the possible uses of nano-se and lay the groundwork for increasing the resource efficiency of G. przewalskii breeding and releasing.

Mesenchymal stem cells (MSCs) have attracted more and more attention because of their multidirectional differentiation potential, immune regulatory abilities and self-renewal capacity. In recent years, their use has become prominent in the domains of regenerative medicine and tissue engineering. MSCs have shown promise in therapeutic studies for a variety of diseases and have become a new source of innovative solutions for the treatment of some obstetric and gynecological diseases. This review systematically presents the latest research on the use of MSCs in the treatment of obstetrics- and gynecology-related diseases. Specifically, this review encompasses the latest findings related to the role of MSCs in premature ovarian failure, polycystic ovary syndrome, ovarian cancer, fallopian tube-related diseases, uterine adhesions, endometriosis, cesarean scar defects, postmenopausal osteoporosis, and pelvic floor dysfunction. The shortcomings and challenges of the future use of MSCs in disease treatment are also discussed, with the intent to motivate improvements in MSC applications in clinical therapy. It is believed that with further research, MSCs will play a more important role in the treatment of obstetrics- and gynecology-related diseases.

Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, a novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. Cu targets lipoylated enzymes in the tricarboxylic acid cycle and subsequently triggers the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, leading to the loss of Fe–S clusters and induction of heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer and uterine corpus endometrial carcinoma significantly impact women’s quality of life and even pose a threat to their lives. Excessive Cu can promote cancer progression by enhancing tumor growth, proliferation, angiogenesis and metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers in relation to cuproptosis. Therefore, this review discusses Cu homeostasis and cuproptosis while exploring the potential use of cuproptosis for prognosis prediction as well as its implications in the progression and treatment of gynecological cancers. Additionally, we explore the application of Cu ionophore therapy in treating gynecological malignancies.

Abstract There is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.

Triploid rainbow trout is a hypoxia-sensitive fish species, and is susceptible to death in summer with high water temperature induced acute hypoxia. The study was conducted to evaluate the effect of high protein diet and high carbohydrate diet on hypoxic tolerance of triploid rainbow trout. Two isolipidic and isoenergetic diets with low protein-high carbohydrate level (LPHC) and high protein-low carbohydrate level (HPLC) were specifically formulated. After the feeding trial with 80 days, two group fish were treated with acute hypoxic challenge. Plasma biochemical parameters, hepatic anti-stress, antioxidant and immune related genes expression, and hepatic glucose, lipid, protein and amino acid metabolism related genes expression were then analyzed. The results showed that compared with HPLC diet, LPHC diet could result in excessive plasma levels of alanine aminotransferase (ALT; 36.3 VS 14.0 U/L), aspartate aminotransferase (AST; 978 VS 366 U/L), alkaline phosphatase (ALP; 374 VS 204 U/L), creatine phosphokinase (CPK; 7538 VS 4937 U/L) and lactate dehydrogenase (LDH; 940 VS 451 U/L). In addition, HPLC diet could remodel metabolism of glucose, lipid and protein based on the mRNA expression levels of the genes regulating glycometabolism, lipometabolism, and protein and amino acids metabolism. HPLC diet also enhanced the mRNA expression levels of the genes regulating anti-stress (HSP70, HIF-1a and HIF-2a), antioxidant (Nrf2, SOD, CAT, GPx and HO-1) and immune (IFN-γ, IL-1β, TNF-α and IL-8). In total, LPHC diet could aggravate hypoxic stress of triploid rainbow trout, while HPLC diet could improve fish hypoxic tolerance.

Key Clinical Message We present a rare case of a female pelvic solitary fibrous tumor unsuccessfully resected using single‐port laparoscopy, requiring conversion to laparotomy. Although the resection was successful, the surgical approach could have been improved. For large tumors, minimally invasive results are possible with flexible choices of equipment and incision position.

Abstract Background Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis. Results The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%). Conclusions The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.

