A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice.

Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a tripeptide, Ser-Arg-Pro (SRP), from Sipunculus nudus L. was employed, and its potential efficacy in AKI was assessed. Oral administration of SRP significantly alleviated Cd-induced kidney damage, leading to improved renal function and the attenuation of structural abnormalities. A network pharmacology analysis revealed the potential of SRP in renal protection by targeting various pathways, including mitogen-activated protein kinase (MAPK) signaling, inflammatory response, and apoptosis pathways. Mechanistic studies indicated that SRP achieves renal protection by inhibiting the activation of MAPK pathways (phosphorylation of p38, p56, ERK, and JNK) in the oxidative stress cascade, suppressing inflammatory responses (iNOS, Arg1, Cox2, TNF-α, IL-1ß, and IL-6), and restoring altered apoptosis factors (caspase-9, caspase-3, Bax, and Bcl-2). Hence, SRP has the potential to be used as a therapeutic agent for the treatment of Cd-induced nephrotoxicity.

The Effects of Shaking Duration on the Abundance and the Community of Aerobic Denitrifying Bacteria in Shrimp Pond Water and Sediment Samples.

With the rapid development of intensive aquaculture, the considerable release of nitrogenous organic compounds has become a serious threat to aquatic organisms. Currently, isolating autochthonous aerobic denitrifying bacteria (ADB) from aquaculture environments is essential for the biological elimination of nitrogenous pollutants. In this study, the enrichment of ADB from shrimp pond water and sediment samples was conducted under different shaking durations. The absolute abundance of total bacteria, nosZ-type, and the napA-type ADB was measured using qPCR. High-throughput sequencing of 16S rRNA, nosZ, and napA genes was performed to reveal the community structure of bacteria and ADB, respectively. Our data revealed that absolute abundance and the community structure of the total bacteria, nosZ-type and napA-type ADB, were significantly altered under different shaking durations. Specifically, the order Pseudomonadales, possessing both nosZ and napA genes, was significantly enriched in water and sediment samples under both 12/12 and 24/0 shaking/static cycles. However, in water samples, compared to the 24/0 shaking/static cycles, the 12/12 shaking/static cycles could lead to a higher enrichment rate of aerobic denitrification bacteria indicated by the higher absolute abundance of bacteria and the higher accounting percentage of orders Oceanospirillales and Vibrionales. Moreover, although the order Pseudomonadales notably increased under the 12/12 of shake/static cycle compared to the 24/0 shaking/static cycle, considering the relative higher abundance of ADB in 24/0 shaking/static cycle, the enrichment of ADB in sediment may be efficient with the 24/0 shaking/static cycle.

Genomic Insights into the Origin and Evolution of Molluscan Red-Bloodedness in the Blood Clam Tegillarca granosa.

Blood clams differ from their molluscan kins by exhibiting a unique red-blood (RB) phenotype; however, the genetic basis and biochemical machinery subserving this evolutionary innovation remain unclear. As a fundamental step toward resolving this mystery, we presented the first chromosome-level genome and comprehensive transcriptomes of the blood clam Tegillarca granosa for an integrated genomic, evolutionary, and functional analyses of clam RB phenotype. We identified blood clam-specific and expanded gene families, as well as gene pathways that are of RB relevant. Clam-specific RB-related hemoglobins (Hbs) showed close phylogenetic relationships with myoglobins (Mbs) of blood clam and other molluscs without the RB phenotype, indicating that clam-specific Hbs were likely evolutionarily derived from the Mb lineage. Strikingly, similar to vertebrate Hbs, blood clam Hbs were present in a form of gene cluster. Despite the convergent evolution of Hb clusters in blood clam and vertebrates, their Hb clusters may have originated from a single ancestral Mb-like gene as evidenced by gene phylogeny and synteny analysis. A full suite of enzyme-encoding genes for heme synthesis was identified in blood clam, with prominent expression in hemolymph and resembling those in vertebrates, suggesting a convergence of both RB-related Hb and heme functions in vertebrates and blood clam. RNA interference experiments confirmed the functional roles of Hbs and key enzyme of heme synthesis in the maintenance of clam RB phenotype. The high-quality genome assembly and comprehensive transcriptomes presented herein serve new genomic resources for the super-diverse phylum Mollusca, and provide deep insights into the origin and evolution of invertebrate RB.

