Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion.

BACKGROUND: Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN. METHODS: IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1-2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers. RESULTS: The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker. CONCLUSIONS: Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.

Applications of Data Characteristic AI-Assisted Raman Spectroscopy in Pathological Classification.

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.

The use of intrauterine balloon therapy in reproductive medicine and surgery: a guidance for practice.

The use of balloon therapy in obstetric practice especially in postpartum haemorrhage (PPH) is well established and has recently been reviewed. However, little attention has been drawn regarding the use of intrauterine balloon (IUB) in gynaecological practice. This study focuses on the various usage of IUB in gynaecological practice. An electronic literature search through Medline, EMBASE and Clinicaltrial.gov from inception to August 2022 was conducted. The study focuses on the three following areas: (1) Indications: prevention and removal of intrauterine adhesions, management of ectopic pregnancy, facilitation of endoscopic surgery and other clinical usages; (2) Practical aspects of balloon therapy including ultrasound guidance, choice of balloon, inflation volume, duration of balloon therapy; and (3) Potential complications including pain, infection, uterine rupture and how they can be avoided. IUB therapy is a simple, inexpensive and effective method that can be applied in various gynaecological conditions ranging from IUA to intrauterine haemorrhage. Complications are rare, but in most cases can be avoided with correct use.

A new method for the treatment of myocardial ischemia-reperfusion injury based on γδT cell-mediated immune response.

Acute myocardial ischemia is a disease with high morbidity and mortality, and re-perfusion is currently the best intervention. However, re-perfusion may lead to further myocardial injury and increase the area of myocardial infarction. The mechanism of myocardial ischemia-re-perfusion injury is complex, but with more in-depth study, it has been proved that the immune system plays an important role in the process of MIRI. Among them, the γδT cell population has received increasing attention as the main early source of IL-17A in many immune response models. Because γδT cells have the characteristics of linking innate immunity and adaptive immunity,they can rapidly produce IL-17A and produce subsequent immune killing of cardiomyocytes. It can be seen that γδT cells play an important role in MIRI. Therefore, here we review the research progress of immune response in myocardial ischemia-re-perfusion injury, the key characteristics of γδT cells and the role of rapidly produced IL-17 in myocardial ischemia-re-perfusion injury, and propose relevant treatment strategies and prospects for myocardial repair, in order to provide new ideas and methods for clinical treatment of myocardial ischemia-re-perfusion injury.

A negative feedback loop between KLF9 and the EMT program dictates metastasis of hepatocellular carcinoma.

Metastasis is the primary cause of death of hepatocellular carcinoma (HCC), while the mechanism underlying this severe disease remains largely unclear. The Kruppel-like factor (KLF) family is one of the largest transcription factor families that control multiple physiologic and pathologic processes by governing the cellular transcriptome. To identify metastatic regulators of HCC, we conducted gene expression profiling on the MHCC97 cell series, a set of subclones of the original MHCC97 that was established by in vivo metastasis selection therefore harbouring differential metastatic capacities. We found that the expression of KLF9, a member of the KLF family, was dramatically repressed in the metastatic progeny clone of the MHCC97 cells. Functional studies revealed overexpression of KLF9 suppressed HCC migration in vitro and metastasis in vivo, while knockdown of KLF9 was sufficient to promote cell migration and metastasis accordingly. Mechanistically, we found the expression of KLF9 can reverse the pro-metastatic epithelial-mesenchymal transition (EMT) program via direct binding to the promoter regions of essential mesenchymal genes, thus repressing their expression. Interestingly, we further revealed that KLF9 was, in turn, directly suppressed by a mesenchymal transcription factor Slug, suggesting an intriguing negative feedback loop between KLF9 and the EMT program. Using clinical samples, we found that KLF9 was not only downregulated in HCC tissue compared to its normal counterparts but also further reduced in the HCC samples of whom had developed metastatic lesions. Together, we established a critical transcription factor that represses HCC metastasis, which is clinically and mechanically significant in HCC therapies.

Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor.

Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.

Case Report: From epilepsy and uterus didelphys to Turner syndrome-associated dysgerminoma.

Dysgerminoma is a rare occurrence in Turner syndrome patients without Y chromosome mosaicism or hormone therapy during puberty. We present a unique case of a 33-year-old nulliparous Chinese woman with intermittent epilepsy and Mullerian anomalies carrying a double uterus, cervix, and vagina. The patient is also characterized as having Turner syndrome accompanied by 46,X, del(Xp22.33-11.23) and del(2)(q11.1-11.2). MRI exhibited a 17.0 cm × 20.0 cm × 10.5 cm solid ovarian lesion. Radical surgery and pathology revealed dysgerminoma at stage IIIc with lymphatic metastases and a KIT gene mutation identified in exon 13. Furthermore, the tumor microenvironment (TME) displayed robust expression of CD4+ T lymphocytes and PD-1, whereas the distribution of CD8+ T lymphocytes and PDL-1 was sporadic. Despite the administration of enoxaparin to prevent thromboembolism, the patient experienced multiple cerebral infarctions during chemotherapy. Subsequently, the patient chose to decline further treatment and was discharged. This exceptional case imparts several noteworthy lessons. First, the coexistence of Mullerian anomalies, although rare, is not incompatible with Turner syndrome. Second, screening for KIT mutations is imperative to reduce the risk of dysgerminoma in Turner syndrome, especially for patients with Y mosaicism who are recommended for hormone replacement therapy. Lastly, comprehensive anticoagulation therapy is crucial for Turner syndrome patients undergoing cisplatin-based chemotherapy.

Application of hysteroscopy in female fertility preservation. / å®«è ”é•œåœ¨å¥³æ€§ç”Ÿè‚²åŠ›ä¿æŠ¤ä¸­çš„åº”ç”¨.

Under the background of the trend in late marriage and the relaxation of family planning policy, the reproductive behavior of women has changed and the proportion of elderly pregnant women has increased progressively year by year. Thus the female fertility preservation is particularly important. As the cradle of life, uterine malformation and uterine cavity diseases may have adverse effects on embryo implantation and development. Several common intrauterine diseases, such as uterine submucosal fibroids, endometrial polyps, intrauterine adhesions, uterine malformation, cesarean scar diverticulum, and embryo residues, may affect female fertility. Hysteroscopy is the gold standard for the diagnosis and treatment for intrauterine diseases. With the progress in science and technology, the refinement of hysteroscopy instruments and the promotion of transvaginal endoscopic technology, hysteroscopy will yield brilliant results in female fertility preservation. The knowledge and training related to hysteroscopy should be continuously promoted and popularized, so that it can be mastered by more clinicians and applied in clinical practice to benefit more female patients.

Molecular Dietary Analysis of Three Sympatric Mustelidae in Northeast China.

Diet analysis is essential to fully understand the biology of a species and its function within the ecosystem, as well as being key in identifying food web interactions and the population dynamics of predators and prey. The understanding of the diet of small to mid-sized carnivores remains generally lacking or uninformative due to the inability for taxonomic resolution based on morphology. The yellow-throated marten (Martes flavigula), Eurasian river otter (Lutra lutra), and Siberian weasel (Mustela sibirica) are three important Mustelidae species in ecosystems of northeast China. Based on fecal DNA and a next-generation sequencing (NGS) approach, we analyzed the vertebrate prey of these three sympatric Mustelidae. Prey included 7 mammalian taxa, 10 fishes, 2 birds, and 2 amphibians, with 85% of the taxa assigned to the species level. In total, twenty-one vertebrate prey taxa were identified from seven yellow-throated martens, eight Eurasian river otters, and two Siberian weasels. Concerning identified dietary species, 10 taxa were consumed by yellow-throated martens, 14 by Eurasian river otters, and 4 by Siberian weasels. Some prey species were identified in more than one species. Amphibians and fishes were the most dominant Eurasian river otter prey categories, whereas Eurasian badger (Meles leucurus), birds, and rodents were the main yellow-throated marten prey; amphibians and rodents were largely contained in Siberian weasel prey. Among prey items, Dybowski's frog (Rana dybowskii) and Korean field mouse (Apodemus peninsulae) were identified in all three Mustelidae species but our analyses suggest potential diet preferences among Mustelidae species. Future studies should focus on understanding the trophic relationships of these three Mustelidae species, providing valuable information for their conservation planning.

