The expression of UNC5D is abnormal in the early stage of colorectal tumors associated with its proliferation and migration.

OBJECTIVE: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. MATERIALS AND METHODS: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. RESULTS: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. CONCLUSIONS: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression.

[Research and discovery of "inner GPS" of brain].

Since the 20th century, with the progress of brain science research, scientists have discovered the brain GPS, revealing the mechanism of brain spatial cognition. The discovery process of brain GPS has gone through three stages. In 1971, John O'Keefe discovered the position cells in the hippocampus of the brain, which was the beginning of the research on the GPS in the brain; In 1900, James Rank discovered the head direction cells in the medial entorhinal cortex of the brain, and the research on the GPS in the brain made a breakthrough; In 2005, Edvard I. Moser and his wife discovered grid cells, marking the maturity of the research on GPS in the brain. The discovery of intracerebral GPS not only reveals the spatial cognitive function of the brain at the cellular level, but also provides a theoretical basis for the study of diseases related to the nervous system.

[Comparative study of next generation sequencing and immunohistochemistry on molecular classification of endometrial carcinoma].

Objective: To investigate the differences in molecular classification of endometrial carcinoma (EC) between various technical methods and to explore molecular classification schemes suitable for Chinese population. Methods: The study used a comprehensive scheme of next generation sequencing (NGS) and immunohistochemistry for molecular classification of 254 EC cases that were obtained at Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from April 2021 to March 2022. According to the recommended threshold of Sanger sequencing which was approximate-20% variant allele fraction (VAF), NGS data were extracted to simulate the results of Sanger sequencing. Results: The 254 EC patients had a mean age of 51 years (range, 24 to 89 years). Combination of POLE (9-14 exons), TP53 total exons and microsatellite instability (MSI) detection was a better single scheme than NGS alone, while combination of MSI fragment analysis and conventional immunohistochemistry was the best solution and seemed best aligned with TCGA data and recent studies. POLE ultramuted type, mismatch repair defect type, TP53 mutant type and non-specific molecular characteristic type accounted for 11.4% (29/254), 31.5% (80/254), 22.4% (57/254) and 34.6% (88/254) of the cases, respectively. If Sanger sequencing was adopted for POLE and TP53 detection, the frequencies of these EC types were 9.1% (23/254), 31.5% (80/254), 12.9% (33/254) and 46.6% (118/254), respectively, with greatly increasing non-specific molecular characteristics cases. If POLE was detected by Sanger sequencing and others by immunohistochemistry, they were 9.1% (23/254), 42.2% (92/218), 13.8% (35/254) and 40.9% (105/254), respectively, with increasing the false positive rates of the mismatch repair defect group. Conclusions: Small and medium-sized NGS panels with MSI detection is a better solution than NGS alone. Sanger sequencing is currently available for POLE mutation detection, which is not sensitive enough for TP53 mutation detection, and seems equivalent to the efficiency of TP53 by immunohistochemistry. Further optimization of small and medium-sized NGS panels covering MSI detection and POLE and TP53 full exons may be the best choice for the future to meet national conditions.

[Investigation and analysis on the detection of IgG antibodies against the rubella virus among rural childbearing-age women in preconception period in Yunnan Province from 2013 to 2019].

A study was conducted on rural women of childbearing age aged 20-49 who underwent the National Free Preconception Health Examination Project (NFPHEP)in Yunnan Province from 2013 to 2019. Descriptive analysis was conducted to determine the negative rate of IgG antibodies against the rubella virus and its differences among various socio-demographic characteristics. Among the 1 511 203 study subjects, the negative rate of IgG antibodies against the rubella virus was 24.36%. Only 2.64% of the population had received rubella virus vaccine. The negative rate of IgG antibodies among rural childbearing-age women in the preconception period in Yunnan Province decreased with age and educational level (Ptrend<0.001). The negative rate of IgG antibodies in ethnic minority women of childbearing age in the preconception period (25.19%) was higher than that of Han women (23.88%). Among the 22 ethnic groups with over 1 000 participants, the negative rates of IgG antibodies in women of childbearing age from the Blang (32.85%), Bouyei (31.03%), Zhuang (31.01%), and Miao (30.70%) ethnic groups were higher than those of women from other ethnic groups. Among the 16 states (cities) in Yunnan Province, the negative rate of IgG antibodies in pregnant women of childbearing age in Wenshan Zhuang and Miao Autonomous Prefecture (38.06%) and Lincang City (32.63%) was higher than that in other states (cities). The negative rate of serum IgG antibodies in women who reported having received rubella virus vaccine (18.60%) was lower than that in other non-vaccinated populations (24.52%). The proportion of rural women of childbearing age in Yunnan Province who were susceptible to the rubella virus before pregnancy was still high. It is necessary to promote rubella vaccination among people susceptible to rubella, especially pregnant women, to prevent rubella virus infection and reduce the incidence rate and disease burden of rubella people.

