Integrated analysis of intestinal microbiota and transcriptome reveals that a coordinated interaction of the endocrine, immune system and gut microbiota response to heat stress in Litopenaeus vannamei.

Due to the ongoing global warming, the risk of heatwaves in the oceans is continuously increasing while our understanding of the physiological response of Litopenaeus vannamei under extreme temperature conditions remains limited. Therefore, this study aimed to evaluate the physiological responses of L. vannamei under heat stress. Our results indicated that as temperature rose, the structure of intestinal and hepatopancreatic tissues was damaged sequentially. Activity of immune-related enzymes (acid phosphatase/alkaline phosphatase) initially increased before decreased, while antioxidant enzymes (superoxide dismutase and glutathione-S transferase) activity and malondialdehyde content increased with rising temperature. In addition, the total antioxidant capacity decreased with rising temperature. With the rising temperature, there was a significant increase in the expression of caspase-3, heat shock protein 70, lipopolysaccharide-induced tumor necrosis factor-α, transcriptional enhanced associate domain and yorkie in intestinal and hepatopancreatic tissues. Following heat stress, the number of potentially beneficial bacteria (Rhodobacteraceae and Gemmonbacter) increased which maintain balance and promote vitamin synthesis. Intestinal transcriptome analysis revealed 852 differentially expressed genes in the heat stress group compared with the control group. KEGG functional annotation results showed that the endocrine system was the most abundant in Organismal systems followed by the immune system. These results indicated that heat stress leads to tissue damage in shrimp, however the shrimp may respond to stress through a coordinated interaction strategy of the endocrine system, immune system and gut microbiota. This study revealed the response mechanism of L. vannamei to acute heat stress and potentially provided a theoretical foundation for future research on shrimp environmental adaptations.

CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.

Y chromosome polymorphisms contribute to an increased risk of non-obstructive azoospermia: a retrospective study of 32,055 Chinese men.

PURPOSE: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.

Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans.

Oligo-astheno-teratozoospermia (OAT), which is a common cause of male infertility, can be caused by genetic factors. This study reports on a case of a male patient suffering from infertility concomitant with OAT. Whole-exome sequencing (WES) confirmed the presence of a homozygous variant (NM_003462: c.464-1G > A) in the DNALI1 gene via Sanger sequencing. Immunofluorescence staining demonstrated that the DNALI1 signal was nearly undetectable in the patient's sperm. Bioinformatics analysis revealed that this mutation could reverse the splicing of the exon 4 acceptor splice site. A minigene experiment was performed to verify the mutation and the results confirmed that the mutation disrupted the splicing. Our findings show that this rare mutation in DNALI1 contributes to male infertility and OAT in humans, thereby expanding our understanding of the causes and pathogenesis of male infertility. This knowledge facilitates genetic counseling, clinical diagnosis, and therapeutic development of male infertility.

Are economic policy uncertainty and carbon futures price interacting? Evidence from the European Union.

This paper investigates the dynamic interplay between economic policy uncertainty and the carbon futures market within the context of global low-carbon development. The study utilizes a comprehensive dataset spanning 2005 to 2023, including daily observations of economic policy uncertainty (EPU) and carbon future prices (EUAP) in the European Union. Bootstrap subsample rolling window Granger causality tests are employed to examine the interrelationship between EPU and EUAP, providing robust and time-varying causal insights. The findings reveal the adverse impact of EPU on EUAP, highlighting that the volatility associated with economic policy uncertainty can serve as a predictive factor for carbon future prices. On the other hand, the EUAP exhibits a negative influence on the uncertainty of economic policy, indicating that the economic situation in Europe can be observed through the carbon future market. The findings presented in this study are in line with the underlying theoretical model of policy uncertainty and future prices. Considering the complex economic environment and the influence exerted by COVID-19, exploring the link between EPU and EUAP is crucial for informing investors' decision-making and guiding the development of policy to enhance carbon market efficiency and promote a low-carbon economy.

Re-assessment of the close relationship between serum FSH levels and semen quality: a retrospective cohort study of 11,929 Chinese men.

