Triplet pregnancy with hydatidiform mole: A report of two cases with literature review.

AIM: We present two cases of triplet pregnancy with complete hydatidiform mole (CHM) in contrasting outcomes and discuss the complications of mothers and outcomes of fetuses through a literature review, raising an important issue on the management of this special pregnancy. METHODS: We share our manage experience for two cases of triplet pregnancy with CHM and retrospectively analyze 18 similar pregnancies reported previously with different pregnancy outcomes. RESULTS: In our cases, one case receiving Clomiphene ovulation induction delivered two live fetuses by cesarean section at 30+ weeks without GTN (gestational trophoblastic neoplasia), unfortunately, the other case following ICSI-ET terminated the pregnancy in the setting of complications at 18+ weeks without GTN. No severe complications were detected during pregnancy and no pGTD was developed after delivery in neither of the pregnant. CONCLUSIONS: Co-existing complete hydatidiform mole in multiple pregnancies may become more common owing to the spreading use of ART. The decision for whether continue pregnancy depending on the personalized conditions including the complications of the pregnancy, the outcomes of the fetuses, the gestational age for delivery, and the potential progression of persistent gestational trophoblastic disease (pGTD). Furthermore, close monitor is necessary for the pregnant with triplet pregnancy with CHM who want to continue pregnancy.

Systematic retrospective analysis of 13 cases of uterine arteriovenous fistula: Pathogeny, diagnosis, treatment and follow-up.

AIM: To analyze the causes, clinical manifestations, diagnosis and treatment of uterine arteriovenous fistula (UAVF). METHODS: We retrospectively analyzed 13 patients with UAVF admitted to our hospital from October 2016 to April 2019. RESULTS: All patients had a history of intrauterine surgery (curettage for abortion, artificial removal of placenta, hysteroscopy, diagnostic curettage and intrauterine device removal). The main clinical manifestation of UAVF is paroxysmal massive vaginal bleeding; this involved a massive gush of vaginal blood that stopped suddenly. Sonographic images with typical features of UAVF were observed for 12 patients. Pelvic contrast-enhanced magnetic resonance imaging was performed as a noninvasive adjuvant examination method for diagnosis. Twelve patients underwent uterine arteriography and a diagnosis of UAVF was confirmed. Then, bilateral uterine artery embolization (UAE) was performed. One patient underwent laparoscopic hysterectomy directly instead of uterine arteriography because of unstable vital signs and one patient underwent laparoscopic hysterectomy 25 weeks after the second UAE. The median time until menstrual recovery was 33 days (range, 20-70 days) after UAE. The median time until normal ultrasound examination results was 10 weeks (range, 2-35 weeks). CONCLUSION: Acquired UAVF was associated with a history of previous intrauterine surgery. The ultrasound examination and pelvic contrast-enhanced MRI were noninvasive adjuvant examination method to effectively assist in diagnosis. Uterine arteriography is considered the gold standard for the diagnosis of UAVF, and UAE is considered an effective intervention for treating UAVF and maintaining reproductive function with less damage. Hysterectomy is an appropriate option when conservative measures have failed to prevent a life-threatening hemorrhage.

Serum markers in the differential diagnosis of Waldenstrom macroglobulinemia and other IgM monoclonal gammopathies.

BACKGROUND: IgM monoclonal gammopathy can be present in a broad spectrum of diseases. We evaluated the value of serum markers in the differential diagnosis of Waldenstrom macroglobulinemia (WM) and other types of IgM monoclonal gammopathies. METHODS: We included patients who were first admitted to hospital and identified as having IgM monoclonal gammopathy by serum immunofixation electrophoresis (sIFE). We evaluated basic clinical features, sIFE, diagnosis, and serum markers. Furthermore, we applied the receiver operating characteristic (ROC) curve to analyze the differential diagnosis value of serum markers for WM. Finally, we used logistic regression and ROC curve to analyze the differential diagnosis value of multimarker combinations to identify WM. RESULTS: IgM monoclonal gammopathy was most frequently found in patients with Waldenstrom macroglobulinemia, followed by monoclonal gammopathy of undetermined significance (MGUS), B-cell non-Hodgkin Lymphoma (B-NHL), and multiple myeloma (MM). Serum markers showed significant differences among the four diseases. The diagnostic markers LDH, IgM, IgG, IgA, and serum light chain К had higher diagnostic efficiency. Among these markers, serum IgM provided the highest diagnostic efficiency. Additionally, the combined use of all five serum markers provided the most effective diagnosis. CONCLUSIONS: The five serum markers, LDH, IgM, IgG, IgA, and К, each yielded a specific efficacy in differential diagnosis of WM. The single marker with the highest diagnostic efficiency was the serum IgM level. However, a combination of multiple serum markers was better than the use of a single marker in diagnosing WM. The combined use of all five serum markers provided the most effective diagnosis, with an AUC of .952 and sensitivity and specificity of 87.8% and 86.9%, respectively.