[Clinical follow-up analysis of multidisciplinary treatment of children with spinal muscular atrophy].

Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t-test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 (P=0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t=-4.13, P<0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t=-0.24, 1.36, 1.21; all P>0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z=-3.01, P=0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z=2.44, 3.11, P=0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.

[Value of high-risk HPV E6/E7 mRNA in situ hybridization in grading of cervical intraepithelial neoplasia].

Objective: To investigate the value of high-risk HPV E6/E7 mRNA in situ hybridization in the grading of cervical squamous intraepithelial neoplasia (CIN). Methods: A total of 261 cases with diagnosis of CIN and cervical squamous cell carcinoma (SCC) at west China University Second Hospital, Sichuan University from July 2019 to June 2020 were collected, including 60 cases of CIN1, 41 cases of CIN2, 51 cases of CIN3, 72 cases of SCC, and 37 cases of normal cervical control tissue (10 HPV negative and 27 HPV positive). All pathologic tissues were made into tissue microarrays, and HE staining, HPV E6/E7 mRNA in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining were performed respectively. The staining was assessed by light microscopy, and the positive rate and positive pattern were analyzed statistically. Results: HPV mRNA ISH in CIN1 mainly showed spot staining in predominantly basal to mid-epithelial layers (≤BME) with a diffuse nuclear signals in the superficial layer (supD), that is, the pattern of ≤BME+supD; in CIN2, it mainly showed spot staining in predominantly basal to above mid-epithelial but not the full layer (>BME) and some cases with supD staining, that is, the pattern of>BME+supD; In CIN3, the mainly pattern was >BME, and the spot staining was distributed throughout the epithelium. In CIN1, CIN2 and CIN3, there were significantly statistical differences among the above three staining patterns (P<0.05). Conclusions: HPV mRNA ISH contributes to the accurate diagnosis and grading of CIN, and has better specificity than p16 IHC staining.

Abnormal keratin expression pattern in prurigo nodularis epidermis.

Background: Prurigo nodularis (PN) is a highly pruritic, chronic dermatosis and difficult to treat. PN lesions are characterized by existence of many hyperkeratotic, erosive papules and nodules. However, the pathogenesis of PN still remains unelucidated. Aim: To clarify the keratin role in the epidermis hyperproliferation, the keratin expression pattern in the PN lesional skin. Methods: In this study, we enrolled 24 patients with PN and 9 healthy control volunteers. K1/K10, K5/K14, K6/K16/K17 expression pattern were investigated by using immunohistochemical staining. Results: The lesional skin consists of the thickened spinous layers, in which active cell division was found. K5/K14 were upregulated in PN lesional epidermis, the staining signal localized in the basal layer and lower suprabasal layers. Hyperproliferation-associated K6 was found in all layers of epidermal lesional skin, especially in the spinous layers. In contrast, K16 was only detected in the basal and lower suprabasal layers, K17 was observed in the basal and spinous layers. Terminal differential keratins K1/K10 were upregulated, detected in the pan-epidermis, but spared in the basal and low suprabasal layers. Conclusion: The keratinocytes enter an alternative differentiation pathway, which are responsible for the activated keratinocyte phenotype, abnormal keratins expression potentially contributes to the keratinocytes proliferation, subsequently lead to increased lesional skin epidermis thickness, hyperkeratiosis and alteration of skin barrier properties.

[Clinical follow-up analysis of nusinersen in the disease-modifying treatment of pediatric spinal muscular atrophy].