PURPOSE: To establish a medically valuable normal reference interval of follicle-stimulating hormone (FSH) levels in males with normal semen and to assess the predictive value of FSH in males exhibiting semen abnormalities. METHODS: The study involved male patients who underwent their initial serum sex hormone test and semen test between October 2013 and June 2023. The reference interval was identified as the 95% confidence interval (CI) of FSH values in the patients with normal semen parameters. Then, in the total study population, receiver operating characteristic (ROC) curves were performed to evaluate the discriminatory ability of FSH for oligozoospermia and non-obstructive azoospermia (NOA). Besides, multivariable logistic regression was performed to investigate the association of FSH with oligozoospermia and NOA adjusted by age. RESULTS: A total of 11,929 patients were finally enrolled in the study. The normal reference interval of FSH ranged from 1.70 IU/L to 7.60 IU/L (median: 3.98 IU/L) based on 4595 patients with normal semen routine parameters. In the total patients, ROC curves showed FSH to have a "fair" discriminatory ability for oligozoospermia (area under receiver operating characteristic curve (AUC) 0.747, threshold 7.32 IU/L, accuracy 0.734, positive predictive value (PPV) 0.754, negative predictive value (NPV) 0.726), while ROC curves showed FSH to have a "excellent" discriminatory ability for NOA (AUC: 0.921, threshold 10.18 IU/L, accuracy 0.903, PPV 0.593, NPV 0.972). Besides, multivariable logistic regression showed that FSH ≥ 7.32 IU/L was associated with a 8.51-fold increase in the risk of oligozoospermia adjusted by age, while FSH ≥ 10.18 IU/L was associated with a 38.93-fold increase in the risk of NOA. CONCLUSIONS: Our findings indicated that the reference interval for FSH in males with normal semen was 1.70-7.60 IU/L and found that FSH was capable of effectively discerning oligospermia and NOA.

X-linked RBBP7 mutation causes maturation arrest and testicular tumors.

Maturation arrest (MA) is a subtype of non-obstructive azoospermia, and male infertility is a known risk factor for testicular tumors. However, the genetic basis for many affected individuals remains unknown. Here, we identified a deleterious hemizygous variant of X-linked retinoblastoma-binding protein 7 (RBBP7) as a potential key cause of MA, which was also found to be associated with the development of Leydig cell tumors. This mutation resulted in premature protein translation termination, affecting the sixth WD40 domain of the RBBP7 and the interaction of the mutated RBBP7 with histone H4. Decreased BRCA1 and increased γH2AX were observed in the proband. In mouse spermatogonial and pachytene spermatocyte-derived cells, deprivation of rbbp7 led to cell cycle arrest and apoptosis. In Drosophila, knockdown of RBBP7/Caf1-55 in germ cells resulted in complete absence of germ cells and reduced testis size, whereas knockdown of RBBP7/Caf1-55 in cyst cells resulted in hyperproliferative testicular cells. Interestingly, male infertility caused by Caf1-55 deficiency was rescued by ectopic expression of wild-type human RBBP7 but not mutant variants, suggesting the importance of RBBP7 in spermatogenesis. Our study provides insights into the mechanisms underlying the co-occurrence of MA and testicular tumors and may pave the way for innovative genetic diagnostics of these 2 diseases.

Green bonds and US shale gas prices: Evidence from a novel time-varying causality.

This paper provides a new perspective on the green bond market (measured by GBI) and the US shale gas price (measured by SGPI). The leading method for testing the mutual influence between GBI and SGPI, the bootstrap subsample rolling causality test, is a novel application of research in the green bond market. The results of the novel time-varying causality test indicate that SGPI has both positive and negative effects on GBI. Based on the positive reaction of GBI, a spike in SGPI fueled greater demand for green projects, which accelerated the increase in GBI. However, this view cannot be confirmed by the negative effect due to the energy crisis. This outcome is consistent with the general equilibrium model, which underlines a certain impact of SGPI on GBI. Furthermore, the positive impact of GBI on SGPI indicates that shale gas prices can be predicted from the green bond market. Understanding the nexus between SGPI and the GBI is of practical significance for bond issuers, regulators, and investors.

Changes in HER2 status and survival outcomes in patients with non-pathological complete response after neoadjuvant targeted treatment.