Novel Antioxidant Peptides from Crassostrea Hongkongensis Improve Photo-Oxidation in UV-Induced HaCaT Cells.

Enzymatic hydrolysates from Oysters (OAH) display multiple biological activities. Previously, a 3~5 KDa oyster ultrafiltration component (OUP) showed a high property of preventing skin oxidation. Subsequently, we identified specific peptides with such activity. OUP was fractionated stepwise by Sephadex-G25 and RP-HPLC, and active fractions were screened using UV-irradiated HaCaT cells. The most active fractions (OP5-3) were analyzed by LC-MS/MS and a total of 17 peptides were identified. Results from mass spectrometry showed that OP5-3 consisted of peptides with a molecular weight range of 841.51-1786.92 Da. Six of these peptides were synthesized for validating the activity of resisting skin oxidation in the same cell model. All six peptides showed varying degrees of antioxidant activity, while pretreatment of HaCaT cells with AIVAEVNEAAK alleviated UV cytotoxicity, inhibited metalloproteinase 1 (MMP-1) expression, and showed the highest activity to resist UV-induced skin photo-oxidation among these peptides. In addition, results from molecular docking analysis of MMP-1 with AIVAEVNEAAK showed that AIVAEVNEAAK suppresses its enzymatic activity by directly interacting with MMP-1 and thus exhibit anti-photoaging activity.

Purification and Identification of Peptides from Oyster (Crassostrea hongkongensis) Protein Enzymatic Hydrolysates and Their Anti-Skin Photoaging Effects on UVB-Irradiated HaCaT Cells.

This study aimed to purify and identify antiphotoaging peptides from oyster (Crassostrea hongkongensis) protein enzymatic hydrolysates (OPEH) and to investigate the possible mechanism underlying its antiphotoaging effect. Multiple methods (Ultrafiltration, G25 Chromatography, RP-HPLC, and LC/MS/MS) had been used for this purpose, and eventually, two peptides, including WNLNP and RKNEVLGK, were identified. Particularly, WNLNP exerted remarkable antiphotoaging effect on the UVB-irradiated HaCaT photoaged cell model in a dose-dependent manner. WNLNP exerted its protective effect mainly through inhibiting ROS production, decreasing MMP-1 expression, but increasing extracellular pro-collagen I content. Furthermore, WNLNP downregulated p38, JNK, ERK, and p65 phosphorylation in the MAPK/NF-κB signaling pathway and attenuated bax over-expressions but reversed bcl-2 reduction in UVB- irradiated HaCaT cells. The molecular docking analysis showed that WNLNP forms five and seven hydrogen bonds with NF-κB (p65) and MMP-1, respectively. This study suggested that a pentapeptide WNLNP isolated from OPEH had great potential to prevent and regulate skin photoaging.

The Potential Protective Effect and Possible Mechanism of Peptides from Oyster (Crassostrea hongkongensis) Hydrolysate on Triptolide-Induced Testis Injury in Male Mice.

Peptides from oyster hydrolysate (OPs) have a variety of biological activities. However, its protective effect and exact mechanism on testicular injury remain poorly understood. This study aimed to evaluate the protective effect of OPs on triptolide (TP)-induced testis damage and spermatogenesis dysfunction and investigate its underlying mechanism. In this work, the TP-induced testis injury model was created while OPs were gavaged in mice for 4 weeks. The results showed that OPs significantly improved the sperm count and motility of mice, and alleviated the seminiferous tubule injury. Further study showed that OPs decreased malonaldehyde (MDA) level and increased antioxidant enzyme (SOD and GPH-Px) activities, attenuating oxidative stress and thereby reducing the number of apoptotic cells in the testis. In addition, OPs improved the activities of enzymes (LDH, ALP and ACP) related to energy metabolism in the testis and restored the serum hormone level of mice to normal. Furthermore, OPs promoted the expression of Nrf2 protein, and then increased the expression of antioxidant enzyme regulatory protein (HO-1 and NQO1) in the testis. OPs inhibited JNK phosphorylation and Bcl-2/Bax-mediated apoptosis. In conclusion, OPs have a protective effect on testicular injury and spermatogenesis disorders caused by TP, suggesting the potential protection of OPs on male reproduction.

Ameliorative Effects of Peptides from the Oyster (Crassostrea hongkongensis) Protein Hydrolysates against UVB-Induced Skin Photodamage in Mice.

