Two-Year Duration of Immunity of Inactivated Poliovirus Vaccine: A Follow-up Study in Pakistan in 2020.

This was a follow-up study conducted in 2020 assessing changes in levels of type 2 poliovirus-neutralizing antibodies 2 years postimmunization in children who received inactivated poliovirus vaccine (IPV) in Karachi, Pakistan. Unexpectedly, the findings revealed an increase in seroprevalence of type 2 antibodies from 73.1% to 81.6% 1 year and 2 years after IPV, respectively. The increase in type 2 immunity could result from the intensive transmission of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Karachi during the second year of IPV administration. This study suggests that the cVDPV2 outbreak detected in Pakistan infected large proportions of children in Karachi. Clinical Trials Registration . NCT03286803.

Cell-permeable JNK-inhibitory peptide regulates intestinal barrier function and inflammation to ameliorate necrotizing enterocolitis.

Intestinal dysbiosis is believed to play a role in the development of necrotizing enterocolitis (NEC). The efficacy of JNK-inhibitory peptide (CPJIP) in treating NEC was assessed. Treatment with CPJIP led to a notable reduction in p-JNK expression in IEC-6 cells and NEC mice. Following LPS stimulation, the expression of RNA and protein of claudin-1, claudin-3, claudin-4 and occludin was significantly decreased, with this decrease being reversed by CPJIP administration, except for claudin-3, which remained consistent in NEC mice. Moreover, the expression levels of the inflammatory factors TNF-α, IL-1ß and IL-6 were markedly elevated, a phenomenon that was effectively mitigated by the addition of CPJIP in both IEC-6 cells and NEC mice. CPJIP administration resulted in improved survival rates, ameliorated microscopic intestinal mucosal injury, and increased the total length of the intestines and colon in NEC mice. Additionally, CPJIP treatment led to a reduction in serum concentrations of FD-4, D-lactate and DAO. Furthermore, our results revealed that CPJIP effectively inhibited intestinal cell apoptosis and promoted cell proliferation in the intestine. This study represents the first documentation of CPJIP's ability to enhance the expression of tight junction components, suppress inflammatory responses, and rescue intestinal cell fate by inhibiting JNK activation, ultimately mitigating intestinal severity. These findings suggest that CPJIP has the potential to serve as a promising candidate for the treatment of NEC.

Strain evolution from the ferroelectric to the relaxor state in (0.67 - x)BiFeO3-0.33BaTiO3-xBi(Mg0.5Zr0.5)O3 lead-free ceramics.

The BiFeO3-BaTiO3 solid solution exhibits enhanced electric properties due to its modified phase structure with relaxor characteristics and reduced leakage current. Despite these advancements, the underlying mechanism behind the phase transition from a ferroelectric to a relaxor state in BF-BT ceramics remains largely unexplored. Here, the evolution of strain in (0.67 - x)BiFeO3-0.33BaTiO3-xBi(Mg0.5Zr0.5)O3 ceramics is investigated, with a focus on the strain transition from a ferroelectric to a relaxor phase. A strengthening of relaxor behavior is observed in the modified rhombohedral (R) and pseudocubic (PC) phase structure, resulting in optimal strain (Suni = 0.25%, Spos = 0.24%) at x = 0.04. The enhanced strain is attributed to the promotion of domain switching and the presence of strong random fields, with polar nanoregions integrating into a long-range ordered matrix. Furthermore, a gradual increase in strain with rising temperature is noted, driven by increased polarization and the expansion of ferroelectric domains. This study underscores the critical role of structural modifications in augmenting the electric response of BF-BT ceramics, thereby advancing the development of lead-free piezoelectric materials.

Astaxanthin Inhibits H2O2-Induced Excessive Mitophagy and Apoptosis in SH-SY5Y Cells by Regulation of Akt/mTOR Activation.