Given the shortage of cytologists, women in low-resource regions had inequitable access to cervical cytology which plays an pivotal role in cervical cancer screening. Emerging studies indicated the potential of AI-assisted system in promoting the implementation of cytology in resource-limited settings. However, there is a deficiency in evaluating the aid of AI in the improvement of cytologists’ work efficiency. This study aimed to evaluate the feasibility of AI in excluding cytology-negative slides and improve the efficiency of slide interpretation. Well-annotated slides were included to develop the classification model that was applied to classify slides in the validation group. Nearly 70% of validation slides were reported as negative by the AI system, and none of these slides were diagnosed as high-grade lesions by expert cytologists. With the aid of AI system, the average of interpretation time for each slide decreased from 3 minutes to 30 seconds. These findings suggested the potential of AI-assisted system in accelerating slide interpretation in the large-scale cervical cancer screening.

Nanomaterials with excellent optical, electric, magnetic, and other physicochemical properties, are generally used in photodynamic therapy, chemodynamic therapy, and photothermal therapy of cancer. To enhance nanomaterials’ superior physicochemical properties and improve cancer theranostic efficiency, various strategies have been proposed. Among them, the introduction of sulfur vacancy defects is a promising strategy for enhanced cancer theranostics. In this review, the formation and action mechanism of sulfur vacancy nanomaterials, as well as their application in cancer theranostics are first summarized. Then, the principle and application of various sulfur vacancy based-nanomaterials such as molybdenum, bismuth, zinc, copper, iron, ruthenium, silver, cobalt, cadmium, and polythionine in enhancing cancer therapy are highlighted. Finally, the future development prospect and current challenges of sulfur vacancy nanomaterials are also discussed. This review will help researchers quickly understand the information related to various sulfur vacancy-based nanomaterials in cancer therapy, promoting the further development of anti-cancer nanomedicine.

Neuropathic pain (NP) is known to be associated with abnormal changes in specific brain regions, but the complex neural network behind it is vast and complex and lacks a systematic summary. With the help of various animal models of NP, a literature search on NP brain regions and circuits revealed that the related brain nuclei included the periaqueductal gray (PAG), lateral habenula (LHb), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC); the related brain circuits included the PAG-LHb and mPFC-ACC. Moreover, acupuncture and injurious information can affect different brain regions and influence brain functions via multiple aspects to play an analgesic role and improve synaptic plasticity by regulating the morphology and structure of brain synapses and the expression of synapse-related proteins; maintain the balance of excitatory and inhibitory neurons by regulating the secretion of glutamate, γ-aminobutyric acid, 5-hydroxytryptamine, and other neurotransmitters and receptors in the brain tissues; inhibit the overactivation of glial cells and reduce the release of pro-inflammatory mediators such as interleukins to reduce neuroinflammation in brain regions; maintain homeostasis of glucose metabolism and regulate the metabolic connections in the brain; and play a role in analgesia through the mediation of signaling pathways and signal transduction molecules. These factors help to deepen the understanding of NP brain circuits and the brain mechanisms of acupuncture analgesia.

Abstract Surgical resection is a widely used method for the treatment of solid tumor cancers. However, the inhibition of tumor recurrence and metastasis are the main challenges of postoperative tumor therapy. Traditional intravenous or oral administration have poor chemotherapeutics bioavailability and undesirable systemic toxicity. Polymeric hydrogels with a three-dimensional network structure enable on-site delivery and controlled release of therapeutic drugs with reduced systemic toxicity and have been widely developed for postoperative adjuvant tumor therapy. Among them, because of the simple synthesis, good biocompatibility, biodegradability, injectability, and multifunctionality, iron-based hydrogels have received extensive attention. This review has summarized the general synthesis methods and construction principles of iron-based hydrogels, highlighted the latest progress of iron-based hydrogels in postoperative tumor therapy, including chemotherapy, photothermal therapy, photodynamic therapy, chemo-dynamic therapy, and magnetothermal-chemical combined therapy, etc. In addition, the challenges towards clinical application of iron-based hydrogels have also been discussed. This review is expected to show researchers broad perspectives of novel postoperative tumor therapy strategy and provide new ideas in the design and application of novel iron-based hydrogels to advance this sub field in cancer nanomedicine.