Objective: To explore the clinical efficacy of disease-modifying drug nusinersen on children with spinal muscular atrophy. Methods: The baseline and longitudinal clinical data of 15 children who were treated with nusinersen in the Children's Hospital, Zhejiang University School of Medicine from October 2019 to October 2021 were retrospectively collected. The general data (gender, age, genotype, and clinical classification, etc.), motor function, nutritional status, scoliosis and respiratory function were analyzed. Wilcoxon rank-sum test was used for comparing multi-system conditions before and after treatment. Results: The age of 15 cases (7 males, 8 females) was 6.8 (2.8, 8.3) years, with 2 cases of type 1, 6 cases of type 2, and 7 cases of type 3 respectively, and the course of disease was 55.0 (21.0, 69.0) months. After 9.0 (9.0, 24.0) months of treatment, the motor function scale evaluations of the Hammersmith neurological examination section 2 (13.0 (7.0, 23.0) vs. 18.0 (10.0, 25.0) scores, Z=-2.67, P=0.018) of 15 children, the Hammersmith functional motor scale expanded (38.0 (18.5, 45.5) vs. 42.0 (23.0, 51.0) scores, Z=-2.38, P=0.018), and the revised upper limb module (27.0 (19.5, 32.0) vs. 33.0 (22.5, 35.5) scores, Z=-2.52, P=0.012) of children with type 2 and 3 had significantly improved. Thirteen patients achieved clinically significant motor function improvement, and 2 of them had kept stable scale scores. Subjective reports also indicated that the muscle strength and daily exercise ability of these children improved after treatment, and no serious adverse reactions were reported. Supplemented by the multi-disciplinary team management, the levels of some indicators such as Cobbs angle of scoliosis and forced vital capacity all had significantly improved (all P<0.05). Conclusions: Nusinersen can improve the motor function of patients with 5q spinal muscular atrophy, which is also proved safe to be used in children. The drug treatment supplemented by the multi-disciplinary team management is helpful to improve the multi-system function of the children with spinal muscular atrophy.

[Idiopathic pleuroparenehymal fibroelastosis: five case reports and review of literature].

Objective: To raise the awareness of idiopathic pleuroparenehymal fibroelastosis (iPPFE) through investigating the clinical, radiographic and pathological features. Methods: Five cases of iPPFE proved by pathology. The clinical data were studied respectively, and the relevant literature was reviewed. Results: All the cases of iPPFE were manifested by cough and dyspnea. The patients including 3 males and 2 females, aged from 30 to 70 years Chest CT scan showed pleural thickening, subpleural consolidation in both upper lungs complicated with tractive bronchiectasis.Computed tomography-guided percutaneous lung biopsy or surgical lung were performed and the same pathological showed pleura and subpleural dense elastic and collagen fibers. The elastic fibers stain was also positive,which was consistent with PPFE. One patient received low-dose corticosteroid, two received pirfenidone therapy, the others received no treatment. Three patients were stable during the follow-up. Conclusions: iPPFE has characteristic pathological features. However, the number of clinically reported cases is low due to missed diagnosis or misdiagnosed. Improving the understanding of features of iPPFE is helpful for the dianosis, therapy, and prognosis of this disease.

[Impact of probiotics on the lung development of Bama minipig after premature birth].