Chronic exposure to ultraviolet B (UVB) irradiation is a major cause for skin photoaging. UVB induces damage to skin mainly by oxidative stress, inflammation, and collagen degradation. This paper investigated the photo-protective effects of peptides from oyster (Crassostrea hongkongensis) protein hydrolysates (OPs) by topical application on the skin of UVB-irradiated mice. Results from mass spectrometry showed that OPs consisted of peptides with a molecular weight range of 302.17-2936.43 Da. In vivo study demonstrated that topical application of OPs on the skin significantly alleviated moisture loss, epidermal hyperplasia, as well as degradation of collagen and elastin fibers caused by chronic UVB irradiation. In this study, OPs treatment promoted antioxidant enzymes (SOD and GPH-Px) activities, while decreased malondialdehyde (MDA) level in the skin. In addition, OPs treatment significantly decreased inflammatory cytokines (IL-1ß, IL-6, TNF-α) content, and inhibited inflammation related (iNOS, COX-2) protein expression in the skin. Via inhibiting metalloproteinase 1(MMP1) expression, OPs treatment markedly decreased the degradation of collagen and elastin fibers as well as recovered the altered arrangement of extracellular matrix network in the dermis of skin. Our study demonstrated for the first time that OPs protected against UVB induced skin photodamage by virtue of its antioxidative and anti-inflammatory properties, as well as regulating the abnormal expression of MMP-1. The possible molecular mechanism underlying OPs anti-photoaging is possibly related to downregulating of the MAPK/NF-κB signaling pathway, while promoting TGF-ß production in the skin.

EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression.

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1ß were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

Forkhead box C1 boosts triple-negative breast cancer metastasis through activating the transcription of chemokine receptor-4.

The transcription factor forkhead box C1 (FOXC1) has recently been proposed as a crucial regulator of triple-negative breast cancer (TNBC) and associated with TNBC metastasis. However, the mechanism of FOXC1 in TNBC development and metastasis is elusive. In this study, overexpression of FOXC1 in MDA-MB-231 cells significantly enhanced, whereas knockdown of FOXC1 in BT549 cells significantly reduced, the capabilities of TNBC cell invasion and motility in vitro and metastasis to the lung in vivo, when compared to their respective control cells. Mechanistic studies revealed that FOXC1 increased the expression of CXC chemokine receptor-4 (CXCR4), probably through transcriptional activation. AMD3100, an inhibitor of CXCR4, could block cell migration. In a zebrafish tumor model, AMD3100 could suppress cell invasion and metastasis. In addition, overexpressing CXCR4 in FOXC1-knockdown BT549 cells increased the capabilities of TNBC cell invasion and motility. In contrast, inhibition of CXCR4 with either AMD3100 or siRNA in MDA-MB-231 cells overexpressing FOXC1 reduced the capabilities of invasion and motility. Taken together, our results reveal a potential mechanism for FOXC1-induced TNBC metastasis.

Proteasome Inhibitor MG132 Enhances Sensitivity to Cisplatin on Ovarian Carcinoma Cells In Vitro and In Vivo.

BACKGROUND: Platinum-based combination chemotherapy after surgery is considered a standard treatment; therefore, any recent drug development should be new, effective, and low toxic, and should have a synergistic effect with platinum. This study aimed to observe the growth of SKOV3 cells after treatment with cisplatin by combining with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and to investigate the effect of the relationship between MG132 and cisplatin combination. MATERIALS AND METHODS: Cell growth was detected by methyl thiazolyl tetrazolium assay after treatment with MG132 at 0.5, 1.5, 2.5, 3.5, and 5.0 µg/mL concentrations for 24, 48, and 72 hours; with cisplatin at 1.0, 2.0, 3.0, 4.0, and 5.0 µg/mL concentrations; and with combination with MG132 at 1.5 µg/mL for 24 hours. The apoptotic rates of cells were detected by a flow cytometer after cisplatin treatment at 1.0, 2.0, 3.0, and 4.0 µg/mL concentrations and that combined with MG132 at 1.5 µg/mL concentration for 12, 24, and 36 hours. A total of 20 BALB/c (nu/nu) female nude mice (age, 4-6 weeks; body weight, 17-19 g) were divided into 4 groups: control, MG132, cisplatin, and combination groups. The expression of Caspase3 and Beclin1 was detected by Western blot analysis and reverse transcription-polymerase chain reaction after treatment with 3.0 µg/mL of the cisplatin group and combined treatment with 1.5 µg/mL of MG132 group for 24 hours, respectively. RESULTS: Methyl thiazolyl tetrazolium assay demonstrated the inhibitory rates, and the flow cytometery showed that the apoptotic rates in the combination group were higher than those in the cisplatin group (P < 0.01). Western blot analysis and reverse transcription-polymerase chain reaction detected that Caspase3 and Beclin1 at a relative quantity in the combination group were higher than those in the cisplatin group (P < 0.05). CONCLUSIONS: MG132 has a synergistic antitumor effect by combining with cisplatin, and it is expected to be an effective antitumor drug for platinum-resistant refractory ovarian cancer.