Oxidative stress, which damages cellular components and causes mitochondrial dysfunction, occurs in a variety of human diseases, including neurological disorders. The clearance of damaged mitochondria via mitophagy maintains the normal function of mitochondria and facilitates cell survival. Astaxanthin is an antioxidant known to have neuroprotective effects, but the underlying mechanisms remain unclear. This study demonstrated that astaxanthin inhibited H2O2-induced apoptosis in SH-SY5Y cells by ameliorating mitochondrial damage and enhancing cell survival. H2O2 treatment significantly reduced the levels of activated Akt and mTOR and induced mitophagy, while pretreatment with astaxanthin prevented H2O2-induced inhibition of Akt and mTOR and attenuated H2O2-induced mitophagy. Moreover, the inhibition of Akt attenuated the protective effect of astaxanthin against H2O2-induced cytotoxicity. Taken together, astaxanthin might inhibit H2O2-induced apoptosis by protecting mitochondrial function and reducing mitophagy. The results also indicate that the Akt/mTOR signaling pathway was critical for the protection of astaxanthin against H2O2-induced cytotoxicity. The results from the present study suggest that astaxanthin can reduce neuronal oxidative injury and may have the potential to be used for preventing neurotoxicity associated with neurodegenerative diseases.

Small Molecule SHP2 Inhibitor LXQ-217 Affects Lung Cancer Cell Proliferation in Vitro and in Vivo.

BACKGROUND: SHP2 is highly expressed in a variety of cancer and has emerged as a potential target for cancer therapeutic agents. The identification of uncharged pTyr mimics is an important direction for the development of SHP2 orthosteric inhibitors. METHODS: Surface plasmon resonance analysis and cellular thermal shift assay were employed to verify the direct binding of LXQ-217 to SHP2. The inhibitory effect of LXQ-217 was characterized by linear Weaver-Burke enzyme kinetic analysis and BIOVIA Discovery Studio. The inhibition of tumor cell proliferation by LXQ-217 was characterized by cell viability assay, colony formation assays and hoechst 33258 staining. The inhibition of lung cancer proliferation in vivo was studied in nude mice after oral administration of LXQ-217. RESULTS: An electroneutral bromophenol derivative, LXQ-217, was identified as a competitive SHP2 inhibitor. LXQ-217 induced apoptosis and inhibited growth of human pulmonary epithelial cells by affecting the RAS-ERK and PI3 K-AKT signaling pathways. Long-term oral administration of LXQ-217 significantly inhibited the proliferation ability of lung cancer cells in nude mice. Moreover, mice administered LXQ-217 orally at high doses exhibited no mortality or significant changes in vital signs. CONCLUSIONS: Our findings on the uncharged orthosteric inhibitor provide a foundation for further development of a safe and effective anti-lung cancer drug.

An Improved YOLOv8 Network for Detecting Electric Pylons Based on Optical Satellite Image.

Electric pylons are crucial components of power infrastructure, requiring accurate detection and identification for effective monitoring of transmission lines. This paper proposes an innovative model, the EP-YOLOv8 network, which incorporates new modules: the DSLSK-SPPF and EMS-Head. The DSLSK-SPPF module is designed to capture the surrounding features of electric pylons more effectively, enhancing the model's adaptability to the complex shapes of these structures. The EMS-Head module enhances the model's ability to capture fine details of electric pylons while maintaining a lightweight design. The EP-YOLOv8 network optimizes traditional YOLOv8n parameters, demonstrating a significant improvement in electric pylon detection accuracy with an average mAP@0.5 value of 95.5%. The effective detection of electric pylons by the EP-YOLOv8 demonstrates its ability to overcome the inefficiencies inherent in existing optical satellite image-based models, particularly those related to the unique characteristics of electric pylons. This improvement will significantly aid in monitoring the operational status and layout of power infrastructure, providing crucial insights for infrastructure management and maintenance.

Robust Fluorometric Aptamer Assay for Direct and Rapid Detection of Clinical Isolates of Candida spec.