Objectives: To examine the impact of probiotics on the lung development of preterm birth of Bama pig. Methods: From April 2020 to October 2021, this animal experimental research was performed by setting up preterm (birth at gestation 104 d), full-term (birth at gestation 113 d), preterm with probiotics (birth at gestation 104 d treated with probiotics given at 3 d after birth), and full-term with probiotics (birth at gestation 113 d treated with probiotics given at 3 d after birth) groups and using the preterm Bama minipig model, the body weights were recorded and lung, ileum, and intestinal content samples were collected at birth, 4 days, 9 days, and 21 days after births of the piglets in preterm and full-term groups, the same samples were collected on 9 days after births of the piglets in preterm with probiotics and full-term with probiotics groups. The body weight and radial alveolar counts (RAC) were compared to evaluate the lung development of the piglets. The lengths of ileal villus were compared to evaluate the development of ileum. The composition structures of bacteria in ileum were analyzed by 16 S rRNA sequencing. The statistical analyses between different groups were performed by t test. Results: There were totally 30 piglets (16 female piglets and 14 male piglets) involving 12 piglets in preterm and full-term groups respectively and 3 piglets in preterm with probiotics and full-term with probiotics groups respectively. The body weights of the piglets in preterm group were lower than those in full-term group at 4, 9 and 21 d after birth ((507±27) vs. (694±56) g, (620±35) vs. (1 092±154) g, (1 660±210) vs. (2 960±418) g,t=2.96, 2.99, 2.78, all P<0.05). The alveolarization of the preterm piglets at 9 days after birth was significantly lower than that of the full-term piglets at the equivalent time point (4.00±0.29 vs. 6.11±0.35, t=4.64, P<0.01). The bacteria genus with the highest abundance in ileum were all different between the preterm and the full-term groups at 4, 9 and 21 d after birth (4 d Escherichia-Shigella (26.63%) and Enterococcus (30.48%) respectively;9 d Turicibacter (35.94%) and Lactobacillus (27.33%) respectively;21 d Escherichia-Shigella (28.02%) and Lactobacillus (46.29%) respectively). The heights of ileal villus of the preterm piglets at 9 d after birth were significantly lower than those of the full-term minipigs at the equivalent time point ((297±21) vs. (411±32) µm, t=3.01, P=0.007).There were both no differences in the body weight and alveolarization ((692±36) vs. (767±67) g, 5.44±0.34 vs. 5.89±0.26, t=0.74, 1.04, both P>0.05) between the piglets in preterm with probiotics group and those in full-term with probiotics group. Turicibacter was the dominant genus in the piglets of both preterm with probiotics and the full-term with probiotics groups. The heights of ileal villus of the piglets in preterm with probiotics group were significantly longer that those of the piglets in preterm group ((371±13) vs. (297±21) µm, t=3.04, P=0.006), and were both not significantly different from those of the piglets in full-term with probiotics group and full-term group ((371±13) vs. (338±12) and (411±32) µm, t=1.90, 1.15, both P>0.05). Conclusions: Premature birth could impact the lung alveolarization of piglets. The probiotics could improve the lung alveolarization of preterm minipigs by promoting the development of ileum.

[Interim follow-up of fetal cardiac intervention in five fetuses with pulmonary atresia with intact ventricular septum].

Objective: To summarize the interim outcome and right heart development of pulmonary atresia with intact ventricular septum (PA-IVS) in children after fetal cardiac intervention (FCI). Methods: The clinical data of 5 live births underwent FCI from October 2018 to April 2019 in Women and Children's Hospital, Qingdao University were analyzed retrospectively. The development of right ventricle (RV) and tricuspid valve (TV) in uterus after FCI, at birth, the age of 6 months, 1 year and 2 years, and the final outcome were assessed. Results: Five PA-IVS fetuses were included in this study. The first evaluation was performed at 24-26 weeks of gestational age, and the FCI was performed at 26-28 weeks of gestational age. During the follow-up of 6 weeks after FCI, the minimum diameter of tricuspid annulus increased from 0.85 cm to 0.92 cm, and the minimum Z-score of tricuspid annulus decreased from -0.03 to -1.62. The minimum values of TV/mitral valve annular diameter and RV/left ventricular length ratios of all fetuses increased from 0.57, 0.52 to 0.88, 0.82, respectively. The maximum tricuspid regurgitation velocity decreased from 4.60 m/s to 3.64 m/s. No severe hemodynamic change was found in any of the fetuses. All 5 fetuses were born alive. Three cases underwent percutaneous balloon pulmonary valvuloplasty (PBPV) and stent implantation for ductus arteriosus. Two cases received PBPV alone. At follow-up (26 to 32 months), obvious development of TV was observed 6 months to 1 year after birth in 5 cases with the growth rate ranging from 19.64% to 40.00%. Meanwhile, the RV development was relatively slow at 6 months with the growth rate ranging from 9.41% to 21.42%. There were individual differences in RV development at 2 years. The growth and development of all children were equal to healthy children of the same age with the body mass index less than 18.4 kg/m2. At the last follow-up, all children had a transcutaneous oxygen saturation of greater than 0.95, three became biventricular circulation and two had circulation approximation to biventricular circulation with almost closed stent. Conclusions: The findings support the potential of development of right ventricular and tricuspid valve for fetuses with PA-IVS underwent FCI. All fetuses underwent FCI received intervention after birth, and biventricular circulation can be realized finally. The development of right ventricular and tricuspid valve is not proportional. In utero, the right ventricle develops rapidly, and the development of tricuspid valve is more advantageous after birth.

