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Low-grade wind with airspeed Vwind < 5 m/s, while distributed far more abundantly, is still challenging to extract because current turbine-based technologies require particular geography (e.g., wide-open land or off-shore regions) with year-round Vwind > 5 m/s to effectively rotate the blades. Here, we report that low-speed airflow can sensitively enable directional flow within nanowire-anchored ionic liquid (IL) drops. Specifically, wind-induced air/liquid friction continuously raises directional leeward fluid transport in the upper portion, whereas three-phase contact line (TCL) pinning blocks further movement of IL. To remove excessive accumulation of IL near TCL, fluid dives, and headwind flow forms in the lower portion, as confirmed by microscope observation. Such stratified circulating flow within single drop can generate voltage output up to ~0.84 V, which we further scale up to ~60 V using drop "wind farms". Our results demonstrate a technology to tap the widespread low-grade wind as a reliable energy resource. [ABSTRACT FROM AUTHOR]

Background Bigu is a health-preserving regimen with a long history advocating appropriately reducing food intake in China, whose efficacy has been confirmed in practical treatment of some diseases currently. However, the applicability of Bigu in human experiments is poor due to nonforcible control of dietary intake in the participants. Objective To assess the effect of medicine-qi intake type of Bigu in healthy people using real-world data. Methods Two hundred and eighty healthy volunteers were recruited from Sichuan Nursing Vocational College from November 2018 to September 2020, and equally divided into two groups (A and B, with 140 cases in each) after being matched using k-nearest neighbor propensity score approach based on their demographics, and received a two-round Bigu trial: in the first round, group A received 10-day diet-restriction type of Bigu, while group B received 10-day medicine-qi intake in combination with diet-restriction type of Bigu. Then, after one-month washout period, the second round was conducted, during which group A received 10-day medicine-qi intake in combination with diet-restriction type of Bigu, while group B received 10-day diet-restriction type of Bigu. Comparisons were performed between two groups in terms of incidence of adverse reactions and number of dropouts in two rounds of Bigu, and subjective hunger sensation, weight, BMI, morning blood pressure, and fasting fingerstick glucose on the first and 10th days of two rounds of Bigu. Results After being assigned by PSM, there were 72 males and 80 females in group A; 61 males and 67 females in group B. In the first round, the incidence of adverse reactions in group A was 65.7% (92/140) , and the trial discontinuation rate was 48.6% (68/140) ; the incidence of adverse reactions in group B was 42.9% (60/140) , and the trial discontinuation rate was 20.0% (28/140) . The incidence of adverse reactions and trial discontinuation rate in group A were higher than those in group B, and the difference was statistically significant (P

Slime mould algorithm (SMA) and arithmetic optimization algorithm (AOA) are new meta-heuristic optimization algorithms proposed recently. SMA has strong ability of global exploration, but the oscillation effect is weak in the late iteration. It is easy to fall into local optimum, and the contraction mechanism is not strong, which leads to slow convergence speed. AOA algorithm uses multiplication and division operator to update position, which has strong randomness and good ability to avoid premature convergence. To solve the above problems, this paper combines the two algorithms and uses random opposition-based learning strategy to improve the convergence speed, and proposes a hybrid algorithm of slime mould algorithm and arithmetic optimization algorithm based on random opposition-based learning (HSMAAOA) with superior performance and high efficiency. The improved algorithm retains the SMA’s exploration phase and the exploitation phase will be replaced by the multiplication and division operators, which improves the capacity of the algorithm and the ability to jump out of the local optimal solution. In addition, random opposition-based learning strategy is used to enhance the diversity of the improved algorithm population and improve the convergence speed. The experimental results show that the HSMAAOA algorithm has good robustness and optimization accuracy, and significantly improves the convergence speed. Finally, the applicability and effectiveness of HSMAAOA in engineering problems are verified through the design of welded beams and the design of pressure vessels.

Abstract Receptor interacting serine/threonine protein kinase 1 (RIPK1) activation and necroptosis have been genetically and mechanistically linked with human multiple sclerosis and neurodegenerative diseases for which demyelination is a common key pathology. Demyelination can be healed through remyelination which is mediated by new oligodendrocytes derived from the adult oligodendrocyte progenitor cells (OPCs). Unfortunately, the efficiency of remyelination declines with progressive aging partially due to the depletion of OPCs following chronic or repeated demyelination. However, to our knowledge, so far there is no drug which enhances proliferation of OPCs, and it is unknown whether inhibiting RIPK1 activity directly affect OPCs, the central player of remyelination. Using TNFα induced RIPK1-dependent necroptosis in Jurkat FADD−/− cells as a cell death assay, we screened from 2112 FDA-approved drugs and the drug candidates of new RIPK1 inhibitors selected by ourselves, and identified ZJU-37, a small molecule modified by introducing an amide bond to Nec-1s, is a new RIPK1 kinase inhibitor with higher potency than Nec-1s which has the best reported potency. We unveil in addition to protecting myelin from demyelination and axons from degeneration, ZJU-37 exhibits a new role on promoting proliferation of OPCs and enhancing remyelination by inhibiting RIPK1 kinase activity with higher potency than Nec-1s. Mechanistically, ZJU-37 promotes proliferation of OPCs by enhancing the transcription of platelet derived growth factor receptor alpha via NF-κB pathway. This work identifies ZJU-37 as a new drug candidate which enhances remyelination by promoting proliferation of OPCs, paving the way for a potential drug to enhance myelin repair.