The research is aimed at investigating the effects of dietary protein and lipid levels on adult triploid rainbow trout growth performance, feed utilization, digestive and metabolic enzyme activities, antioxidative capacity, and fillet quality. Nine diets containing three dietary protein levels (DP) (300, 350, and 400 g kg-1) and three dietary lipid levels (DL) (200, 250, and 300 g kg-1) were prepared using a 3×3 factorial design. In freshwater cages, 13,500 adult female triploid rainbow trout (3.2±0.1 kg) were cultured for 77 days. Triplicate cages (500 fish per cage) were used as repetitions of each experimental diet. The findings revealed that as DP increased to 400 g kg-1 and DL raised to 300 g kg-1, the weight gain ratio (WGR) elevated significantly (P

The reserves of nitrate (NO3-) mineral resources in the Turpan-Hami Basin in Xinjiang rank second after those in the Atacama Desert in Chile, South America. Considerable attention has been devoted to nitrogen (N) sources of NO3- deposits in recent years due to the increase in demand for NO3- fertilizers in agriculture and chemical industries. However, although the potassium nitrate (KNO3) deposits in the Uyunbulak salt lake in the Kumish basin, Xinjiang, China, have received increasing attention from numerous researchers in recent years, they all focused on the study of nitrate sources and agreed that the nitrate source in the Kumish basin is mainly atmospheric sedimentation. Studies on their water sources are scarce; for salt lake nitrate deposits, water supply also plays a crucial role in the genesis of the deposit. As a sensitive indicator, a boron isotope is often used to indicate water bodies from different sources. However, the presence of NO3- ions in water will interfere with the determination of boron isotopes, so the research on boron isotopes in nitrate salt lakes has been hindered. In this study, the three-step ion exchange method published by Ma et al. (2020) was used to eliminate the influence of NO3- ions in water on boron isotope determination, so as to reveal the water supply of Uyunbulak Salt Lake in Kumish basin by using boron isotopes which are more sensitive to water types. In this study, ice and snow meltwater, fissure water, groundwater, and surface water samples were collected from the Kumish basin and analyzed for the determination of boron (B) isotopic and hydrochemical compositions during the migration process of water bodies to reveal the recharge relationship between the water bodies from the northwestern margin of the basin and the study area. The obtained hydrochemical composition results showed a gradual increase in the salinity of the water body from 556 to 7372 mg/L from the northwestern to the southeastern parts of the basin, resulting in a gradual change in the hydrochemical facies type of Uyunbulak salt lake to NaCl. This finding suggested that the water body migrates from the northwestern to southeastern parts of the basin. The results of B isotope composition indicated two types of water bodies from different sources, namely, the ice and snow meltwater of the Southern part of the Tianshan Mountains and groundwater of the basin, exhibiting B isotope composition ranges of 26.66–27.26‰ and 12.75–15.19‰, respectively. These two types of water bodies are mixed at the Uzong spring (Q1). The ice and snow meltwater in the mixed water accounted for 46%, while the groundwater accounted for 54%. The mixed water continues to recharge the Uyunbulak Salt Lake in the southeastern part of the basin.

ObjectiveTo validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay.MethodsThe analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade.ResultsWe included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = −0.641, P < 0.001; r 12−HPVpool = −0.343, P = 0.109; In CIN2+, r HPV16 = −0.754, P < 0.001; r 12−HPVpool = −0.429, P < 0.001).ConclusionThe CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