Safety and Efficacy of Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Radical Surgery Alone in Locally Advanced Cervical Cancer Patients.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with locally advanced cervical cancer (LACC). METHODS: Eight hundred patients with LACC received either NACT followed by RS (NACT-RS) or RS alone. The primary outcome measures assessed the efficacy and adverse effects of NACT. Secondary outcome measures compared the preoperative clinical stage to the postoperative pathologic stage in NACT-RS and RS patients, assessed intraoperative and postoperative complications, including the adverse effects of postoperative radiotherapy and radiochemotherapy, and estimated the 5-year progression-free survival and 5-year overall survival. RESULTS: The clinical response to NACT was 89.54%. Patients in the NACT-RS group had lower preoperative hemoglobin levels (115.20 vs 122.04 g/L, P < 0.001), a longer operative time (mean, 233.66 vs 224.37 minutes, P = 0.008), more intraoperative bleeding (750.34 vs 684.41 mL, P = 0.011), a shorter duration of catheter use (mean, 29.84 vs 32.14 days, P = 0.036), and a lower incidence of postoperative complications (7.30% vs 13.62%, P = 0.002) and postoperative radiotherapeutic and radiochemotherapeutic adverse effects (3.16% vs 4.63%, P < 0.001) compared to patients in the RS group. The 5-year progression-free survival and 5-year overall survival were 80.30% and 81.10% in the NACT-RS group and 81.00% and 78.50% in the RS group (P > 0.05). Pathological poor differentiation, nonsquamous cell carcinoma, parametrial invasion, positive pelvic lymph node, and lymphovascular invasion (P < 0.05) were independent risk factors for recurrence. CONCLUSIONS: Neoadjuvant chemotherapy may reduce RS-associated complications and postoperative radiotherapeutic and radiochemotherapeutic adverse effects in Chinese patients with LACC.

Expression and localization of maspin in cervical cancer and its role in tumor progression and lymphangiogenesis.

OBJECTIVES: Cervical cancer is the most common malignant tumor in female reproductive tract and primarily metastasizes through the lymphatic system that will affect prognosis of patients. Maspin, a member of the serine protease inhibitors (serpins) super family, has recently been indicated as a tumor suppressor in many cancers. In this study, we investigated the clinical significance of maspin expression, especially the subcellular location of maspin and its functional role in progression and lymphangiogenesis, in cervical squamous cell carcinoma. METHODS: Labelled streptavidin biotin method (LSAB) was used to determine cytoplasmic and nuclear maspin expressions, respectively, in 13 cases of normal cervix, 15 cases of cervical intraepithelial neoplasia grade 3 (CIN3), 62 cases of squamous cell carcinoma (SCC) of the uterine cervix, and 13 cases of pelvic lymphatic nodes which were all positive lymphatic nodes in our selected cancer cases. LSAB is also used to detect podoplanin which is used for counting density of lymphatic microvessels (LMVD). The clinical significance of subcellular maspin expression and the relationship between maspin expression and LMVD in cervical cancer are analyzed. RESULTS: Both cytoplasmic and nuclear maspin expressions in SCC were significantly weaker than those of normal cervix and CIN3. Nuclear maspin expression showed a peak in CIN3 and then dropped in SCC. Declined maspin expression was correlated with later clinical stage, increased LMVD, and lymphatic metastasis. CONCLUSIONS: Our results suggest that subcellular location of maspin expression is a potential predictive factor in tumor progression and in patients' prognosis of cervical cancer, and maspin plays a suppression role in lymphangiogenesis and metastasis.