To study the changes in human epidermal growth factor receptor 2 (HER2) expression in patients with HER2-positive breast cancer before and after neoadjuvant treatment. The clinicopathologic data of 499 patients with HER2-positive breast cancer who completed neoadjuvant treatment and surgery at the Fourth Hospital of Hebei Medical University from 2018 to 2021 were retrospectively analyzed. According to the new adjuvant regimen, 298 patients were divided into the trastuzumab + pertuzumab combined chemotherapy group (dual target group), and 201 patients were divided into the trastuzumab combined chemotherapy group (single target group).The effect of different neoadjuvant regimens on HER2 status was analyzed by comparing HER2 expression before and after treatment. A total of 255 of 499 neoadjuvant patients with HER2-positive breast cancer achieved a pathological complete response (pCR). pCR was achieved in 60.07% (179/298) of the dual target group and 37.81% (76/201) of the single target group, and the difference was statistically significant (χ² = 23.795, P < .001). Among 244 cases of HER2-positive breast cancer that did not reach pCR (non-pCR), there was a certain negative conversion rate of HER2 expression after neoadjuvant treatment, and the overall negative conversion rate was 13.11% (32/244). The negative conversion rates of the dual target group was 17.65% (21/119) and single target group was 8.80% (11/125), (χ² = 4.188, P = .041). The DFS of 499 patients in the pCR group was 98.43% (251/255), which was significantly higher than that in the non-pCR group 92.21% (225/244), (χ² = 8.536, P = .003). Only 2 (0.20%) of 32 patients with negative HER2 had recurrence and metastasis. Neoadjuvant treatment had an effect on the expression status of HER2, especially in the dual target group. For patients with negative HER2, the optimal treatment strategy remains to be explored, but continued anti-HER2 treatment is still recommended.

DMSO-promoted direct δ-selective arylation of p-quinone methenylpiperidine bearinides to generate fuchsones under metal-free conditions by employing p-QMs themselves or substituted phenols as aryl sources.

Fuchsones have wide applications in modern society. Present methods for generating fuchsones have many disadvantages and there are significant limitations for further exploration of fuchsone applications. Herein, we describe a DMSO-promoted direct δ-selective arylation of p-QMs to synthesize symmetrical and unsymmetrical fuchsones under metal-free conditions by employing p-QMs themselves or substituted phenols as aryl sources. As unprecedented methods, these novel strategies present a great advantage and significance for further exploration of fuchsones and the development of new applications.

First report of Colletotrichum siamense as a causal agent of anthracnose on wax apple (Syzygium samarangense) in China.