Abstract SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

Age-dependent decline in remyelination in the CNS is associated with declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). Here, the authors show nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing in mouse OPCs. β-nicotinamide mononucleotide (β-NMN) supplement delays myelin aging and enhances remyelination in the aged mice.

Abstract Background ITPR1 is a key gene for autophagy, but its biological function is still unclear, and there are few studies on the correlation between ITPR1 gene expression and the occurrence and development of breast cancer. Methods Analyze the expression of ITPR1 through online databases such as Oncomine and TIMER. Kaplan–Meier plotter and other databases were used to evaluate the impact of ITPR1 on clinical prognosis. The expression of ITPR1 in analysis of 145 cases of breast cancer and 30 cases of adjacent normal tissue was detected by Immunohistochemistry. Statistical analysis was used to evaluate the clinical relevance and prognostic significance of abnormally expressed proteins. And the Western Blot was used to detect the expression of ITPR1 between breast cancer tissues and cells. The TIMER database studied the relationship between ITPR1 and cancer immune infiltration. And used the ROC plotter database to predict the response of ITPR1 to chemotherapy, endocrine therapy and anti-HER2 therapy in patients with breast cancer. Results Compared with normal breast samples, ITPR1 was significantly lower in patients with breast cancer. And the increased expression of ITPR1 mRNA was closely related to longer overall survival (OS), distant metastasis free survival (DMFS), disease specific survival (DSS) and relapse free survival (RFS) in breast cancer. And the expression level of ITPR1 was higher in patients treated with chemotherapy than untreated patients. In addition, the expression of ITPR1 was positively correlated with related gene markers of immune cells in different types of breast cancer, especially with BRCA basal tissue breast cancer. Conclusion ITPR1 was lower expressed in breast cancer. The higher expression of ITPR1 suggested favorable prognosis for patients. ITPR1 was related to the level of immune infiltration, especially in BRCA-Basal patients. All research results indicated that ITPR1 might affect breast cancer prognosis and participate in immune regulation. In short, ITPR1 might be a potential target for breast cancer therapy.

Bile duct hamartomas (BDHs), also known as von Meyenburg complexes, are small neoplasms of the liver, of which the pathology is a benign bile duct malformation. We report a case of multiple BDHs of a 55-year-old male diagnosed using two-dimensional (2-D) ultrasound combined with contrast-enhanced ultrasound (CEUS) and further clinically diagnosed using magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP). The 2-D ultrasound showed diffusely distributed hyperechoic nodules and cystic masses in the liver, accompanied by small strong echoes with a comet tail sign. The CEUS showed that the hyperechoic nodules observed no abnormal enhancement in the arterial phase and equal enhancement with the surrounding liver tissue in the portal vein and delayed phase. We conclude that the appearance of BDHs on ultrasound has distinct characteristics and can be used as the preferred method for diagnosis. The CEUS can differentially diagnose the disease and improve diagnostic accuracy. Therefore, 2-D ultrasound, combined with CEUS, is a helpful method for diagnosing BDHs.

Spiribacter is the most abundant bacterial genus in the intermediate-salinity zones of hypersaline environments. However, Spiribacter strains are extremely difficult to isolate in pure culture. Therefore, the characteristics, genome features, and adaption mechanisms that allow Spiribacter strains to thrive in highly saline conditions are largely unknown. Here, we show that Spiribacter is predominant in brines from marine solar salterns and sulfate-type salt lakes with intermediate to saturated salinities. Using a high-salt medium, we isolated a novel strain, Spiribacter halobius E85T, which possesses a relatively large and distinct genome. The genome of strain E85T has a length of 4.17 Mbp, twice that of other Spiribacter species genomes and the largest described genome within the family Ectothiorhodospiraceae. Comparative genomic analyses indicate that approximately 50% of E85T genes are strain-specific, endowing functional differences in its metabolic capabilities, biosynthesis of compatible solutes, and transport and pumping of solutes into the cell from the environment. Hundreds of insertion sequences result in many pseudogenes and frequent gene fragment rearrangements in the E85T genome. Dozens of genomic islands, which show a significant preference for replication, recombination and repair, and cell motility and may have been gained from other bacterial species, are scattered in the genome. This study provides important insights into the general genetic basis for the abundance of Spiribacter in hypersaline environments and the strain-specific genome evolutionary strategies of strain E85T.