Abstract Background The immune mechanism was shown to be involved in the development of adenomyosis. The aim of the current study was to evaluate the expression of the immune checkpoints B7-H2, B7-H3, B7-H4 and PD-L2 in adenomyosis and to explore the effect of mifepristone on the expression of these immune checkpoints. Methods The expression of B7-H2, B7-H3, B7-H4 and PD-L2 in normal endometria and adenomyosis patient samples treated with or without mifepristone was determined by immunohistochemistry analysis. Results In adenomyosis patient samples, the expression of B7-H2, B7-H3 and B7-H4 was increased in the eutopic and ectopic endometria compared with normal endometria, both in the proliferative and secretory phases. Moreover, the expression of B7-H2 and B7-H3 was higher in adenomyotic lesions than in the corresponding eutopic endometria, both in the proliferative and secretory phases. The expression of PD-L2 was higher in adenomyotic lesions than in normal endometria in both the proliferative and secretory phases. In the secretory phase but not the proliferative phase, the expression of B7-H4 and PD-L2 in adenomyotic lesions was significantly higher than that in the corresponding eutopic endometria. In normal endometria and eutopic endometria, the expression of B7-H4 was elevated in the proliferative phase compared with that in the secretory phase, while in the ectopic endometria, B7-H4 expression was decreased in the proliferative phase compared with the secretory phase. In addition, the expression of B7-H2, B7-H3, B7-H4 and PD-L2 was significantly decreased in adenomyosis tissues after treatment with mifepristone. Conclusions The expression of the immune checkpoint proteins B7-H2, B7-H3, B7-H4 and PD-L2 is upregulated in adenomyosis tissues and is downregulated with mifepristone treatment. The data suggest that B7 immunomodulatory molecules are involved in the pathophysiology of adenomyosis.

Background The velvet antler is a complex mammalian bone organ with unique biological characteristics, such as regeneration. The rapid growth stage (RGS) is a special period in the regeneration process of velvet antler. Methods To elucidate the functions of microRNAs (miRNAs) at the RGS of antler development in Gansu red deer (Cervus elaphus kansuensis), we used RNA sequencing (RNA-seq) to analyze miRNA expression profiles in cartilage tissues of deer antler tips at three different growth stages. Results The RNA-seq results revealed 1,073 known and 204 novel miRNAs, including 1,207, 1,242, and 1,204 from 30-, 60-, and 90-d antler cartilage tissues, respectively. To identify key miRNAs controlling rapid antler growth, we predicted target genes of screened 25 differentially expressed miRNAs (DEMs) and specifically expressed miRNAs (SEMs) in 60 d and annotated their functions. The KEGG results revealed that target genes of 25 DEMs and 30 SEMs were highly classified in the “Metabolic pathways”, “Pathways in cancer”, “Proteoglycans in cancer” and “PI3K-Akt signaling pathway”. In addition, a novel miRNA (CM008039.1_315920), highly enriched in “NF-kappa B signaling pathway”, may need further study. Conclusions The miRNAs identified in our study are potentially important in rapid antler growth. Our findings provide new insights to help elucidate the miRNA-mediated regulatory mechanisms involved during velvet antler development in C. elaphus kansuensis.

Background The degradation of alpine meadows has induced substantial losses of soil organic carbon (SOC) on the Tibetan Plateau. A commonly-used method for rehabilitating degraded alpine meadows in this region is establishing cultivated grasslands through sowing seed mixtures, but its impact on the biochemical stability of SOC has remained inadequately explored. Methods In this study, a total of 20 composited 0-20 cm soil samples were collected from a heavily degraded alpine meadow (DM) and three adjacent cultivated grasslands established for 3 years (CG3), 12 years (CG12), and 17 years (CG17) on the eastern Tibetan Plateau, and the SOC pool was separated into labile C pool I (LOC I), labile C pool II (LOC II), and recalcitrant C pool (ROC) in order to investigate changes in contents of SOC fractions that have different biochemical stabilities after the establishment of cultivated grassland. Results Although the establishment of cultivated grasslands led to increases in soil total organic C content, the increase was only significant in samples with 17 years of cultivation. We found that the contents of the three SOC fractions were higher at CG3 and CG12 compared with those in the DM, and the differences were only significant for soil LOC II. By comparison, 17 years of cultivation led to significant increases in all of the SOC fraction contents. The results implied that different cultivation years had distinct impacts on SOC fractions in cultivated grasslands, and longer cultivation years contributed to accumulated soil ROC. The recalcitrance index of SOC in the DM was higher than that at CG3 and CG12, but lower than that at CG17. This was possibly due to the generally low litter quality of cultivated grasslands, which led to a slow release of complex compounds to soils. Moreover, it was observed that soil C:N ratio was a potential indicator of SOC biochemical stability because of their close correlation. Conclusions Our findings suggest that the long-term establishment of cultivated grasslands on DM is a promising solution to recovering both the quantity and stability of SOC on the Tibetan Plateau.