Fragile X-related protein 1 (FXR1) regulates cyclooxygenase-2 (COX-2) expression at the maternal-fetal interface.

Cyclooxygenase-2 (COX-2) is regulated post-transcriptionally by the AU-rich element (ARE) in the 3'-untranslated region (UTR) of its mRNA. However, the mechanism of COX-2 induction in infertility has not been thoroughly elucidated to date. The aim of this study was to examine the association between COX-2 and fragile X-related protein 1 (FXR1) in trophoblasts. Using quantitative reverse transcription polymerase chain reaction, our results showed that FXR1 mRNA expression levels were significantly decreased in trophoblasts from recurrent miscarriage patients compared with healthy controls; conversely, COX-2 mRNA expression levels were increased in patient samples. We also observed that FXR1 was highly expressed in human placental villi during early pregnancy. Furthermore, we used western blotting and immunofluorescence to analyse the expression levels of FXR1 and COX-2 in HTR-8 cells that were treated with tumour necrosis factor α; we observed that the expression of COX-2 was clearly increased in HTR-8 cells treated with FXR1 small interfering RNA, whereas the expression of COX-2 was effectively decreased in HTR-8 cells with FXR1 overexpressed via a plasmid. Importantly, bioinformatics analysis identified FXR1 binding sites in the 3'-UTR region of COX-2 and firefly luciferase reporter assay analysis verified that FXR1 binds directly to the 3'-UTR region of COX-2. ELISA assays showed that overexpression of FXR1 enhanced vascular endothelial growth factor-A and interleukin-8 expression in HTR-8 cells, whereas conversely, knockdown of FXR1 effectively repressed these effects. In conclusion, the results of this study indicate that FXR1 is a novel COX-2 regulatory factor.

Effects of sertraline on executive function and quality of life in patients with advanced cancer.

BACKGROUND: The aim of this study was to investigate effects of the antidepressant sertraline on executive function and quality of life in patients with advanced cancer. MATERIAL/METHODS: We assigned 122 patients with stage III or IV cancer to the depressed group (DG, n=86) or the non-depressed group (NG, n=36). All subjects were given supportive treatment and patients in the DG received additional antidepressant treatment. RESULTS: There were significant differences in total scores of the Hamilton anxiety scale (HAMA) and the Hamilton depression scale (HAMD), performance in the Wisconsin card sorting test, and SF-36 domains. After antidepressant treatment, the level of depression and anxiety decreased significantly in the DG, but was still significantly higher than in the NG. Low executive function was enhanced in the DG, but a worsening executive function was found in total errors in the NG (-2.3±3.8) (P<0.05). The dimensions of SF-36 in physical functioning (PF), role limitations-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role limitations-emotional (RE), and mental health (MH) were decreased significantly at baseline in the DG compared to the NG (P<0.01). After 12-week Sertraline treatment, improvement in the DG in factors VT, SF, RE, and MH were more powerful than in the NG (P<0.05). HAMA, HAMD, and VAS scores and tumor stage were significantly correlated to any one dimension of quality of life. CONCLUSIONS: Depression is an important cause of decreased quality of life and executive function in patients with advanced cancer. The antidepressant sertraline can improve the executive function and quality of life, which may be helpful in the clinical practice of cancer treatment.

Clinical efficacy and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in gastrectomy.