The article presents a case study of a 20-year-old male patient with pulmonary artery dissection secondary to a ventricular septal defect and pulmonary valve stenosis. Topics discussed include diagnostic imaging techniques, the pathological features of pulmonary artery dissection, and the importance of early surgical intervention.

In this study, graphene oxide (GO) was prepared by the improved Hummers method, and a synergistically stabilized emulsion of GO and emulsifier was formulated. The best emulsion formula obtained by Response Surface Methodology consists of 1.39? GO, and 2.92? OP-10; the water-oil ratio is 4:6, achieving an emulsion index of 92.83%. The emulsion still maintained good stability under high temperature and high salt conditions, meeting the environmental requirements of medium and low permeability reservoirs. For injected water flooding, emulsion flooding could increase the oil recovery by 15.41%. [ABSTRACT FROM AUTHOR]

The landslide disaster caused huge losses to human lives and property, and the research on the selection of landslide treatment schemes has attracted global attention. Fuzzy multiattribute decision-making methods are widely used for selecting the slope treatment schemes in engineering practice. But they do not take into account human linguistic arguments in the linguistic decision-making environment, which usually contains incomplete and uncertain information, and still lack a qualitative evaluation method. To deal with multiple attribute group decision-making (MAGDM) problems of landslide treatment schemes in the linguistic neutrosophic environment, a linguistic neutrosophic number Dombi weighted arithmetic averaging (LNNDWAA) operator and a linguistic neutrosophic number Dombi weighted geometric averaging (LNNDWGA) operator are developed to aggregate linguistic neutrosophic information. Then, a new MAGDM method using these aggregation operators is proposed in view of the Dombi operational flexibility. Finally, the proposed method is applied to select the optimal landslide treatment scheme under the linguistic neutrosophic environment. The results show that this method can effectively solve the decision-making problem of landslide treatment schemes and make the decision result more reasonable and flexible than other existing methods. [ABSTRACT FROM AUTHOR]

When a circular tube is under axial compression, it can be developed into specific forming technologies (e.g., tube inversion). However buckling failure is prone to occurring and seriously restricts the successful realization of the forming process or service performance. In this paper the conical convex or concave dies with different semi-cone angles were adopted to change tube end contact conditions and the buckling process, critical buckling force and the buckling waves of AA6061 tube under axial compression were investigated by using finite element simulation combined with experiments. The results show that the buckling deformation, the position where initial buckling wave appears, and the distribution of axial stress in tube blank are quite different when axially compressed on a flat die or a conical convex die (semi-cone angle β = 60°). For the conical convex dies as semi-cone angle increases from 75° to 87.5°, or for concave dies as semi-cone angle decreases from 110° to 92.5°, the axial compressive stress, critical buckling force and critical reduction increase, while the peak of the buckled wave decreases, i.e., occurrence of buckling delays and the buckling becomes more difficult to occur. When β is 90° (flat die), the critical buckling force and reduction reach the peak values.

Abstract. Endometriosis is a prevalent chronic disease that affects approximately 6% to 10% of reproductive-aged women. Although numerous researchers have endeavored to explore the etiology of endometriosis over a century, its etiology still remains an enigma. The exploration of pathophysiologic mechanism and novel therapy for endometriosis depends on ideal endometriotic models. In the previous decade, various endometriotic models have been established; therefore, we made a conclusion for available information on these models. This review summarized the common experimental models used in endometriotic studies, including their origins, characteristics, applications, and limitations. Endometriotic models played an important role in studying etiologies and novel treatments of endometriosis during the last decades. Among them, animal models and endometriotic cell lines were viewed as most common studying tools to explore the intrinsic entities of endometriosis. In addition, endometrial organoid also emerged and was regarded as an ideal studying tool for endometriosis research. Different research models collectively complement each other to advance the endometriosis research. The successful establishment of endometrial organoids means that organoids are expected to become an ideal model for studying endometriosis in the future.

Examines the significance of tissue-selective TATA binding protein-associated factor in ovarian development in mice. Correlation between infertility and lack of TAF[sub II]105; Identification of a defective inhibin-activin signaling pathway in TAF[sub II]105-deficient disorders; Role of TAF[sub II]105 in mediating gene transcription.

PurposeTriple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC.MethodsCorrelation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity in vivo.ResultsPTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression in vivo.ConclusionThis study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression via EGFR/Akt signaling pathway.