Infections caused by yeasts of the genus Candida are likely to occur not only in immunocompromised patients but also in healthy individuals, leading to infections of the gastrointestinal tract, urinary tract, and respiratory tract. Due to the rapid increase in the frequency of reported Candidiasis cases in recent years, diagnostic research has become the subject of many studies, and therefore, we developed a polyclonal aptamer library-based fluorometric assay with high specificity and affinity towards Candida spec. to quantify the pathogens in clinical samples with high sensitivity. We recently obtained the specific aptamer library R10, which explicitly recognized Candida and evolved it by mimicking an early skin infection model caused by Candida using the FluCell-SELEX system. In the follow-up study presented here, we demonstrate that the aptamer library R10-based bioassay specifically recognizes invasive clinical Candida isolates, including not only C. albicans but also strains like C. tropcialis, C. krusei, or C. glabrata. The next-generation fluorometric bioassay presented here can reliably and easily detect an early Candida infection and could be used for further clinical research or could even be developed into a full in vitro diagnostic tool.

A comprehensive overview on the transmission, pathogenesis, diagnosis, treatment, and prevention of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a single positive-strand RNA virus that is responsible for the current pandemic that the world has been facing since 2019. The primary route of transmission of SARS-CoV-2 is through respiratory tract transmission. However, other transmission routes such as fecal-oral, vertical transmission, and aerosol-eye also exist. In addition, it has been found that the pathogenesis of this virus involves the binding of the virus's S protein to its host cell surface receptor angiotensin-converting enzyme 2, which results in the subsequent membrane fusion that is required for SARS-CoV-2 to replicate and complete its entire life. The clinical symptoms of patients infected with SARS-CoV-2 can range from asymptomatic to severe. The most common symptoms seen include fever, dry cough, and fatigue. Once these symptoms are observed, a nucleic acid test is done using reverse transcription-polymerase chain reaction. This currently serves as the main confirmatory tool for COVID-19. Despite the fact that no cure has been found for SARS-CoV-2, prevention methods such as vaccines, specific facial mask, and social distancing have proven to be quite effective. It is imperative to have a complete understanding of the transmission and pathogenesis of this virus. To effectively develop new drugs as well as diagnostic tools, more knowledge about this virus would be needed.

Preparation of the endometrium for frozen embryo transfer: an update on clinical practices.

Over the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle are two popular methods for preparing the endometrium. Hormone replacement therapy is now used at the discretion of the doctors because it is easy to coordinate the timing of embryo thawing and transfer with the schedules of the in-vitro fertilization lab, the treating doctors, and the patient. However, current results suggest that establishing a pregnancy in the absence of a corpus luteum as a result of anovulation may pose significant maternal and fetal risks. Therefore, a 'back to nature' approach that advocates an expanded use of natural cycle FET in ovulatory women has been suggested. Currently, there is increasing interest in how the method of endometrial preparation may influence frozen embryo transfer outcomes specifically, especially when it comes to details such as different types of ovulation monitoring and different luteal support in natural cycles, and the ideal exogenous hormone administration route as well as the endocrine monitoring in hormone replacement cycles. In addition to improving implantation rates and ensuring the safety of the fetus, addressing these points will allow for individualized endometrial preparation, also as few cycles as possible would be canceled.

Skeletal muscle HSF1 prevents insulin resistance by improving glucose utilization.

The regulation of muscle glucose utilization has significant potential for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Heat shock factor 1 (HSF1) is involved in cellular metabolism and regulation of muscle metabolism. However, it is unclear how HSF1 regulates muscle glucose metabolism. In the present study, the development of obesity in mice was associated with HSF1 downregulation. Serum samples and muscle biopsies were obtained from obese and healthy humans. Fasting glucose and insulin levels and the homeostasis model assessment of insulin resistance value showed that obesity was associated with insulin resistance. The skeletal muscle level of HSF1 was decreased in obese and ob/ob mice. HSF1 was selectively over-expressed in the skeletal muscles of high fat diet (HFD)-fed mice. Muscle HSF1 over-expression successfully triggered glycolytic-to-oxidative myofiber switch and increased fatty acid metabolism and insulin sensitivity in the skeletal muscles of HFD-fed mice. Moreover, HSF1 improved energy expenditure and blocked muscle accumulation of triglycerides in HFD-fed mice. Consequently, muscle HSF1 mitigated the impaired muscle insulin signaling and insulin resistance in HFD-fed mice. In conclusion, T2DM and obesity in HFD-fed mice may be treated with selective HSF1-directed programming of exercise-like effects in skeletal muscle. These findings may aid the development of a new therapeutic approach for obesity and T2DM.