BACKGROUND: With the continuous progress of surgical technology and improvements in medical standards, the treatment of gastric cancer surgery is also evolving. Proximal gastrectomy is a common treatment, but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options. Each of these two surgical methods has advantages and disadvantages, so it is particularly important to compare and analyze their clinical efficacy and safety. AIM: To compare the surgical safety, clinical efficacy, and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy. METHODS: The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study. According to the different anastomosis methods used, the patients were divided into a double-channel anastomosis group (50 patients) and a tubular gastroesophageal anastomosis group (49 patients). In the double-channel anastomosis, Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection, and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux. In the tubular gastroesophageal anastomosis group, after the proximal end of the stomach was cut, tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube. The main outcome measure was quality of life 1 year after surgery in both groups, and the evaluation criteria were based on the postgastrectomy syndrome assessment scale. The greater the changes in body mass, food intake per meal, meal quality subscale score, and total measures of physical and mental health score, the better the condition; the greater the other indicators, the worse the condition. The secondary outcome measures were intraoperative and postoperative conditions, the incidence of postoperative long-term complications, and changes in nutritional status at 1, 3, 6, and 12 months after surgery. RESULTS: In the double-channel anastomosis cohort, there were 35 males (70%) and 15 females (30%), 33 (66.0%) were under 65 years of age, and 37 (74.0%) had a body mass index ranging from 18 to 25 kg/m2. In the group undergoing tubular gastroesophageal anastomosis, there were eight females (16.3%), 21 (42.9%) individuals were under the age of 65 years, and 34 (69.4%) had a body mass index ranging from 18 to 25 kg/m2. The baseline data did not significantly differ between the two groups (P > 0.05 for all), with the exception of age (P = 0.021). The duration of hospitalization, number of lymph nodes dissected, intraoperative blood loss, and perioperative complication rate did not differ significantly between the two groups (P > 0.05 for all). Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group. Specifically, they had lower scores for esophageal reflux [2.8 (2.3, 4.0) vs 4.8 (3.8, 5.0), Z = 3.489, P < 0.001], eating discomfort [2.7 (1.7, 3.0) vs 3.3 (2.7, 4.0), Z = 3.393, P = 0.001], total symptoms [2.3 (1.7, 2.7) vs 2.5 (2.2, 2.9), Z = 2.243, P = 0.025], and other aspects of quality of life. The postoperative symptoms [2.0 (1.0, 3.0) vs 2.0 (2.0, 3.0), Z = 2.127, P = 0.033], meals [2.0 (1.0, 2.0) vs 2.0 (2.0, 3.0), Z = 3.976, P < 0.001], work [1.0 (1.0, 2.0) vs 2.0 (1.0, 2.0), Z = 2.279, P = 0.023], and daily life [1.7 (1.3, 2.0) vs 2.0 (2.0, 2.3), Z = 3.950, P < 0.001] were all better than those of the tubular gastroesophageal anastomosis group. The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score [3.0 (2.0, 4.0) vs 3.5 (2.0, 5.0) (Z = 2.345, P = 0.019] compared to the dual-channel anastomosis group. Hemoglobin, serum albumin, total serum protein, and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups (P > 0.05 for all). CONCLUSION: The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery. Compared with tubular gastric surgery, double-channel anastomosis is a preferred surgical technique for proximal gastric cancer. It offers advantages such as less esophageal reflux and improved quality of life.

Advanced Multifunctional Hydrogels for Enhanced Wound Healing through Ultra-Fast Selenol-SNAr Chemistry.

Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on-demand degradable hydrogels with multilevel responsiveness. By employing selenol-dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds-diselenide, aryl selenide, and dearomatized selenide-in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self-healing and on-demand degradation properties. Furthermore, the resulting material demonstrated light-triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se-Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se-Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se-Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.

Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant.

BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.

Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice.

AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome.

Application of Cell Membrane-Coated Nanomaterials for Tumor Treatment.

Tumors are a major cause of human mortality worldwide, and the rapid development of nanomaterials (NMs) for tumor therapy and drug delivery has provided new treatment methods. However, NMs' high immunogenicity, short circulation time, and low specificity limit their application in tumor therapy. In recent years, bionanomaterials using cell membranes have emerged to overcome the shortcomings of monomeric NMs. Cell membrane-encapsulated NMs extracted from multiple cells not only retain the physicochemical properties of NMs but also inherit the biological functions of the source cells, aiding in drug delivery. The combination of the cell membrane and drug-loading NMs offers an efficient and targeted drug delivery system tailored to the tumor microenvironment. The research and application of this method have been widely carried out in the academic field of tumor diagnosis and treatment. This review presents the recent research progress of cell membrane-coated NMs as drug carriers in tumor therapy, including cell membrane extraction methods, encapsulation strategies, and the applications of cell membrane-encapsulated NMs in tumor therapy. We believe that biomimetic nanomaterials will be a promising and novel anticancer strategy in the future, and their wide application will certainly bring vitality to the field of tumor diagnosis and treatment. The combination of membrane and drug-loading nanomaterials embodies a highly efficient and target drug delivery system tailored to the tumor microenvironment, which broadens a new path of drug delivery for future cancer treatment. Meanwhile, it is also a perfect combination and application of biomedical nanomaterials, which is of great significance.

Selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release for diabetic wound healing.

BACKGROUND: Multifunctional hydrogels with controllable degradation and drug release have attracted extensive attention in diabetic wound healing. This study focused on the acceleration of diabetic wound healing with selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release. METHODS: Herein, selenium-containing hybrid hydrogels, defined as DSeP@PB, were fabricated via the reinforcement of selenol-end capping polyethylene glycol (PEG) hydrogels by polydopamine nanoparticles (PDANPs) and Prussian blue nanozymes in a one-pot approach in the absence of any other chemical additive or organic solvent based on diselenide and selenide bonding-guided crosslinking, making them accessible for large-scale mass production. RESULTS: Reinforcement by PDANPs greatly increases the mechanical properties of the hydrogels, realizing excellent injectability and flexible mechanical properties for DSeP@PB. Dynamic diselenide introduction endowed the hydrogels with on-demand degradation under reducing or oxidizing conditions and light-triggered nanozyme release. The bioactivity of Prussian blue nanozymes afforded the hydrogels with efficient antibacterial, ROS-scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further animal studies indicated that DSeP@PB under red light irradiation showed the most efficient wound healing activity by stimulating angiogenesis and collagen deposition and inhibiting inflammation. CONCLUSION: The combined merits of DSeP@PB (on-demand degradation, light-triggered release, flexible mechanical robustness, antibacterial, ROS-scavenging and immunomodulatory capacities) enable its high potential as a new hydrogel dressing that can be harnessed for safe and efficient therapeutics for diabetic wound healing.

Indicators and medical tests to identify lower limb swelling causes after total knee arthroplasty: a Delphi study with multidisciplinary experts.

BACKGROUND: Lower limb swelling after total knee arthroplasty (TKA) hinders surgical effectiveness. The poor results of studies on swelling interventions are due to the lack of a classification of swelling causes through appropriate medical tests. A gold standard is missing. This study aimed to clarify the causes of TKA postoperative swelling and how to identify them through indicators and medical tests by consulting a wide range of experts from multiple disciplines. METHOD: The Delphi method was used. A first draft of the index was prepared based on a systematic search of the literature. A total of 11 experts from several disciplines were invited to evaluate the rationality of the indicators and suggest modifications. After two rounds of consultation, the experts reached a consensus, and the consultation was stopped. RESULTS: The response rate of the 11 experts was 100%, and the authoritative Cr was 0.896. Kendall's W values for opinion coordination of the two rounds of consultation were 0.262 and 0.226, respectively (P < 0.001). Among the final indicators, there were 4 primary indicators for swelling cause classification (inflammatory response, poor venous return, joint hematoma, muscle damage, and healing), 19 secondary and 19 tertiary indicators. CONCLUSION: The indications obtained by systematic literature review and multidisciplinary expert consultation are reliable and scientific. Multiple causes of lower extremity swelling after TKA were identified. Blood test indicators can reflect an inflammatory response, suggest poor venous return, and reflect muscle damage and healing progress. Ultrasound scans are needed to identify underlying thrombotic or valvular problems, joint hematomas, and muscle damage. These tests help clinicians and researchers determine the cause of swelling after TKA and take appropriate management.

Cytotoxic amide alkaloids from Piper boehmeriaefolium.

Eight new amide alkaloids (1-8) and 19 known ones were isolated from the whole plant of Piper boehmeriaefolium. Their structures were determined through spectroscopic data analyses. Cytotoxic activity of these amides against human cervical carcinoma HeLa cells was evaluated, and 1-[(9E)-10-(3,4-methylenedioxyphenyl)-9-decenoyl]pyrrolidine (9) exhibited significant inhibitory activity with an IC(50) value of 2.7 µg/mL.

[Hematologic Phenotype and Genotype Analysis of Patients with Hemoglobin Variants].