Abstract Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is a new promising target for the treatment of ovarian cancer. Our previous study showed that cross‐reacting material 197 (CRM197), a specific HB‐EGF inhibitor, significantly reverses resistance against paclitaxel in paclitaxel‐resistant ovarian cancer cells. However, the mechanism of the effect of CRM197 on the reversion of paclitaxel resistance was unclear. In this study, in vitro and in vivo data suggested that CRM197 treatment sensitized paclitaxel‐resistant ovarian cancer cells to paclitaxel, at least in part, via nucleus accumbens‐1 (NAC‐1) and its downstream pathway, DNA damage‐inducible 45‐γ interacting protein (Gadd45gip1)/growth arrest and DNA damage‐inducible 45 (Gadd45), in A2780/Taxol and SKOV3/Taxol cells. The results also showed that CRM197 activated the proapoptotic JNK/p38MAPK pathway to enhance caspase‐3 activity and apoptosis by downregulation of the NAC‐1/Gadd45gip1/Gadd45 pathway, leading to reversion of paclitaxel resistance in A2780/Taxol and SKOV3/Taxol cells. This study provides the first mechanism through which CRM197 significantly reverses resistance against paclitaxel by modulating the NAC‐1/Gadd45gip1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells, and the mechanism of HB‐EGF inhibition as a novel therapeutic strategy for patients with paclitaxel‐resistant ovarian cancer.

Abstract Objective To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. Methods This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. Results The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615–0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054–1.190, p

Abstract Background Atrial fibrillation (AF) is a common complication after radical surgery of esophageal cancer. The aim of this study was to explore AF risk factors after radical surgery of esophageal carcinoma. Method The data of 335 patients with esophageal cancer who were admitted in our hospital from January 2014 to August 2016 for the first time were retrospectively analyzed. We retrieved the papers in some data banks using the search terms including English and Chinese search terms, and obtained 13 factors which were mentioned in more than 6 papers. The 13 factors including age, gender, history of smoking, history of hypertension, history of peripheral vascular disease, history of cardiac stents or angina pectoris, preoperative pulmonary infection, preoperative brain natriuretic peptide (BNP) level, preoperative left ventricular diastolic dysfunction, operative method, lesion location, intraoperative blood transfusion, adhesion between lymph nodes and pericardium, underwent univariate and multivariate analyses. Results Of the 335 patients with esophageal cancer, 48 had AF within one week after operation. Univariate analysis indicated that the age (OR: 4.89; CI: 2.53–9.47, P: 0.000), gender (OR: 2.26; CI: 1.17–4.37, P: 0.013), history of peripheral vascular disease (OR: 2.29; CI: 1.06–4.92, P: 0.030), history of cardiac stents or angina pectoris (OR: 27.30; CI: 12.44–59.91, P: 0.000), preoperative BNP level (OR: 27.13; CI: 10.97–67.06, P: 0.000), preoperative left ventricular diastolic dysfunction (OR: 2.22; CI: 1.19–4.14, P: 0.012), operative method (OR: 2.09; CI: 1.002–4.380, P: 0.046), intraoperative blood transfusion (OR: 20.24; CI: 8.39–48.82, P: 0.000), and adhesion between lymph nodes and pericardium were risk factors (OR: 2.05; CI: 1.08–3.87, P: 0.024). Furthermore, multivariate analysis displayed that advanced age (OR: 5.044; CI: 1.748–14.554, P: 0.003), male (OR: 6.161; CI: 2.143–17.715, P: 0.001), history of cardiac stents or angina pectoris (OR: 48.813; CI: 13.674–174.246, P: 0.000), preoperative BNP > 100 (OR: 41.515; CI: 9.380–183.732, P: 0.000), open surgery (OR: 3.357; CI: 1.026–10.983, P: 0.045), intraoperative blood transfusion (OR: 58.404; CI: 10.777–316.509, P: 0.000), and adhesion between lymph nodes and pericardium (OR: 3.954; CI: 1.364–11.459, P: 0.011) were risk factors which could increase the incidence of postoperative AF. Conclusion We should pay attention to the above risk factors in order to reduce the incidence of postoperative AF.

ABSTRACTDromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor-binding domain positive (RBD) of spike protein positive camel sera in Kenya were also seropositive to MERS-CoV nucleocapsid (NP). In contrast, many of them contain antibodies against bat HKU8-related (HKU8r)-CoVs. Among 584 camel samples that were positive against MERS-CoV RBD, we found only 0.48 (8.22%) samples were also positive for NP. Furthermore, we found bat HKU8r-CoV NP antibody in 73 (12.5%) of the MERS-CoV RBD positive and NP negative samples, yet found only 3 (0.43%) of the HKU8r-CoV S1 antibody in the same samples. These findings may indicate co-infection with MERS-CoV and a HKU8r-CoV in camels. It may also raise the possibility of the circulation of a recombinant coronavirus virus with the spike of MERS-CoV and the NP of a HKU8r-CoV in Kenya. We failed to find molecular evidence of an HKU8r-CoV or a putative recombinant virus. Our findings should alert other investigators to look for molecular evidence of HKU8r-CoV or recombinants.