An interval water demand prediction method to reduce uncertainty: A case study of Sichuan Province, China.

Effective prediction of water demand is a prerequisite for decision makers to achieve reliable management of water supply. Currently, the research on water demand prediction focuses on point prediction method. In this study, we constructed a GA-BP-KDE hybrid interval water demand prediction model by combining non-parametric estimation and point prediction. Multiple metaheuristic algorithms were used to optimize the Back-Propagation Neural Network (BP) and Kernel Extreme Learning Machine (KELM) network structures. The performance of the water demand point prediction models was compared by the Root Mean Squared Error (RMSE), Mean Absolute Percentage Error (MAPE), Kling-Gupta Efficiency (KGE), computation time, and fitness convergence curves. The kernel density estimation method (KDE) and the normal distribution method were used to fit the distribution of errors. The probability density function with the best fitting degree was selected based on the index G. The shortest confidence interval under 95% confidence was calculated according to the asymmetry of the error distribution. We predicted the impact indicator values for 2025 using the exponential smoothing method, and obtained water demand prediction intervals for various water use sectors. The results showed that the GA-BP model was the optimal model as it exhibited the highest computational efficiency, algorithmic stability, and prediction accuracy. The three prediction intervals estimated after adjusting the KDE bandwidth parameter covered most of the sample points in the test set. The prediction intervals of the four water use sectors were evaluated as F values of 1.6845, 1.3294, 1.6237, and 1.3600, which indicates high accuracy and quality of the prediction intervals. The mixed water demand interval prediction based on GA-BP-KDE reduces the uncertainty of the point prediction results and can provide a basis for water resource management by decision makers.

The potential mechanism of Choulingdan mixture in improving acute lung injury based on HPLC-Q-TOF-MS, network pharmacology and in vivo experiments.

Choulingdan mixture (CLDM) is an empirical clinical prescription for the adjuvant treatment of acute lung injury (ALI). CLDM has been used for almost 30 years in the clinic. However, its mechanism for improving ALI still needs to be investigated. In this study, high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) was applied to characterize the overall chemical composition of CLDM. A total of 93 ingredients were characterized, including 25 flavonoids, 20 organic acids, 11 saponins, nine terpenoids, seven tannins and 21 other compounds. Then network pharmacology was applied to predict the potential bioactive components, target genes and signaling pathways of CLDM in improving ALI. Additionally, molecular docking was performed to demonstrate the interaction between the active ingredients and the disease targets. Finally, animal experiments further confirmed that CLDM significantly inhibits pulmonary inflammation, pulmonary edema and oxidative stress in lipopolysaccharide-induced ALI mice by inhibiting the PI3K-AKT signaling pathway. This study enhanced the amount and accuracy of compounds of CLDM and provided new insights into CLDM preventing and treating ALI.

Letrozole use in vitrified single-blastocyst transfer cycles is associated with lower risk of large for gestational age infants in patients with polycystic ovary syndrome.

PURPOSE: To evaluate the obstetric and perinatal outcomes of three routine endometrial preparation protocols in women with PCOS who underwent frozen embryo transfer (FET). METHODS: This was a retrospective study in women with PCOS who underwent FET in an academic reproductive medical center. A total of 2710 cycles were enrolled and classified into three groups according to different endometrial preparation protocols; human menopausal gonadotropin (HMG), letrozole + HMG, or hormone replacement therapy (HRT). RESULTS: The stimulation groups had reduced risks of hypertensive disorders of pregnancy (HDP), large for gestational age (LGA) infants, and cesarean delivery than the HRT group. After adjustment for different confounder combinations in the two models, the frequencies of LGA and HDP in the letrozole + HMG group and the HMG group were still significantly lower than those in the HRT group. The letrozole + HMG group exhibited a reduced risk of LGA than HMG group after adjustment of confounders. A trend toward risk reductions in HDP and LGA was observe in turns of HRT, HMG, and letrozole + HMG groups, and the trends were statistically significant (Ptrend = 0.031 and 0.001). CONCLUSION: In patients with PCOS, ovarian stimulation protocols for endometrial preparation are associated with reduced risks of HDP and LGA compared to HRT cycles. The use of letrozole could further reduce risk of LGA compared to HMG only protocol. We propose that ovarian stimulation protocols can be used widely for endometrial preparation in FET cycles in women with PCOS, especially with the use of letrozole.