Relationship between Vitamin D Level and Subclinical Hypothyroidism in Patients with Gestational Diabetes Mellitus.

BACKGROUND: The aim was to investigate the relationship between the vitamin D (VitD) level and the incidence rate of subclinical hypothyroidism in patients with gestational diabetes mellitus (GDM) in early pregnancy. METHODS: Ninety eligible patients who underwent physical examination from March 2015 to September 2017 were selected. The levels of serum 25-hydroxyvitamin D (25-OH-VD), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured. The correlations of VitD level with those of thyroid function-related indices were analyzed. RESULTS: The serum 25-OH-VD level was (17.82 ± 3.45) ng/mL in the 90 GDM patients in early pregnancy, including 64.44% patients in VitD deficiency group, 22.22% patients in VitD insufficiency group, and 13.33% in VitD sufficiency group. No significant differences in the levels of serum FT4, FT3, and TSH were found among different VitD groups (p > 0.05), but the level of TPOAb gradually decreased (p < 0.05). There was no significant difference in the incidence rate of subclinical hypothyroidism among different VitD groups (p > 0.05). VitD level was not correlated with those of FT4, FT3, and TSH (p > 0.05), but negatively correlated with that of TPOAb (p < 0.05). An increase of TPOAb level raised the risk of VitD deficiency in pregnant women (p < 0.05). Patients suffered from significant 25-OH-VD deficiency in spring and winter (p < 0.05). CONCLUSIONS: GDM patients in early pregnancy display VitD deficiency, and their serum 25-OH-VD level is affected by seasons and not significantly related to subclinical hypothyroidism. However, the increased level of TPOAb may raise the risk of VitD deficiency in pregnant women.

Animal Detection and Classification from Camera Trap Images Using Different Mainstream Object Detection Architectures.

Camera traps are widely used in wildlife surveys and biodiversity monitoring. Depending on its triggering mechanism, a large number of images or videos are sometimes accumulated. Some literature has proposed the application of deep learning techniques to automatically identify wildlife in camera trap imagery, which can significantly reduce manual work and speed up analysis processes. However, there are few studies validating and comparing the applicability of different models for object detection in real field monitoring scenarios. In this study, we firstly constructed a wildlife image dataset of the Northeast Tiger and Leopard National Park (NTLNP dataset). Furthermore, we evaluated the recognition performance of three currently mainstream object detection architectures and compared the performance of training models on day and night data separately versus together. In this experiment, we selected YOLOv5 series models (anchor-based one-stage), Cascade R-CNN under feature extractor HRNet32 (anchor-based two-stage), and FCOS under feature extractors ResNet50 and ResNet101 (anchor-free one-stage). The experimental results showed that performance of the object detection models of the day-night joint training is satisfying. Specifically, the average result of our models was 0.98 mAP (mean average precision) in the animal image detection and 88% accuracy in the animal video classification. One-stage YOLOv5m achieved the best recognition accuracy. With the help of AI technology, ecologists can extract information from masses of imagery potentially quickly and efficiently, saving much time.

LncRNA FGD5-AS1 drives the malignant development of gastric cancer by negatively interacting with FZD3.