Abstract Background Because of the rarity of endometrioid borderline ovarian tumours (EBOTs), there is a paucity of data concerning the natural history and prognosis of this condition. Thus, the objective of our study was to establish the feasibility of fertility preservation in young women with EBOTs, as well as their oncological and reproductive outcomes. Methods Consecutive patients with EBOTs, treated at a tertiary referral centre during a span of 22 years, were retrospectively analysed. Recurrence-free interval, as well as its association with the type of surgery and with other clinical and pathological features, was assessed using the Kaplan-Meier and Cox proportional hazards methods. Results Of the 59 patients studied, the median follow-up time was 30 months (range, 6–177 months). Nine (15.3%) patients developed 13 recurrences 6–137 months after the initial surgeries, including three patients (5.1%; n = 3/59) who developed six invasive recurrences 8, 18 and 68 months after their initial surgeries. Conservative surgery showed a tendency towards a high recurrence rate (17.2% versus 13.3%); however, this difference was not significant (p = 0.45). The 5-year recurrence-free survival rate was significantly higher in the oophorectomy group than in the cystectomy group (p = 0.001). Cox regression analysis showed that none of the variables assessed were associated with an increased hazard ratio for recurrence, except for a younger age at diagnosis (p = 0.021). Of 20 patients who attempted to conceive, three pregnancies among two patients (10.0%) resulted in two live births. Conclusions Conservative surgery with unilateral adnexectomy can be proposed for young women with EBOTs with fertility desire; however, the reproductive result is not satisfactory. In addition, careful evaluations of the endometria should be offered during the initial surgery and follow-up period. Trial registration Retrospectively registered.

Abstract Background Synchronous endometrial disorders have been poorly studied in women with endometrioid borderline ovarian tumors (EBOT). The aims of this study were to investigate the risk of endometrial disorders among women with EBOT and associated factors, as well as their oncological and fertility outcomes. Results This retrospective study included 33 women with EBOT. Their mean age was 41.9 years, and endometria were evaluated in 25 of these patients. The prevalence of synchronous endometrial disorders was 52.0% (n = 13/25) and this incidence was 41.4% (n = 46/111) after systematic analysis. Univariable analysis showed that EBOT patients who were younger, nulliparous, and had experienced abnormal vaginal bleeding were more likely to have synchronous endometrial disorders. The median follow-up was 54 months (range: 14-250 months), and three patients (10.3%) developed recurrences. No deaths due to EBOT were recorded. Among the nine nulliparous women treated conservatively who were attempting to conceive, only one (11.1%) pregnancy resulted in a live birth. Conclusions Synchronous endometrial disorders are common in women with EBOT, especially in those who are younger, nulliparous, and have experienced abnormal vaginal bleeding. Thus, endometrial sampling should be performed in women with EBOT undergoing conservative surgery, and a hysterectomy should be performed in cases requiring radical treatment.

Background: Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment. Methods: A total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions. Results: Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752–0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571–0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network. Conclusions: This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.

The majority of emerging and reemerging zoonotic viral pathogens are RNA viruses. Pathogen discovery programs of emerging infectious diseases (EIDs) in wildlife have implicated rodents and shrews as hosts of diverse human pathogens, such as hantaviruses, arenaviruses, paramyxoviruses, etc. Despite these threats, little is known about the diversity of viruses circulating among rodents and shrews in Kenya, meaning the risk of infectious disease outbreak from these small mammals could be oblivious. This study reports the first surveillance toward understanding the diversity of RNA viruses carried by rodents and shrews in areas of high-potential contact with humans in Kenya through molecular detection. A total of 617 samples comprising fecal, urine, and tissues from 138 rodents and 5 shrews were screened for eight different families of viruses using RT-PCR assays. The results highlight the presence of diverse astroviruses, paramyxoviruses, hepeviruses, and arenavirus, circulating in both wild and synanthropic Kenyan rodents and shrews. Most of the viruses detected in this study are novel strains and some belong to the families that contain important human viral pathogens. Notably, a novel arenavirus was detected in Grammomys macmillani, a rodent species newly identified to harbor arenavirus, and it potentially represent a novel arenavirus species. Our findings demonstrate the need for continued pathogen surveillance among these small mammals as well as among the vulnerable and exposed livestock and humans. This would help in development and implementation of effective preventive and control strategies on EIDs in countries with rich wildlife biodiversity like Kenya.

Programmed cell death (PCD) plays a critical role in the development of plant pigment glands, while H2O2, which is a kind of reactive oxygen species (ROS) produced by the aerobic metabolism of cells, acts as an important signal in this process. Here, we investigated the temporal and spatial dynamics of accumulated H2O2 in pigment glands of Gossypium hirsutum L. with 3,3-diaminobenzidine (DAB) staining, 2',7'-dichlorodihydrofluorescein diacetate (DCFH2)-DA fluorescent labeling and CeCl3 cytochemical localization techniques. The results showed that the pigment glands of G. hirsutum could generate H2O2, and the amount and localization of H2O2 varied at different developmental stages. At the early developmental stage, a small amount of H2O2 accumulated in the vacuole membrane of pigment gland cells. At the intermediate stage, a large number of H2O2 appeared in the vacuole membrane, while cell walls started to accumulate a small amount of H2O2. When pigment gland cell degraded, H2O2 mainly accumulated on the chloroplast envelope membrane of inner sheath cells. With the degradation of the sheath cells, H2O2 was detected in cell wall and the membrane of secretory vesicles which contains the preliminary contents of pigment gland. With the pigment glands completely maturation, H2O2 would disappeared. The accumulation sites of H2O2 are consistent with the process of PCD of individual gland cells, which started from the degradation of intracellular membrane and ended with the degradation of cell walls. Thus H2O2 probably plays an important role in the development of pigment glands. In addition, the development of pigment glands and the generation of H2O2 are not associated with the light, and no H2O2 was detected in the secretions of pigment glands.