OBJECTIVE: To study the hematologic and molecular features of 14 patients with hemoglobin (Hb) variants, so as to provide reference data for its laboratory screening. METHODS: A total of 1 029 samples were screened by high performance liquid chromatography (HPLC) on the Bio-Rad VariantⅡHPLC system. GAP-PCR and reverse dot blot (RDB) were used to detect common mutation of α and ß globin gene in Chinese. DNA sequencing for α and ß globin gene was simultaneously performed in samples with abnormal spectrum peak and negative thalassemia gene. RESULTS: In 1 029 samples, 10 types of structural Hb variants were detected in14 cases (1.36%), including 1 case of Hb E / ß- thalassemia, 1 case of Hb E /α- thalassemia (HbH disease), 2 cases of HbG-Taipei, 2 cases of Hb Q-Thailand, 2 cases of Hb Youngstown, 1 case of Hb Guangzhou-Hangzhou, 1 case of Hb M-Boston, 1 case of Hb G-Siriraj, 1 case of Hb J-Baltimore, 1 case of Hb J-Sicilia and 1 case of Hb Tamano. CONCLUSION: The occurrence of abnormal structural Hb variants with many genotypes in Shanghai is unique. Except for Hb E, Hb Youngstown, and Hb M-Boston, other types of heterozygous are normal in phenotypes, and symptoms such as hemolysis and anemia often occur when other diseases are combined.

Multidecadal records of microplastic accumulation in the coastal sediments of the East China Sea.

Microplastics are an emerging hazard in the marine environment, and considered to eventually sink into sediments. An investigation into the long-term variation of microplastic accumulation in sediment cores is essential for understanding the historical trend of this contamination and its response to human activities. In this study, the multidecadal changes of microplastic abundances in two sediment cores from the inner shelf of the East China Sea (ECS) were revealed by two methods, i.e., a visual enumeration method based on scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) and a quantitative method based on microplastic-derived carbon (MPC) abundances. The features of microplastics were determined via SEM-EDS and micro-Fourier transform infrared spectroscopy (µ-FTIR). The results reveal a multidecadal increasing trend of microplastic accumulation in the coastal sediments of the ECS since the 1960s, which may be jointly governed by the release of plastic wastes and oceanographic dynamics. Meanwhile, the breakpoint of the exponential growth of microplastics in the ECS occurs in 2000 AD, which well matches the rapid increasing of plastic production and consumption in China. Further, based on the MPC contents in sediments, the influence of microplastics on the quantitative evaluation of carbon storage in the ECS has been examined for the first time, revealing an insignificant (<2% before 2014 AD) but potentially-increasing (6.8% by 2025 AD) contribution of microplastics to carbon burial. Our results may provide the important data for evaluating and mitigating the impact of microplastics on the marine environment.

A novel thermoanalytical method for quantifying microplastics in marine sediments.

Microplastic pollution in marine environments is of particular concern on its risk to the ecosystem. To assess and manage microplastic contaminants, their quantitative detection in environmental samples is a high priority. However, uncertainties of current methods still exist when estimating their abundances, particularly with fine-grained (<1 mm) microplastics. This work reports a novel thermoanalytical method for quantifying microplastics by measuring the contents of microplastic-derived carbon (MPC) in samples under the premise of nearly eliminating the limit of their particle appearances. After validating the method via samples with the spiked microplastics, we have conducted a case study on sediment core H43 that spanned 1925-2009 CE from the Yellow Sea for further illustrating the high reliability and practicability of this method for quantifying microplastics in natural samples. Our results have demonstrated that the proposed method may be a promising technique to determine the mass-related concentrations of the total microplastics in marine sediments for evaluating their pollution status and quantitative contribution to marine carbon storage.

Characterization of Matrix Metalloprotease-9 Gene from Nile tilapia (Oreochromis niloticus) and Its High-Level Expression Induced by the Streptococcus agalactiae Challenge.

The bacterial diseases of tilapia caused by Streptococcus agalactiae have resulted in the high mortality and huge economic loss in the tilapia industry. Matrix metalloproteinase-9 (MMP-9) may play an important role in fighting infection. However, the role of MMP-9 in Nile tilapia against S. agalactiae is still unclear. In this work, MMP-9 cDNA of Nile tilapia (NtMMP-9) has been cloned and characterized. NtMMP-9 has 2043 bp and encodes a putative protein of 680 amino acids. NtMMP-9 contains the conserved domains interacting with decorin and inhibitors via binding forces compared to those in other teleosts. Quantitative real-time-polymerase chain reaction (qPCR) analysis reveals that NtMMP-9 distinctly upregulated following S. agalactiae infection in a tissue- and time-dependent response pattern, and the tissues, including liver, spleen, and intestines, are the major organs against a S. agalactiae infection. Besides, the proteolytic activity of NtMMP-9 is also confirmed by heterologous expression and zymography, which proves the active function of NtMMP-9 interacting with other factors. The findings indicate that NtMMP-9 was involved in immune responses against the bacterial challenge at the transcriptional level. Further work will focus on the molecular mechanisms of NtMMP-9 to respond and modulate the signaling pathways in Nile tilapia against S. agalactiae invasion and the development of NtMMP-9-related predictive biomarkers or vaccines for preventing bacterial infection in the tilapia industry.