Wax apple (Syzygium samarangense) is an important fruit tree widely cultivated in China. Yield losses are usually serious due to different diseases among which anthracnose (Colletotrichum spp.) is one of the most damaging (He et al, 2019). This disease was found in Yunnan, China and an average incidence of 56.7% diseased leaves was recorded in21 orchards surveyed in July2021. The disease lesions on leaves were circular, angular or oval (7.2-15.6 mm), with whitish center and brown outer area surrounded by a yellow halo; irregular spots or blight areas formed later. It can also infect fruits forming pale-brown, circular and sunken spots before harvest and rot of stored fruits. Diseased leaves were sampled from orchards in Ximeng (N117.78oE39.89o) and Ninger (E101.04oN23.05o) counties of Yunnan for fungal isolation; three and five pure isolates were recovered from Ximeng (LWTJ1-LWTJ3) and Ninger (LB4-LB8) samples, respectively, by plating disinfested tissue (surface-sterilized with 2% NaClO3) on potato dextrose agar (PDA) followed by hyphal tip purification and incubation at 25oC. Two repeated tests following Koch's postulates were conducted to verify pathogenicity of the eight isolates. In each test, three healthy seedlings per isolate were sprayed with conidia suspenson (2.26×105cfu/mL) until runoff from leaves while control plants were sprayed with sterile water. The plants were kept in the dark at RH100 for 24 h in a black box and then in a growth chamber (28oC, RH>90% and lighting 12h/d). Detached fruits were inoculated with mycelial discs on the puncture-wound surface. Anthracnose symptoms developed on all seedlings and fruits inoculated with LWTJ2 or LB4 isolates, which were re-isolated from lesions of inoculated leaf/fruit, completing Koch's postulates. Control plants were healthy and symptomless. LWTJ2 and LB4 isolates were morphologically the same: the colonies on PDA were circular, pale-white, with cottony surface and readily forming orange conidium masses. The hyphae were hyaline, septate, branched mostly in near right angles. The conidia were hyaline, one-celled, smooth-walled, cylindrical with round ends, 9.8-17.5 (av.13.8) µm×4.4-6.5 (5.6) µm. The teleomorph was not observed in culture or on orchard trees. The morphological characters were consistent with those of C. siamense described by Weir et al (2012). The internal transcribed spacer region (ITS) was amplified from the two isolates by PCR and sequenced (1990) and were 545 bp in length (OL963924 & OL413460). BLAST analysis showed that both were 100% identical and they shared 99.08% identity with C. siamense WZ-365 from the ITS region (MN856443).The Tub2 (788 bp, ON637119) and Cal (768 bp, ON622249) genes (Weir et al, 2012) of LB4 were also obtained and they shared closest identity (99.45% & 100%) with those of C. siamense WZ-365 as well. Phylogenetic tree (neighbor-joining) analysis of the concatenated sequence of ITS, Tub2 and Cal genes of LB4 and those of related Colletotrichum spp. showed that LB4 clustered IN the same end-branch with C. siamense ICMP18578 (Bootstrap sup. = 98%). Thus, C. siamense was identified as the pathogen of wax apple anthracnose in Yunnan. It caused anthracnose on other crops as oranges and cacao (Azad et al, 2020). Also, C. fructicola and C. syzygicola were identified as pathogens of wax apple anthracnose in Thailand (Al-Obaidi et al, 2017). To our knowledge, this is the first report of C. siamense causing wax apple anthracnose in China.

How does ESG performance affect stock returns? Empirical evidence from listed companies in China.

With the increasing attention to sustainable development, environmental, social, and corporate governance (ESG) investment has become an important vehicle for achieving carbon neutrality worldwide. In this paper, the impact of ESG performance on stock returns and the transmission mechanism are explored. A fixed effect model based on a panel unbalanced data of listed companies in China from 2011 to 2020 is selected for the empirical analysis. The results show that ESG performance of listed companies in China positively impacts stock returns. However, by distinguishing the ownership nature and region to which listed companies belong, this study finds that the relationship between ESG performance and stock returns is particularly significant for non-state-owned companies and those in the eastern region. Further, based on stakeholder theory, financial performance and corporate innovation ability are embedded into the relationship between ESG performance and stock returns. Both financial performance and corporate innovation ability play partial mediating roles in the correlation between ESG performance and stock returns. In addition, the relationship between ESG performance and corporate innovation ability is non-linear. This paper provides insight for emerging markets into cultivating the value investment concept of investors and improving the ESG information disclosure system.

Control and regulation of the performance of fullerene-based dye-sensitized solar cells with a D-D-A structure by external electric fields.

We investigated the modulating effect of an electric field (Fext) on the photovoltaic properties of triphenylamine-based sensitizers with a D-D-A structure and compared the photovoltaic parameters at different electric field intensities. The results show that Fext can effectively adjust the photoelectric properties of the molecule. From the change of the parameters that measures the degree of electron delocalization, it can be seen that the Fext can effectively strengthen the electronic communication and promote the charge transfer process within the molecule. And the dye molecule under a strong Fext has a narrower energy gap, more favorable injection, regeneration driving force and a larger conduction band energy level shift, which ensures that the dye molecule can exhibit larger Voc and Jsc under a strong Fext. The results of calculations on the photovoltaic parameters of dye molecules show that dye molecules can exhibit better photovoltaic performance under the action of Fext, which provides beneficial predictions and prospects for the development of highly efficient DSSCs.

Hsa_circ_0002496 promotes the growth, angiogenesis, and stemness of breast cancer cells via miR-433-3p/YWHAZ cascade.