Trace analysis of therapeutic inertia and subsequent hemoglobin A1c outcomes in a 2-year cohort study.

OBJECTIVE: Our understanding of therapeutic inertia in diabetes care is incomplete in terms of an assessment across a nationwide population. The key objectives of this investigation were to measure therapeutic inertia and link this phenomenon to the important surrogate outcome of hemoglobin A1c (HbA1c) control in a nationwide cohort. PATIENTS AND METHODS: We performed a retrospective cohort study over 18 months. Laboratory and prescription data were collected for 41,948 patients (women: 53.1%) with diabetes who had at least two HbA1c results. The association between treatment intensity and glycemic control, using the change in HbA1c during the observation period, and whether the HbA1c outcome was greater than 9% were examined. RESULTS: Among the patients who exhibited a secondary HbA1c result exceeding 9%, 8,630 (78.26%) had undergone intensified therapy at the time of the index HbA1c measurement, and among these patients, the incidence ratio of the last HbA1c outcome exceeding 9% after 6 to 18 months was 0.779-fold (95% Cl 0.728 to 0.834) greater than those who had not received intensified therapy (p < .001). CONCLUSIONS: After tracking patient data for a particular period, we found that patients with diabetes who received intensified therapy achieved surrogate outcomes of HbA1c control that were more favorable.

[Fetal cardiac intervention and perioperative management of fetus with hypoplastic right heart syndrome].

Objective: To summarize the experience of perioperative management strategy of fetal pulmonary valvuloplasty (FPV) for hypoplastic right heart syndrome (HRHS). Methods: In the retrospective study of perioperative data, 13 fetuses of HRHS were treated with FPV in Qingdao Women and Children's Hospital from July 2018 to June 2019. Results: (1) The evaluation indexes of the right ventricle in 13 fetuses before FPV: the mean ratio of tricuspid/mitral annulus, right/left ventricular length, pulmonary/aortic annulus, and tricuspid inflow time/cardiac cycle were 0.81±0.04, 0.56±0.14, 0.69±0.06, and 0.35±0.03, respectively. (2) All pregnant mothers underwent general anesthesia. The basic fetal heart rate was (156±12) beats per minutes before FPV, and 9 fetuses showed bradycardia during the operation, and recovered to normal after drug resuscitation. On the first day after FPV, two cases had bradycardia and pregnancy was terminated. The fluctuation of systolic blood pressure of pregnant mother was less than 20%, and there was no significant difference between preoperative and intraoperative pulse pressure [(36.0±5.6) vs (35.8±6.9) mmHg (1 mmHg=0.133 kPa); t=8.102, P=0.951]. (3) All cases of HRHS fetus successfully underwent FPV. The average gestational age was (27.3±0.8) weeks. The average operation time was (23.2±1.0) minutes. The ratio of tricuspid to mitral annulus (t=-2.513, P=0.022) and the ratio of right to left ventricular length (t=-3.373, P=0.003) were significantly improved at 6 weeks postoperatively. Ten fetuses were delivered, and there was no death after early intervention. (4) Of 13 pregnant women, 3 cases were nausea and vomiting on the day of FPV operation, the treatment of the symptoms was improved by tropisetron; one case had tolerable abdominal pain and improved without special treatment. Pregnant women had no major complications such as cardiac failure, abortion and death. (5) Chromosome karyotype analysis and microarray analysis of amniotic fluid was retained during the operation. No typical chromosome abnormality or other abnormal genetic diagnosis was found. Conclusions: FPV colud be used as an effective intervention measure to promote the development of right ventricle in HRHS fetuses. The scientific management of multidisciplinary professional technical team in perioperative period is particularly important to ensure the success of FPV and the safety of pregnant women and fetuses.