We aimed to detect the expression pattern of long non-coding RNA (lncRNA) FGD5-AS1 in gastric cancer (GC) samples and its impact on driving the development of GC. FGD5-AS1 levels in 66 cases of GC tissues and paracancerous ones were detected. Its influences on clinical features and prognosis in GC patients were analyzed. In AGS and SGC-7901 cells with FGD5-AS1 knockdown, phenotype changes were assessed through cell counting kit-8 (CCK-8), Transwell and wound healing assay. The downstream target of FGD5-AS1 was searched by a bioinformatics tool and confirmed by dual-luciferase reporter assay. Their interaction in regulating the malignant development of GC was finally explored. FGD5-AS1 was upregulated in GC tissues compared to paracancerous ones. GC patients expressing a high level of FGD5-AS1 had higher risk of lymphatic metastasis or distant metastasis and worse prognosis than those with a low level. Knockdown of FGD5-AS1 weakened proliferative and metastatic abilities in AGS and SGC-7901 cells. FZD3 was the downstream target of FGD5-AS1. Protein levels of FZD3 and FZD5 were upregulated, while b-catenin, TGF-b and MMP9 were downregulated in GC cells with FGD5-AS1 knockdown. Knockdown of FZD3 abolished the regulatory effects of FGD5-AS1 on malignant phenotypes of GC cells. FGD5-AS1 is upregulated in GC samples, which is linked to metastasis and prognosis in GC. It drives proliferative and metastatic abilities in GC cells via negatively interacting with FZD3.

Staples versus subcuticular suture for cesarean skin closure in obese women: A systematic review and meta-analysis.

AIM: Cesarean section (CS) in obese women poses many surgical, anesthetic, and logistical challenges. This systematic review and meta-analysis aimed to compare the outcomes between staples versus subcuticular suture for cesarean skin closure in obese women undergoing CS. METHODS: PubMed, EMBASE and CENTRAL databases were searched for relevant articles using the keywords cesarean section, cesarean delivery, staple, suture, closure and obese. Randomized controlled trials (RCTs), prospective and retrospective studies comparing between staples and subcuticular suture for wound closure in obese women (BMI ≧ 30 kg/m2) were eligible for inclusion. Outcomes were composite wound complication, wound separation, infection and wound appearance satisfaction. RESULTS: Four studies (two RCTs, one retrospective, one post hoc analysis of an RCT) met the inclusion criteria, with a total of 2,038 obese women undergoing CS, of whom 984 had wound closure by staples and 1,054 had wound closure by subcuticular suture. Pooled analysis did not show significant differences on the risk for composite wound complication, infection, wound appearance satisfaction score or wound separation between staples and sutures. CONCLUSIONS: In obese women receiving CS, it appears there are no significant differences in wound complication, infection, satisfaction scores or wound separation between staples and subcuticular suture. These findings may help optimize risk stratification for obese CS patients. A larger study size meta-analysis is needed to confirm the findings.

Recognition of Coat Pattern Variation and Broken Tail Phenomenon in the Asiatic Golden Cat (Catopuma temminckii).

The Asian golden cat (Catopuma temminckii) is the most varied wild cat species in terms of coat color. Understanding coat pattern variation will help to elucidate the mechanisms behind it as well as its relationship with the environment. We conducted long-term (2013-2021) monitoring of Asian golden cats in the Yarlung Zangbo Grand Canyon National Nature Reserve, Tibet, using camera traps at 283 points over 89,991 camera days. A total of 620 cat photos were recorded, including 344 (55.48%) with recognizable color patterns. Vector graphics of the coat patterns were extracted from the field image data, which revealed 10 color types in the ratio common: cinnamon: reddish-brown long hair: ocelot: blackening: melanistic: gray: brown: brown short hair: pure black = 123:76:57:35:22:8:7:7:5:4. The genes for coat pattern variation are widespread in the Asian golden cat population and are relatively stable. The increase in population size intraspecific competition has led to the tail break phenotype in individual cats. The gene encoding for tail breakage in Asian golden cats remains unknown. This study provides basic information for understanding faunal diversity in the Eastern Himalayan biodiversity hotspot and serves as a reference for studies on the formation mechanisms for feline color pattern diversity.

Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth.

Tumors can reprogram the functions of metabolic enzymes to fuel malignant growth; however, beyond their conventional functions, key metabolic enzymes have not been found to directly govern cell mitosis. Here, we report that glutamine synthetase (GS) promotes cell proliferation by licensing mitotic progression independently of its metabolic function. GS depletion, but not impairment of its enzymatic activity, results in mitotic arrest and multinucleation across multiple lung and liver cancer cell lines, patient-derived organoids and xenografted tumors. Mechanistically, GS directly interacts with the nuclear pore protein NUP88 to prevent its binding to CDC20. Such interaction licenses activation of the CDC20-mediated anaphase-promoting complex or cyclosome to ensure proper metaphase-to-anaphase transition. In addition, GS is overexpressed in human non-small cell lung cancer and its depletion reduces tumor growth in mice and increases the efficacy of microtubule-targeted chemotherapy. Our findings highlight a moonlighting function of GS in governing mitosis and illustrate how an essential metabolic enzyme promotes cell proliferation and tumor development, beyond its main metabolic function.

Study on the Influence of Shear Stress and Pulse Electrical Stimulation to the Growth of Cardiomyocytes.

Engineered myocardial tissue is expected to be used in the treatment of myocardial defects and other diseases, and one of the keys is to construct a suitable environment for the culture of myocardial tissue in vitro. In this study, flow shear stress and pulse electrical stimulation were applied to cardiomyocytes with a self-designed device by simulating the mechanical and electrical physiological microenvironment of myocardial tissue. The strength and duration of pulse electrical stimulation as well as the intensity of shear stress were studied in detail to optimize the experimental parameters. Concretely, 100 mV pulse electrical stimulation (1 Hz and 10 ms pulse width) and 10 dyn/cm² shear stress were used for studying the influence of combined mechanical-electrical stimulation to the growth of cardiomyocytes. The mechanical factor of the combined stimulation promoted the expression of α-cardiac actin mRNA, the electrical factor caused an increase in Cx-43 mRNA expression, and shear stress and pulse electrical stimulation showed a synergistic action on the expression of GATA-4 mRNA. It indicated that combined mechanical-electrical stimulation had a better effect on the functionalized culture of cardiomyocytes, which provided an important theoretical basis for the further construction of in vitro engineered myocardial tissue.

Symptoms associated with nucleic acid turning-negative-time in COVID-19 patients?

To explore on the association between nucleic acid turning-negative-time and traditional Chinese medicine (TCM) symptoms in coronavirus disease 2019 (COVID-19) patients with the Omicron variant. Method: For this retrospective cross-sectional study, we enrolled 189 patients with COVID-19 (age 20-90 years) were included. multiple linear regression models were used to investigate the TCM symptoms affecting the nucleic acid turning-negative-time of COVID-19 patients, during the process of data analysis, taking with nucleic acid turning-negative-time as the dependent variable, and TCM symptoms as independent variables, and at the same time, sex, age, hypertension, diabetes, and coronary heart disease were as confounding variables. Results: The study found that the most common TCM symptoms of COVID-19 patients with Omicron were cough, dry throat, expectoration, fever, sore throat, pharyngeal itching, running nose, and nasal congestion. Regression analysis showed that the fit regressive equation showed a significant difference (F = 4.286, P < 0.001), R = 0.400, the adjusted R 2 = 0.123, and three variables in the regression equation showed significant difference (P < 0. 05). The results showed that nucleic acid turning-negative-time was mostly related to constipation, fever, and expectoration. If the patients had the symptoms of constipation, fever, and expectoration; that is, if patients showed these symptoms, the turning-negative-time of nucleic acid in patients with Omicron will be prolonged. Conclusions: Treatment based on symptoms for patients with constipation, fever, and expectoration may have important clinical significance for the COVID-19 patients with Omicron.