Using Digestion by IdeS Protease to Improve Quantification of Degradants in Monoclonal Antibodies by Non-Reducing Capillary Gel Electrophoresis.

Monoclonal antibodies (mAbs) have become predominant therapeutics by providing highly specific mechanisms of action enabling treatment of complex diseases. However, mAbs themselves are highly complex and require thorough testing and characterization to ensure efficacy and patient safety. In this regard, fragmentation is a degradation product of concern. The biotechnology industry uses capillary gel electrophoresis (CGE) to quantify fragmentation by electrophoretically resolving size variants, such as products resulting from partial reduction of interchain disulfides. However, standard CGE methods may not adequately separate less typical fragments, particularly when there is minimal size difference to the parent molecule. For mAb-1, a degradant only ∼11 kDa smaller than the intact mAb (∼149 kDa) was unable to be resolved under typical non-reducing conditions, preventing an accurate purity assessment and precluding tracking of product purity within stability studies. To address these deficiencies, a subunit-based non-reducing CGE method was developed to employ IdeS protease to produce F(ab')2 and Fc fragments, which resulted in baseline resolution of the clipped subunit species from its parent species. This enabled more accurate trending of purity throughout stability studies. Method characterization ensured that this subunit method monitored expected impurities observed by intact non-reducing CGE and thus could suitably replace non-reducing CGE in the release and stability testing panel. It also has the potential to replace reducing CGE based on its tracking of the deglycosylated Fc species. We believe this approach of utilizing proteases to develop subunit CGE methods for release and stability can be applied to other molecules when in need of resolving analogous fragments.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus and risk factors in Jiuquan area, China.

The seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) is high in Xinjiang, China. But the seroprevalence of KSHV and risk factors are still unknown in Gansu which is adjacent to Xinjiang. Six hundred and seventy-eight serum samples of the general population and 87 serum samples of syphilis patients from Jiuquan, Gansu were tested for antibodies against KSHV, including one latent protein (ORF73) and two lytic proteins (ORF65 and K8.1) using the ELISA. The total KSHV-seropositive rate was 15.9% in 678 serum samples in the Jiuquan area, and the KSHV-seropositive rate of males was higher than females (18.0% vs. 14.6%, p > 0.05). The Uygur, Kazakh, Hui, Manchu, and Mongolian populations had a higher seroprevalence of KSHV than the Han population (43.8%, 40.0%, 34.5%, 30.3%, 35.0% vs. 11.0%, respectively) among the ethnic groups in Jiuquan. Compared to the Han, Uygur, Kazak, Hui, Manchu, and Mongolian people had an increase in the risk of KSHV of 528.9%, 439.1%, 325.6%, 251.6%, and 335.4% (p < 0.001, p < 0.001, p < 0.001, p = 0.002, p = 0.003, respectively). The serum prevalence of KSHV in subjects aged < 20 years, 20-50 years, and >50 years was 13.8%, 14.7%, and 20.1%, respectively. Compared to the subjects aged < 20 years, 20-50 years and >50 years had an increase in the risk of KSHV of 7.4% and 56.9% (p = 0.829 and p = 0.204, respectively). Compared to the positive rate of KSHV in the general population of Anhui, the positive rate of KSHV was significantly higher in the general population of the Jiuquan area (15.9% vs. 9%, p < 0.01). There was no significant difference in the positive rate of KSHV between the Han population of Jiuquan and the Han population of Anhui (p > 0.05). In the population of syphilis patients in the Jiuquan area, the positive rate of KSHV was 30.7%, which was higher than that of the general population in the Gansu area (p < 0.05). This study indicates that Gansu has a high seroprevalence of KSHV. Ethnicity and syphilis are risk factors for KSHV infection.