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SIL-positive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection.

Abstract The mortality rate of ovarian cancer (OC) remains the highest among all gynecological malignancies. Platinum-based chemotherapies are effective in treating most OC cases. However, chemoresistance is still a major challenge for successful OC treatments. Emerging evidence has highlighted that the modulation of the tumor immune microenvironment is involved in chemoresistance, but the mechanism remains unclear. This study aimed to investigate whether resistance to cisplatin (CDDP), the standard treatment for OC, is due to the remodeling of the tumor immune microenvironment by the transcription factor EB (TFEB). We hypothesized that TFEB is not essential for tumor survival but is associated with CDDP resistance. We collected 20 tissue samples of OC patients who had not undergone chemotherapy or radiotherapy prior to surgery. We cultured OC cell lines and performed cell transfection and assays as well as analytical, fluorescence microscopy, and immunohistochemical techniques to explore a novel function of TFEB in remodeling the tumor immune microenvironment in OC. We found a positive correlation between TFEB and programmed cell death-ligand 1 (PD-L1), PD-L2, and HLA-A expression in OC cells and tissues. We also found that CDDP treatment induced TFEB nuclear translocation, thus increasing PD-L1 and PD-L2 expression to foster an immunosuppressive tumor microenvironment, which mediates tumor immune evasion and drug resistance. Interestingly, TFEB also regulated HLA-A expression, which increases the tumor immunogenicity of OC. Finally, in a syngenic murine model of OC, we observed the therapeutic benefit of CDDP plus programmed cell death-1 (PD-1) inhibitor, which enhanced the cytolytic activity of CD8+ T cells and inhibited tumor growth. Our study illustrates the important role of TFEB in regulating the tumor immune microenvironment in OC.

Abstract Background Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni. Results We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was “Ribosome” in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells. Conclusions Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.

Abstract Objective To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

This experiment simulated the hypoxic environment caused by actual production operations in fish farming (i.e., catching, gathering, transferring, and weighting) to study the effects of acute hypoxic conditions on the physiological and metabolic responses of triploid rainbow trout (O. mykiss). Two groups of fish weighting 590 g were sampled in the normoxia group (dissolved oxygen above 7 mg/L) and hypoxia group (dissolved oxygen ranged from 2 to 5 mg/L for 10 min). The results showed that 1) regarding stress response, hypoxia increased plasma levels of cortisol, heat shock protein 70 (HSP-70), lysozyme, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine phosphokinase (CPK); induced the expression of hepatic genes encoding nuclear factor erythroid 2 related factor 2 (Nrf2), interferon γ (IFN-γ) and interleukin-1β (IL-1β). 2) Regarding metabolism response, hypoxia increased plasma levels of globulin (GLOB), glucose (GLU), triglyceride (TG) and lactate dehydrogenase (LDH); upregulated the hepatic gene expression of phosphoenolpyruvate carboxykinase, (PEPCK), pyruvate dehydrogenase kinase (PDK1), acetyl-CoA carboxylase (ACC) and acetyl-CoA oxidase (ACO); downregulated the hepatic gene expression of carnitine palmitoyl transferase 1 (CPT1); and unchanged the expression of hepatic genes in glycolysis and autophagy. 3) In response to hypoxia-inducible factors (HIFs), the hepatic HIF-2α gene was activated in the hypoxia group, but HIF-1α gene expression remained unchanged. Thus, during acute hypoxic stress, triploid rainbow trout were in a defensive state, with an enhanced immune response and altered antioxidant status. Additionally, the hepatic mitochondrial oxidation of glucose- and lipid-derived carbon in trout was suppressed, and hepatic gluconeogenesis and lipid synthesis were activated, which might be regulated by the HIF-2α pathway.