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

Abstract: Background: Tumstatin, an angiogenesis inhibitor with anti-tumor activity in mice, is the bioactive NC1 domain of Col IVa3, the potential significance of tumstatin as an endogenous angiogenesis inhibitor in human is not yet completely understood. This study aimed to develop an enzyme-linked immunoassay (ELISA) for tumstatin to accurately measure its concentrations in biological samples. Methods: Recombinant tumstatin as an immunogen was expressed by E. coli. The purified tumstatin was injected into mice for antibody generation. An ELISA was developed with the monoclonal antibodies. Results: The detection limit of the ELISA was 1.4ng/ml, and the intra- and inter- assay CVs were within 10%. Recovery of tumstatin added to sera was 92.7–115%. Patients with metastases had serum tumstatin levels 50% lower than patients without metastases (P =0.039). Tumstatin levels in poorly differentiated tumor tissues were significantly lower than in nontumorous tissues and well-differentiated tumor tissues (P <0.001). Conclusions: The development of a highly sensitive and reliable ELISA method capable of quantifying tumstatin in human serum samples and tissue extracts is reported. This assay for tumstatin in biological samples may be helpful in evaluating the therapeutic and/or prognostic value of tumstatin in cancer patients. [Copyright &y& Elsevier]

Objective: To determine the oncofertility outcomes and prognostic factors in a large series of serous borderline ovarian tumor-micropapillary variant (SBOT-M) with a long-term follow-up., Methods: Consecutive patients with SBOT-Ms treated from two affiliated hospitals of the Chinese Academy of Medical Sciences were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free survival (DFS), and overall survival were analyzed, and outcomes of patients treated with conservative and radical surgery were compared., Results: From 2000 to 2020, 200 patients were identified and followed. After a median follow-up of 68 months, 81 patients relapsed. In the multivariate analyses, younger age at diagnosis and conservative surgery that preserved fertility potential were independently associated with worse DFS ( p = 0.018 and <0.001, respectively). Twenty-three patients experienced invasive recurrence, and seven died of progressive disease. Multivariate analysis showed that nulliparous and advanced FIGO stage were independently adversely associated with lethal recurrence ( p = 0.022 and 0.029, respectively). Only advanced FIGO stage at diagnosis was associated with worse overall survival at univariate analysis ( p = 0.02). Among 61 patients attempting conception, 37 achieved 44 pregnancies and resulted in 32 live births., Conclusions: In this series, patients with SBOT-M have an acceptable oncofertility outcomes. The use of conservative surgery was independently associated with worse DFS, but without an impact on neither invasive relapse nor on overall survival. Patients with advanced FIGO stages had a significantly higher risk of lethal recurrence and worse overall survival, suggesting that adequate staging surgery and intensive postoperative surveillance should be warranted., Competing Interests: All authors have nothing to declare., (Copyright © 2022 Shuang-Zheng Jia et al.)

Endometriosis is a prevalent chronic disease that affects approximately 6% to 10% of reproductive-aged women. Although numerous researchers have endeavored to explore the etiology of endometriosis over a century, its etiology still remains an enigma. The exploration of pathophysiologic mechanism and novel therapy for endometriosis depends on ideal endometriotic models. In the previous decade, various endometriotic models have been established; therefore, we made a conclusion for available information on these models. This review summarized the common experimental models used in endometriotic studies, including their origins, characteristics, applications, and limitations. Endometriotic models played an important role in studying etiologies and novel treatments of endometriosis during the last decades. Among them, animal models and endometriotic cell lines were viewed as most common studying tools to explore the intrinsic entities of endometriosis. In addition, endometrial organoid also emerged and was regarded as an ideal studying tool for endometriosis research. Different research models collectively complement each other to advance the endometriosis research. The successful establishment of endometrial organoids means that organoids are expected to become an ideal model for studying endometriosis in the future.