The m6A demethylase ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of CYR61 mRNA.

N6-Methyladenosine (m6A) is the most prevalent internal modification in mammalian mRNAs. Although m6A is important in many biological processes, its roles in the placenta are unclear. Methods: Levels of global mRNA m6A methylation and ALKBH5 expression in recurrent miscarriage (RM) patients were determined using quantitative reverse transcription-PCR (qRT-PCR), m6A RNA methylation quantification, and immunohistochemical methods. Using ALKBH5 overexpression and knockdown methods, we determined the role of ALKBH5 in trophoblast invasion at the maternal interface through trophoblasts and an extravillous explant culture experiments. Furthermore, the regulation of CYR61 by ALKBH5 was explored by RNA-sequencing coupled with methylated RNA immunoprecipitation. Results: We found that the level of global mRNA m6A methylation was significantly decreased in placental villous tissue from RM patients, while ALKBH5 expression was specifically unregulated. Furthermore, we demonstrated that ALKBH5 knockdown in human trophoblast promoted trophoblast invasion. Conversely, overexpression of ALKBH5 inhibited cell invasion. ALKBH5 knockdown promoted trophoblast invasion in villous explant culture experiments, while overexpression of ALKBH5 repressed these effects. Furthermore, we clarified that ALKBH5 inhibited trophoblast invasion by regulating CYR61 mRNA stability, and this RNA regulation is m6A dependent. Mechanistic analyses showed that decreased ALKBH5 in trophoblast increased the half-life of CYR61 mRNA and promoted steady-state CYR61 mRNA expression levels. Conclusions: We elucidated the functional roles of ALKBH5 and mRNA m6A methylation in trophoblast and identified a novel RNA regulatory mechanism, providing a basis for further exploration of broad RNA epigenetic regulatory patterns in RM diseases.

The orphan nuclear receptor NUR77 promotes trophoblast invasion at early pregnancy through paracrine placental growth factor.

NR4A1 (NUR77) is an orphan nuclear receptor that has been implicated in both cell survival and apoptosis. However, the role of NUR77 in trophoblast function during early placenta development has not been fully elucidated. In this study, we showed that NUR77 expression was significantly lower in the villi of the recurrent miscarriage (RM) group compared to that in the healthy controls (HCs) group. We used immunohistochemistry and found that NUR77 was highly expressed in human placental villi during early pregnancy, especially in syncytiotrophoblast (STB), and was expressed at a much lower level in STB from the RM group than in those from HC group. Western blotting data further confirmed that NUR77 was highly expressed in primary human term placental STB and the FSK-induced BeWo cell line. Moreover, antibody array screening and ELISA revealed that NUR77 promoted significant placental growth factor (PGF) expression during trophoblast fusion. Ectopic overexpression and knockdown experiments demonstrated that PGF was a novel downstream target of NUR77, and serum PGF expression correlated positively with trophoblast NUR77 mRNA levels in HCs and RM patients. Importantly, bioinformatics analysis identified two NUR77 binding sites in the PGF promoter region, and chromatin immunoprecipitation (ChIP) coupled with Western blotting analysis further verified that NUR77 bound directly to the PGF promoter region and promoted PGF expression. Furthermore, in a BeWo/HTR-8 co-culture system, FSK-induced BeWo-secreted PGF promoted HTR-8 cell migration and invasion, and an anti-PGF antibody reversed this effect. Collectively, these results indicated that NUR77 may play a key role in regulating trophoblast invasion at early pregnancy. KEY MESSAGES: NUR77 expression was significantly decreased in the syncytiotrophoblast of the recurrent miscarriage group compared to that in the healthy control group. NUR77 promoted PGF expression during trophoblast fusion. ChIP and western blotting experiments verified that NUR77 bound directly to the PGF promoter region and activated PGF expression in trophoblast. Trophoblast-derived PGF promoted HTR-8 cell migration and invasion in a cell co-culture system.

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology.

OBJECTIVE: The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. METHODS: Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro. A suspension of allogeneic UC-MSCs (1 × 106) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF-α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. RESULTS: Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF-α of the untreated control group were significantly higher than those of the treated group (P < 0.05) 7-14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference (P < 0.01). CONCLUSION: Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response.