Abstract Background Uterine angioleiomyoma is a rare variant of leiomyoma, and the main therapy is complete surgery. This study introduces the benefit of three-dimensional computed tomography reconstruction for preoperative preparation. Case presentation A 50-year-old woman presented because of chest distress after activity, with worsening symptoms. After examination, the final diagnosis was uterine angioleiomyoma. The tumour originated in the uterus; grew into the right iliac vein; coursed along the iliac vein, inferior vena cava, and right atrium; and finally invaded the right ventricle. To best complete the surgery, a multidisciplinary surgery was selected. Before the surgery, a three-dimensional computed tomography reconstruction model was created to assess the tumour status, and this model enabled the surgery to be completed successfully. Conclusion Three-dimensional computed tomography reconstruction is of great significance for the preoperative diagnosis of uterine angioleiomyoma and the formulation of surgical treatment plans. Based on its vivid images, surgeons can perform operations more effectively and safely.

Previous studies report significant changes on biotic communities caused by cascade reservoir construction. However, factors regulating the spatial–temporal plankton patterns in alpine cascade reservoir systems have not been fully explored. The current study explored effects of environmental factors on the longitudinal plankton patterns, through a 5-year-long study on the environmental factors and communities of phytoplankton and zooplankton in an alpine cascade reservoir system located upstream of Yellow River region. The findings showed that phytoplankton and zooplankton species numbers in the studied cascade reservoir system were mainly regulated by the hydrological regime, whereas nutrient conditions did not significantly affect the number of species. Abundance and biovolume of phytoplankton in cascade reservoirs were modulated by the hydrological regime and nutrient conditions. The drainage rate, N:P ratio, and sediment content in cascade reservoirs were negatively correlated with abundance and biovolume of phytoplankton. Abundance and biovolume of zooplankton were not significantly correlated with the hydrological regime but showed a strong positive correlation with nutrient conditions in cascade reservoirs. Shannon–Wiener index (H’) and the Pielou index (J) of phytoplankton were mainly regulated by the hydrological regime factors, such as drainage rate and sediment content in cascade reservoirs. However, temperature and nutrient conditions were the main factors that regulated the Shannon–Wiener index (H’) and the Pielou index (J) of zooplankton. Species number, abundance, and biovolume of phytoplankton showed a significant positive correlation with those of zooplankton. Hydrodynamics and nutrient conditions contributed differently in regulating community structure of phytoplankton or zooplankton. These findings provide an understanding of factors that modulate longitudinal plankton community patterns in cascade reservoir systems.

Organoleptic properties and nutritional value are the most important characteristics of fish fillet quality, which can be determined by a series of quality evaluation indexes and closely related to fish nutrition. Systematic organoleptic and nutritional quality evaluation indexes consisting of 139 indexes for physical properties and chemical compositions of triploid rainbow trout were established. Besides, effects of dietary lipid levels (6.6%, 14.8%, 22.8% and 29.4%) on the quality of triploid rainbow trout were analyzed in the study. The main results showed that, for fillet appearance quality, fish fed diets with lipid levels above 22.8% had higher fillet thickness and redness but lower gutted yield and fillet yield (p < 0.05). For fillet texture, fish fed the diet with a 6.6% lipid level had the highest fillet hardness (5.59 N) and lowest adhesiveness (1.98 mJ) (p < 0.05), which could be related to lipid, glycogen, water soluble protein and collagen contents of the fish fillet. For fillet odor, the odor intensity of “green, fatty and fishy” significantly increased with the increase of the dietary lipid level (from 1400 to 2773 ng/g muscle; p < 0.05), which was related to the degradation of n-6 and n-9 fatty acids. For fillet taste, a high lipid diet (≥22.8%) could increase the umami taste compounds contents (from 114 to 261 mg/100 g muscle) but decrease the bitterness and sourness taste compounds contents (from 127 to 106 mg/100 g muscle and from 1468 to 1075 mg/100 g muscle, respectively) (p < 0.05). For nutritional value, a high lipid diet could increase the lipid nutrition level (such as the content of long chain polyunsaturated fatty acids increased from 3.47 to 4.41 g/kg muscle) but decease tryptophan and selenium content (from 2.48 to 1.60 g/kg muscle and from 0.17 to 0.11 g/kg muscle, respectively). In total, a high lipid diet could improve the quality of triploid rainbow trout. The minimum dietary lipid level for triploid rainbow trout should be 22.8% to keep the better organoleptic and nutritional quality.