Introduction: Ovarian endometriosis is the most common type of endometriosis (EM), affecting more than 40% of women with EM. Currently, surgical intervention is still controversial in infertile patients with ovarian endometriosis, especially in those with stage III-IV EM. Very few studies have been done to analyze long-term pregnancy results in patients with endometrioma more than 5 years after surgery. Therefore, the aim of this study was to explore the pregnancy outcomes and the related factors in patients with endometrioma and stage III-IV endometriosis during a long-term follow-up postoperatively., Methods: We collected 347 patients with ovarian endometriosis, which included 59 infertile patients with stage III-IV endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing laparoscopic excision of ovarian endometriomas performed by a single doctor at the Peking Union Medical College Hospital from January 2009 to April 2013., Results: A total of 59 infertile patients were recruited. The mean age was 31.8 ± 3.6 years. The mean size of the endometriomas was 6.8 ± 3.3 cm. Before surgery, dysmenorrhea was present in 88.1% (52/59) of the cases, while chronic pelvic pain was reported in nine cases (15.3%). A total of 20.3% (12/59) of cases were concurrent with leiomyoma, 52.5% (31/59) with deep infiltrating endometriosis (DIE), and 39.0% (23/59) with adenomyosis. During laparoscopy, 21 cases were diagnosed as stage III (35.6%) and 38 as stage IV (64.4%) EM according to the revised American Fertility Society (AFS) classification. After laparoscopic cystectomy, 38 (64.4%) patients became successfully pregnant by the 5th year. All the patients were divided into two groups according to the postoperative pregnancy outcomes. In univariate analysis, the higher mean age and concurrent diagnosis of adenomyosis were seen to be related to poor postoperative pregnancy outcomes (p < 0.05). In multivariate analysis, however, the mean age, chronic pelvic pain (CPP), and adenomyosis were independent risk factors of pregnancy outcomes between the two groups (p < 0.05). With a minimum follow-up of 6 years, 23.7% (14/59) of recurrence was observed in the entire study cohort., Conclusion: Infertile patients with endometrioma and stage III-IV EM may have lower pregnancy rates after laparoscopic cystectomy if they are older and present with CPP and adenomyosis. Our data showed a lower rate of recurrence but a higher rate of pregnancy after surgery.

Study Question: What are the oncofertility outcomes of young women (≤40 years old) with bilateral serous borderline ovarian tumors (SBOTs) after fertility-sparing surgery?, Summary Answer: Fertility preservation with the bilateral ovarian cystectomy procedure is feasible for bilateral SBOTs, with an acceptable oncological outcome and worthwhile pregnancy rates., What Is Known Already: Fertility-sparing approaches are becoming the standard management of young patients with unilateral SBOTs and other borderline histological subtypes. However, there is a paucity of evidence to dictate the best management in bilateral SBOTs., Study Design, Size, Duration: This was a retrospective observational study performed at the Peking Union Medical College Hospital in Beijing, China, between January 1999 and January 2019., Participants/materials, Setting, Methods: Ninety-four women (≤40 years old) with pathologically confirmed bilateral SBOTs were included. Following preoperative counseling, patients self-selected into one of three treatment modalities: bilateral ovarian cystectomy (n = 48), unilateral adnexectomy plus contralateral cystectomy (UAC; n = 31), and radical surgery (n = 15). Univariate and multivariate analyses were used to determine the clinical and pathological features associated with disease-free survival and reproductive outcomes., Main Results and the Role of Chance: During the median follow-up of 64 months (range, 4-243 months), 61 patients (65%) developed relapse, including 3 (20%) in the radical group, 26 (84%) in the UAC group and 32 (67%) in the bilateral cystectomy group. In the multivariate analyses, preoperative CA-125>300 U/mL, fertility preservation and micropapillary pattern were independently associated with adverse disease-free survival (P = 0.001, 0.03 and 0.026, respectively). Fourteen patients (15%) experienced invasive recurrence, and three (3%) died of progressive disease. The micropapillary pattern was significantly associated with invasive evolution risk (P = 0.006). Of the 49 patients who attempted to conceive, 23 (47%) achieved 27 pregnancies (24 spontaneous and three after IVF-ET), resulting in 19 live births. There was no significant difference in disease-free survival (P = 0.13) or pregnancy rate (41 vs. 50%, P = 0.56) between the UAC and bilateral procedures., Limitations, Reasons for Caution: As a retrospective study conducted in a referral center, inherent biases exist. The nonrandom allocation to treatment groups and relatively small number of patients attempt to conceive might limit the statistical power of our findings. Only 41 patients (43.6%) received complete staging during their initial surgeries, so an underestimation bias in terms of the FIGO stage and extraovarian implants might have occurred., Wider Implications of the Findings: The ultraconservative bilateral ovarian cystectomy procedure should be proposed in bilateral SBOTs when technically feasible. Invasive evolution occurs frequently in these women, and intense follow-up and oncofertility counseling are warranted, especially for those with micropapillary patterns., Study Funding/competing Interest(s): No external funding was used for this study. There are no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: To investigate the expression of transforming growth factor (TGF)-β and Smad pathway expressed in adhesion peritoneums in patients with endometriosis (EM)., Methods: From Dec. 2009 to Mar. 2010, 11 patients with EM [including 3 patients treated by gonadotropin releasing hormone agonist (GnRH-a) treatment] underwent laparoscopy surgery in Peking Union Medical College Hospital. In the mean time, 9 patients with benign ovarian tumor without EM and peritoneum adhesion were chosen as control. Peritoneum from lateral peritoneal cavity, adjacent from lesion and grossly normal was obtained during surgery. Microstructure of peritoneums was observed by HE staining and Masson staining. The expression of TGF-β1, TGF-β3, Smad 3 and Smad 7 in peritoneums were measured by immunohistochemistry staining and real-time PCR. The effect of GnRH-a on expressions of these markers were also analyzed., Results: (1) Microstructures of peritoneum: enlargement of nucleus of peritoneal mesothelial cells, thickening of connective tissue, distributive disorder of fiber, increasing numbers of fibroblast and inflammatory cells in EM were significantly different from those in control group. (2) The expression of TGF-β1 and 3 in peritoneum were 0.170 ± 0.020 and 0.110 ± 0.010 in EM group, which were significantly higher than 0.070 ± 0.010 and 0.050 ± 0.020 in control group. TGF-β1 was downregulated to 0.130 ± 0.030 and TGF-β3 was upregulated to 0.490 ± 0.090 by GnRH-a. (3) The expression of Smad 3 and 7 were 0.140 ± 0.020 and 0.110 ± 0.020 in peritoneum in EM group, which were significantly higher than 0.024 ± 0.004 and 0.014 ± 0.007 in control group. GnRH-a could upregualted the expression of smad 7 (0.040 ± 0.020), however, but no significant effect was observed on regulating Smad3 expression., Conclusions: The changes of microstructure and the alteration of TGF-β/Smad expression in peritoneum of endometriosis were observed. GnRH-a could regulate the expression of TGF-β and Smad.