The transcriptomic and biochemical responses of blood clams (Tegillarca granosa) to prolonged intermittent hypoxia.

The blood clam (Tegillarca granosa), a marine bivalve of ecological and economic significance, often encounters intermittent hypoxia in mudflats and aquatic environments. To study the response of blood clam foot to prolonged intermittent hypoxia, the clams were exposed to intermittent hypoxia conditions (0.5 mg/L dissolved oxygen, with a 12-h interval) for 31 days. Initially, transcriptomic analysis was performed, uncovering a total of 698 differentially expressed genes (DEGs), with 236 upregulated and 462 downregulated. These genes show enrichments in signaling pathways related to glucose metabolism, sugar synthesis and responses to oxidative stress. Furthermore, the activity of the enzyme glutathione peroxidase (GPx) and the levels of gpx1 mRNA showed gradual increases, reaching their peak on the 13th day of intermittent hypoxia exposure. This observation suggests an indirect protective role of GPx against oxidative stress. The results of this study make a significantly contribute to our broader comprehensive of the physiological, biochemical responses, and molecular reactions governing the organization of foot muscle tissue in marine bivalves exposed to prolonged intermittent hypoxic conditions.

Observation of Agonistic Behavior in Pacific White Shrimp (Litopenaeus vannamei) and Transcriptome Analysis.

Agonistic behavior has been identified as a limiting factor in the development of intensive L. vannamei aquaculture. However, the characteristics and molecular mechanisms underlying agonistic behavior in L. vannamei remain unclear. In this study, we quantified agonistic behavior through a behavioral observation system and generated a comprehensive database of eyestalk and brain ganglion tissues obtained from both aggressive and nonaggressive L. vannamei employing transcriptome analysis. The results showed that there were nine behavior patterns in L. vannamei which were correlated, and the fighting followed a specific process. Transcriptome analysis revealed 5083 differentially expressed genes (DEGs) in eyestalk and 1239 DEGs in brain ganglion between aggressive and nonaggressive L. vannamei. Moreover, these DEGs were primarily enriched in the pathways related to the energy metabolism process and signal transduction. Specifically, the phototransduction (dme04745) signaling pathway emerges as a potential key pathway for the adjustment of the L. vannamei agonistic behavior. The G protein-coupled receptor kinase 1-like (LOC113809193) was screened out as a significant candidate gene within the phototransduction pathway. Therefore, these findings contribute to an enhanced comprehension of crustacean agonistic behavior and provide a theoretical basis for the selection and breeding of L. vannamei varieties suitable for high-density aquaculture environments.

[The regulation mechanism of MASPIN expression in ovarian carcinoma].

OBJECTIVE: To study the regulation of P63 on expression of MASPIN in ovarian cancer by observe MASPIN promoter activity changes before and after transient transfection of constructed P63 and MASPIN reporter gene plasmids. METHODS: The MASPIN reporter plasmid, fused with luciferase reporter gene, was constructed and transfected into SKOV3 cells together with P63 (TAP63, ANP63) express plasmid transiently. The MASPIN promoter activity was determined in both the transfected cells and controlled ones by Luciferase Assays and the transcription of MASPIN mRNA of them was evaluated with semi quantitative RT-PCR. RESULTS: The MASPIN reporter plasmid was successfully constructed and transiently transfected into SKOV3 cells together with P63 (TAP63, ANP63) expression plasmid. The data showed among the tested P63 splice variants, TAP63 remarkably activated MASPIN promoter transactivation (P < 0.05). No significant difference in the activity level of MASPIN promoter was detected in the SKOV3-vector and SKOV3-ANP63 cells (P > 0.05). The level of MASPIN mRNA expression was notably enhanced in SKOV3-TAP63 cell after transient transfected with TAP63 express plasmid (P < 0.05), but no significant difference among the SKOV3, SKOV3-vector and SKOV3-ANP63 cell (P > 0.05) was detected. CONCLUSION: TAP63 can activate the transcription activity of MASPIN promoter, as well as regulate the expression of MASPIN. Put all together, these results suggested that MASPIN is a new molecular target of P63.

Cadmium-chelating ability of the siderophore DHBS secreted by Leclercia adecarboxylata FCH-CR2 and its action mechanism.