Photothermal therapy (PTT), as a noninvasive and local treatment, has emerged as a promising anti-tumor strategy with minimal damage to normal tissue under spatiotemporally controllable irradiation. However, the necrosis of cancer cells during PTT will induce an inflammatory reaction, which may motivate tumor regeneration and resistance to therapy. In this study, polyoxometalates and a chloroquine diphosphate (CQ) co-loaded metal–organic framework nanoplatform with hyaluronic acid coating was constructed for efficient ovarian cancer therapy and anti-inflammation. Our results demonstrated that this nanoplatform not only displayed considerable photothermal therapeutic capacity under 808 nm near-infrared laser, but also had an impressive anti-inflammatory capacity by scavenging reactive oxygen species in the tumor microenvironment. CQ with pH dependence was used for the deacidification of lysosomes and the inhibition of autophagy, cutting off a self-protection pathway induced by cell necrosis–autophagy, and achieving the synergistic treatment of tumors. Therefore, we combined the excellent properties of these materials to synthesize a nanoplatform and explored its therapeutic effects in various aspects. This work provides a promising novel prospect for PTT/anti-inflammation/anti-autophagy combinations for efficient ovarian cancer treatment through the fine tuning of material design.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dualmodality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules. [ABSTRACT FROM AUTHOR]

The velvet antler is a unique model for cancer and regeneration research due to its periodic regeneration and rapid growth. Antler growth is mainly triggered by the growth center located in its tip, which consists of velvet skin, mesenchyme and cartilage. Among them, cartilage accounts for most of the growth center. We performed an integrative analysis of the antler cartilage transcriptome and proteome at different antler growth stages. RNA-seq results revealed 24,778 unigenes, 19,243 known protein-coding genes, and 5535 new predicted genes. Of these, 2722 were detected with differential expression patterns among 30 d, 60 d, and 90 d libraries, and 488 differentially expressed genes (DEGs) were screened at 30 d vs. 60 d and 60 d vs. 90 d but not at 30 d vs. 90 d. Proteomic data identified 1361 known proteins and 179 predicted novel proteins. Comparative analyses showed 382 differentially expressed proteins (DEPs), of which 16 had differential expression levels at 30 d vs. 60 d and 60 d vs. 90 d but not at 30 d vs. 90 d. An integrated analysis conducted for DEGs and DEPs showed that gene13546 and its coding protein protein13546 annotated in the Wnt signaling pathway may possess important bio-logical functions in rapid antler growth. This study provides in-depth characterization of candidate genes and proteins, providing further insights into the molecular mechanisms controlling antler development.

The present study identified the volatile compounds profile in raw muscle of triploid rainbow trout with different marketable sizes (eviscerated weight: 2 kg, 3 kg and 4 kg, respectively). Six fish per each size treatment were sampled in a local commercial trout farm, then raw muscles of sampled fish were filleted to detect the volatile compounds by using the gas chromatography-mass spectrometry (GCMS) analysis coupled with automated solid-phase microextraction (SPME) system. Results showed that a total of 58 volatile compounds were identified in raw muscle of triploid rainbow trout, including aldehydes (20 species), ketones (6 species), alcohols (9 species), hydrocarbons (11 species), aromatics (6 species) and miscellaneous compounds groups (6 species). The subtotal estimated concentration of aldehydes group was significantly higher than those of the other volatile groups (P 0.05). Based on the principle component analysis and cluster analysis using the odor activity values of 21 odor-active compounds, the overall odors of raw muscle might be similar in triploid rainbow trout with different marketable sizes.

Two experiments were conducted to study the digestive enzyme activities in scaleless carp (Gymnocypris przewalskii) on the Qinghai-Tibetan Plateau. In experiment 1, the distribution of digestive enzymes in various digestive organs of G. przewalskii (body weight: 118.24 ± 9.48 g) was studied. Results showed that digestive enzyme specific activities in intestine were significantly higher than those in hepatopancreas (P