Breaking Earth's shell into a global plate network.

The initiation mechanism of Earth's plate tectonic cooling system remains uncertain. A growing consensus suggests that multi-plate tectonics was preceded by cooling through a single-plate lithosphere, but models for how this lithosphere was first broken into plates have not converged on a mechanism or a typical early plate scale. A commonality among prior efforts is the use of continuum mechanics approximations to evaluate this solid mechanics problem. Here we use 3D spherical shell models to demonstrate a self-organized fracture mechanism analogous to thermal expansion-driven lithospheric uplift, in which globe-spanning rifting occurs as a consequence of horizontal extension. Resultant fracture spacing is a function of lithospheric thickness and rheology, wherein geometrically-regular, polygonal-shaped tessellation is an energetically favored solution because it minimizes total crack length. Therefore, warming of the early lithosphere itself-as anticipated by previous studies-should lead to failure, propagating fractures, and the conditions necessary for the onset of multi-plate tectonics.

Strengthened antioxidant capacity improves photosynthesis by regulating stomatal aperture and ribulose-1,5-bisphosphate carboxylase/oxygenase activity.

ABA is important for plant growth and development; however, it also inhibits photosynthesis by regulating the stomatal aperture and ribulose-1,5-bisphosphate carboxylase/oxygenase activity. Noteworthy, this negative effect can be alleviated by antioxidants including ascorbic acid (AsA) and catalase (CAT), but the underlying mechanism remains unclear. Two rice cultivars, Zhefu802 (recurrent parent) and its near-isogenic line, fgl were selected and planted in a greenhouse with 30/24 °C (day/night) under natural sunlight conditions. Compared to fgl, Zhefu802 had significantly lower net photosynthetic rate (PN) and stomatal conductance (Cond) as well as significantly higher ABA and H2O2 contents. However, AsA and CAT increased PN, Cond, and stomatal aperture, which decreased H2O2 and malondialdehyde (MDA) levels. In this process, AsA and CAT significantly increased the ribulose-1,5-bisphosphate carboxylase activity, while they strongly decreased the ribulose-1,5-bisphosphate oxygenase activity, and finally caused an obvious decrease in the ratio of photorespiration (Pr) to PN. Additionally, AsA and CAT significantly increased the expression levels of RbcS and RbcL genes of leaves, while H2O2 significantly decreased them, especially the RbcS gene. In summary, the removal of H2O2 by AsA and CAT can improve the leaf photosynthesis by alleviating the inhibition on the stomatal conductance and ribulose-1,5-bisphosphate carboxylase capacity caused by ABA.

Activation of the NLRP3 and AIM2 inflammasomes in a mouse model of Schistosoma mansoni infection.

Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.

Ligustilide, a major bioactive component of Angelica sinensis, promotes bone formation via the GPR30/EGFR pathway.

Angelica sinensis (Oliv.) Diels is a widely-used traditional Chinese herbal medicine in treating osteoporosis. Ligustilide (LIG) is the main component of A. sinensis and is considered to be the most effective biologically active ingredient in this plant. LIG has been found to have multiple pharmacological activities, such as anti-atherosclerosis, neuroprotection, anticancer, anti-inflammatory and analgesic. However, little is known regarding its anti-osteoporotic effects. The aims of this study were to investigate any protective effect of LIG on bone formation. The results showed that LIG significantly ameliorated inhibition of bone formation in zebrafish caused by prednisolone. LIG promoted osteoblast differentiation, including that of the pre-osteoblastic cell line MC3T3-E1 and bone marrow mesenchymal stem cells. LIG greatly improved the viability of MC3T3-E1 cells exposed to H2O2, attenuated H2O2-induced apoptosis and increased the expression of Bcl-2. Furthermore, LIG treatment lead to marked activation of phosphorylated EGFR and ERK1/2. These effects could be obviously inhibited by blocking GPR30 signaling with the specific inhibitor G15. Collectively, the results reveal that GPR30 is a positive switch for LIG to increase bone formation via regulation of EGFR, and these results provide evidence for the potential of LIG to treat osteoporosis.