As one of the most accumulative toxic heavy metals, cadmium (Cd) poses a major threat to human health. Bacterial siderophores, as small molecules with metal-absorbing ability, have great potential activity for Cd-reduction. In this study, the siderophore-producing bacterialstrain FCH-CR2 was isolated from a high-Cd contaminated soil using the CAS method. Leclercia adecarboxylata was identified through 16S rRNA sequence, homology analysis, colony morphology, physiological and biochemical tests. A siderophore, catechol type 2,3-dihydroxy-N-benzoyl-l-serine (DHBS) secreted by FCH-CR2, was purified using RP-HPLC and identified by LC-MS/MS. Intraperitoneal injection of DHBS significantly increased fecal Cd levels, and reduced Cd accumulation in organs. In density flooding theory (DFT) analysis, DHBS may bind to Cd via the hydroxyl site on the benzene ring. Besides, the isothermal titration calorimetry (ITC) assay revealed that the formation of Cd-DHBS is a spontaneous and endothermic reaction with ΔG = -21.4 kJ/mol and ΔH = 1.51 ± 0.142 kJ/mol.

Uterine cervical malignant granular cell tumor.

Malignant granular cell tumor is relatively uncommon, constituting only 1-2% of all granular cell tumors. It is a rare and unusual tumor, especially in non-typical sites, such as the uterine cervix, and grows more rapidly than benign granular cell tumor. It can be treated with surgical excision, but recurrence is possible and prognosis can be poor. A malignant granular cell tumor in the uterine cervix of a 37-year-old woman was incidentally diagnosed. The patient has a history of irregular vaginal bleeding. Uterine cervical biopsy under colposcope revealed a malignant granular cell tumor. After isophosphamide, etoposide, and cisplatin neoadjuvant chemotherapy, surgery was performed on the lesion, which approximately involved half the depth of cervical stroma. Computed tomography examination showed no local recurrence or distant metastasis during the 26-month follow-up period.

Hypoxia-mediated immunotoxicity in the blood clam Tegillarca granosa.

In marine ecosystems, dissolved oxygen (DO) is essential for maintaining intracellular energy balance during aerobic metabolism. Bivalve mollusks are frequently exposed to hypoxia environments due to tides, temperature changes, and anthropogenic activities. The blood clam, Tegillarca granosa, mainly inhabits intertidal mudflats and is more susceptible to low oxygen events. In this study, we investigated the effect of hypoxia on immune responses in clams, and showed that hypoxia exposure reduced total hemocyte counts (THC), hemoglobin concentrations, and intracellular reactive oxygen species (ROS) levels. Also, phagocytic and cell activities of hemocyte were significantly inhibited. Furthermore, immune-related gene expression was also down-regulated. In conclusion, hypoxia greatly affected immune functions in blood clams, and our research provided the foundation for further mechanistic studies on hypoxia tolerance in clams.

Case report: cotyledonoid dissecting leiomyoma in a 49-year-old woman.

Background: Cotyledonoid dissecting leiomyoma (CDL) is much less common than typical leiomyoma. Macroscopically, it displays multinodular, exophytic, placenta-like cystic masses and extends into the broad ligament, pelvic cavity, and retroperitoneal space. The seemingly malignant gross appearance of the tumor has perplexed gynecologists and pathologists; microscopically, it has no malignant characteristics, such as atypical cells, a high mitotic index, or tumor necrosis. To date, only a few cases of CDL have been reported. Here, we report a case of CDL, highlighting its gross and histological appearance, and present a review of the literature. Case Description: A 49-year-old woman presented with a history of progressive constipation of 6 months' duration and a palpable left lower abdominal mass of 1 month's duration. Transvaginal ultrasound revealed a bulky uterus containing 2 subserosal fibroids measuring 9.9 cm × 6.9 cm × 6.3 cm and 8.1 cm × 6.6 cm × 6.8 cm, respectively. An abdominal modified radical hysterectomy and bilateral salpingo-oophorectomy was performed. An intraoperative frozen section showed an angioleiomyoma with edema. However, the postoperative paraffin section confirmed a diagnosis of CDL. No abnormalities were observed at the 6-month follow-up visit. Conclusions: Despite its seemingly malignant gross appearance, CDL, based on its microscopic appearance, is a rare benign tumor and has a favorable prognosis.