Objectives: To compare operative characteristics, postoperative residue, recurrence, and pregnancy outcome between laparoscopic myomectomy (LM) and transabdominal myomectomy (TAM), and investigate the favourable surgical approach in women with uterine myomas., Methods: From Jan 2008 to Dec 2008, 313 women undergoing LM and 148 women undergoing TAM were studied retrospectively in Peking Union Medical College Hospital. The patients' general information, including the largest diameter, mean numbers and weights of excised myomas, peri-operative characteristics (operating time, blood loss, and hemoglobin decrease), and residue, recurrence of myoma, and pregnancy outcome were compared and analyzed., Results: The largest diameter, mean numbers and mean weight of myomas removed were larger in TAM group [(7.6 ± 3.0) cm, (5.6 ± 5.5), (308 ± 364) g, respectively] than those in LM group [(6.8 ± 2.0) cm, (2.4 ± 2.1), (140 ± 109) g, respectively; P < 0.01]. While the extension of operating time [(89 ± 32) versus (74 ± 35) min], increased blood loss [(239 ± 251) versus (149 ± 252) ml] and hemoglobin decrease [(22 ± 14) versus (15 ± 12) g/L], and longer hospital stay [(6.4 ± 1.6) versus (4.4 ± 1.3) d] were observed in TAM group when compared with those in LM group (P < 0.01). However, the residue rate of LM and TAM was 2.6% versus 1.4% respectively (P = 0.5130); the recurrence rate of LM and TAM was 11.1% versus 12.3% (P > 0.05); the pregnancy rate of LM and TAM was 49.2% versus 9/13 separately, the difference was not statistically significant (P = 0.2330). The number of myomas removed was the significant risk factors associated with recurrence (OR = 2.805, 95%CI: 1.192 - 6.601, P = 0.0180). No uterine rupture occurred during pregnancy., Conclusions: Both LM and TAM are effective surgical approaches for the patients with leiomyoma who desire to pregnancy, or to retain the integrity of their uteruses. Most of uterine myoma could be treated through laparoscopy. The residue rate of LM is higher than that of TAM. However, the short term recurrence rates of LM and TAM are similar. Multiple myomas is the risk factor associated with recurrence after myomectomy. The pregnancy rates are comparable between LM and TAM groups.

Objective: To discuss the failure reasons of operation for spinal tuberculosis complicated with paraplegia and methods of the second operation., Methods: Spinal tuberculosis paraplegic patients (18 males, 14 females) were reviewed retrospectively. They have been treated with failing decompressive surgery from January 2001 to December 2006. Seventeen patients received anterior debridement surgery via transpleural approach while the other 15 patients received posterolateral decompression surgery via costotransverse approach. Twenty-two patients got chemotherapy after the surgery., Results: Twenty-three patients were treated by anterior debridement, decompression and graft placement via transpleural approach (9 received the single-stage posterior instrumentation). Five patients received posterolateral debridement and decompression via extrapleural approach. Two patients, recur focus be eliminated. Two patients were given sinus debridement surgery alone. All patients were given anti-tuberculosis chemotherapy. The paraplegia was recovered completely in 26 patients, and partly in 5 patients., Conclusions: Inadequate treatment results in defeated operative. The proper selection of operative modalities and timing on the basis of systematically anti-tuberculosis chemotherapy remains the best mode of therapy for spinal tuberculosis complicated with paraplegia. And it is also essential to choose a radical debridement surgery to decompress the spinal cord and to reconstruct the stability of spine.