Endometrial thickness is an independent risk factor of hypertensive disorders of pregnancy: a retrospective study of 13,458 patients in frozen-thawed embryo transfers.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are an important cause of maternal and fetal mortality, and its potential risk factors are still being explored. Endometrial thickness (EMT), as one of the important monitoring indicators of endometrial receptivity, has been confirmed to be related to the incidence of HDP in fresh embryo transfer. Our study was designed to investigate whether endometrial thickness is associated with the risk of hypertensive disorders of pregnancy in frozen-thawed embryo transfer (FET). METHODS: This respective cohort study enrolled 13,458 women who received vitrified embryo transfer and had a singleton delivery in the Reproductive Hospital affiliated to Shandong University from January 2015 to December 2019. We set strict screening criteria and obtained the information from the hospital electronic medical system. Statistical methods including logistic regression analysis, receiver operating characteristic curve and restricted cubic spline were used to evaluate the relationship between endometrial thickness and the incidence of pregnancy-induced hypertension. RESULTS: The incidences of HDP in a thin endometrial thickness group (< 0.8 cm) and a thick endometrial thickness group (> 1.2 cm) were significantly greater than in a reference group (0.8 cm-1.2 cm) (7.98 and 5.24% vs 4.59%, P <  0.001). A nonlinear relationship between endometrial thickness and risk of hypertensive disorders of pregnancy was examined by restricted cubic spline (P <  0.001). The thin endometrial thickness and thick endometrial thickness groups were significantly associated with the risk of HDP after adjusting for confounding variables by stepwise logistic regression analysis. Subsequently, subgroup logistic regression analysis based on endometrial preparation regimens showed that thin endometria were still significantly associated with a higher morbidity rate in the artificial cycle group, while in the natural cycle group, thick endometria were closely associated with increased morbidity. CONCLUSION: Our study manifested that both the thin and thick endometria were associated with an increased risk of hypertensive disorders of pregnancy in frozen embryo transfer cycles. Reproductive clinicians should focus on adjusting endometrial thickness in different preparation regimens; and obstetricians should be mindful of the risk of hypertension during pregnancy, when women with thin (< 0.8 cm) or excessively thicker (> 1.2 cm) endometrial thickness achieve pregnancy through frozen-thawed embryo transfer.

The Gut-Liver Axis in Nonalcoholic Fatty Liver Disease: Association of Intestinal Permeability with Disease Severity and Treatment Outcomes.

Objective: To investigate the association between intestinal permeability and severity of nonalcoholic fatty liver disease (NAFLD) and the value of intestinal permeability in predicting the efficacy of metabolic therapy for NAFLD. Methods: Disease severity was compared between patients with normal and elevated intestinal permeability; correlations between D-lactate and different NAFLD parameters were analyzed; and the effects of metabolic therapy on NAFLD patients with normal and elevated intestinal permeability were evaluated. Results: A total of 190 patients with NAFLD were enrolled. NAFLD patients with elevated intestinal permeability had significantly higher levels of liver test parameters, liver ultrasonographic fat attenuation parameter, triglyceride, homeostasis model assessment of insulin resistance value, and diamine oxidase (all P˂0.05) than NAFLD patients with normal intestinal permeability. Furthermore, serum D-lactate levels were positively correlated with alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, total bilirubin, indirect bilirubin, fat attenuation parameter, triglyceride, and diamine oxidase (all P ˂ 0.05). Moreover, NAFLD patients with elevated intestinal permeability showed less improvement in TG levels (P = 0.014) after metabolic therapy. Conclusion: Intestinal permeability correlates with the disease severity in patients with NAFLD. Moreover, intestinal permeability may have value for predicting the efficacy of metabolic therapy for NAFLD patients.

Natural cycles achieve better pregnancy outcomes than artificial cycles in non-PCOS women undergoing vitrified single-blastocyst transfer: a retrospective cohort study of 6840 cycles.

PURPOSE: To identify the optimal method for endometrial preparation in vitrified single-blastocyst transfer (VSBT) cycles. METHODS: This was a retrospective cohort study for non-PCOS patients who underwent VSBT cycles from March 2015 to November 2019 in an academic reproductive medical center. A total of 6840 VSBT cycles were enrolled and classified into two groups according to different endometrial preparation methods. RESULTS: The non-PCOS patients who underwent VSBT showed a significantly higher clinical pregnancy rate (61.96% vs 56.85%, p < 0.001) and live birth rate (49.09% vs 39.86%, p < 0.001), as well as a statistically lower early miscarriage rate (12.02% vs 18.08%, p < 0.001) in the natural cycle (NC) group compared with the artificial cycle (AC) group. Multivariable analysis further confirmed that NC was associated with an increased likelihood of clinical pregnancy (adjusted odds ratio (aOR) 0.852, 95% confidence interval (CI) 0.765-0.949, p = 0.004) and live birth (aOR 0.746, 95% CI 0.669-0.832, p < 0 .001), but decreased early miscarriage occurrence (aOR 1.447, 95% CI 1.215-1.724, p < 0.001) compared to AC. CONCLUSIONS: Our study demonstrated that non-PCOS patients could benefit from NC in vitrified blastocyst transfer. Increased clinical pregnancy rate and decreased early miscarriage rate led to a significantly higher live birth rate in NC patients compared with AC with our present protocol.

Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene, which is involved in the RAS/MAPK cell signaling transduction process. SHP2 has been shown to contribute to the progression of various cancers and is emerging as an important target for anti-tumor drug research. However, past efforts to develop SHP2 inhibitors into drugs have been unsuccessful owing to the positively charged nature of the active site pocket tending to bind negatively charged groups that are usually non-drug-like. Here, a series of uncharged pyrazoline derivatives were designed and developed as new SHP2 inhibitors using a structure-based strategy. Compound 4o, which exhibited the strongest SHP2 inhibitory activity, bound directly to the catalytic domain of SHP2 in a competitive manner through multiple hydrogen bonds. Compound 4o affected the RAS/MAPK signaling pathway by inhibiting SHP2, and subsequently induced apoptosis and growth inhibition of HCT116 cells in vitro and in vivo. Notably, the oral administration of compound 4o in large doses showed no obvious toxicity. In summary, our findings provide a basis for the further development of compound 4o as a safe, effective and anti-tumor SHP2 inhibitor.

A Polyclonal Aptamer Library for the Specific Binding of the Gut Bacterium Roseburia intestinalis in Mixtures with Other Gut Microbiome Bacteria and Human Stool Samples.

Roseburia intestinalis has received attention as a potential probiotic bacterium. Recent studies have demonstrated that changes in its intestinal abundance can cause various diseases, such as obesity, enteritis and atherosclerosis. Probiotic administration or fecal transplantation alter the structure of the intestinal flora, offering possibilities for the prevention and treatment of these diseases. However, current monitoring methods, such as 16S rRNA sequencing, are complex and costly and require specialized personnel to perform the tests, making it difficult to continuously monitor patients during treatment. Hence, the rapid and cost-effective quantification of intestinal bacteria has become an urgent problem to be solved. Aptamers are of emerging interest because their stability, low immunogenicity and ease of modification are attractive properties for a variety of applications. We report a FluCell-SELEX polyclonal aptamer library specific for R. intestinalis isolated after seven evolution rounds, that can bind and label this organism for fluorescence microscopy and binding assays. Moreover, R. intestinalis can be distinguished from other major intestinal bacteria in complex defined mixtures and in human stool samples. We believe that this preliminary evidence opens new avenues towards aptamer-based electronic biosensors as new powerful and inexpensive diagnostic tools for the relative quantitative monitoring of R. intestinalis in gut microbiomes.