BACKGROUND: Breast cancer (BC) has been studied more and more in modern medicine. Circ_0002496 has established a critical role in BC. MiR-433-3p can exert important activity in cancer. YWHAZ can participate in BC development, but the targeting relationship among the three variables and its influence on the related process of BC are not clear. METHODS: RT-qPCR was used to analyze circ_0002496, miR-433-3p, and YWHAZ expression. Immunoblotting was used to analyze YWHAZ, Bax, Bcl-2, and PI3K/AKT-related proteins. RNase R assay was used to verify the ring structure of circ_0002496. Cell phenotypes were tested by Cell Counting Kit 8, EdU, sphere formation, tube formation, and flow cytometry assays. RESULTS: Circ_0002496 was enhanced and MiR-433-3p was downregulated in BC, while the expression of YWHAZ was higher in BC. Circ_0002496 targeted miR-433-3p and miR-433-3p targeted YWHAZ in BC cells. Depletion of circ_0002496 influenced the BC process, but miR-433-3p inhibitor reversed the impact of si-circ_0002496 on the BC process. Re-expression of YWHAZ weakened the influence of miR-433-3p on the BC process. Depletion of circ_0002496 could astrict tumor growth in vivo. Moreover, the circ_0002496/miR-433-3p/YWHAZ axis mediated the activation of the PI3K/AKT signaling pathway. CONCLUSION: Circ_0002496 participated in the malignant procession of BC by miR-433-3p/YWHAZ regulation cascade.

Effects of major depression and bipolar disorder on erectile dysfunction: a two-sample mendelian randomization study.

BACKGROUND AND AIMS: There are currently no clear conclusions about whether major depression (MD) and bipolar disorder (BD) increase the risk of erectile dysfunction (ED). In our study, we used a Mendelian randomization (MR) analysis to discover the causal associations between MD, BD and ED. METHODS: We got single-nucleotide polymorphisms (SNPs) related to MD, BD and ED from the MRC IEU Open genome-wide association study (GWAS) datasets. After a series of selection, SNPs left were selected as instrumental variables (IVs) of MD and BD for the following MR test to evaluate the relationship of genetically predicted MD or BD with the incidence of ED. Among them, we used the random-effects inverse-variance weighted (IVW) method as the main analysis. Finally, sensitivity analyses were further performed using Cochran's Q test, funnel plots, MR-Egger regression, Leave-one-out method and MR- pleiotropy residual sum and outlier (PRESSO). RESULTS: Genetically-predicted MD was causally related to the incidence of ED in the IVW methods (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.19-1.96; p = 0.001), while no causal impact of BD on the risk of ED (OR = 0.95, 95% CI 0.87-1.04; p = 0.306). The results of sensitivity analyses supported our conclusion, and no directional pleiotropy were found. CONCLUSION: The findings of this research found evidence of a causal relationship between MD and ED. However, we did not find a causal relationship between BD and ED in European populations.

Protective effect and mechanism of Polygonatum kingianum against hypoxia-induced injury.

Background: Hypoxia is an essential cause of fatigue and aging, and is associated with the occurrence and development of many diseases. Polygonatum kingianum (PK) is a deficiency-nourishing Chinese herbal medicine utilized as both medicine and food, and it has long been used to ameliorate human conditions associated with fatigue and aging over 2000 years in China. PK is an important genuine-medicinal-materials cultivated in Yunnan, China, and is used by the Bai, Wa, and Zhuang nationalities as a traditional medicine for enhancing immunity, anti-fatigue, and anti-aging, while the preventive effect of PK on hypoxia-induced injury and the underlying mechanism are indefinite. Aim of the study: The present study aimed to evaluate the anti-hypoxia efficacy and understand the corresponding mechanism of PK water extract. Materials and methods: The main active ingredients and targets of PK were predicted using network pharmacology, and the anti-hypoxia activities of Gracillin and Liquiritigenin were verified by in vitro experiments. The pharmacodynamic experiments were conducted to evaluate the major signal pathways of PK for detecting anti-hypoxia activity. Results: Fifty active ingredients and 371 potential targets were screened by network pharmacology, then, we confirmed that Gracillin and Liquiritigenin were the main active components of PK to exert anti-hypoxia effect in vitro. The pharmacodynamic experiments revealed that PK enhanced the extension rate of the survival time (ERST) and regulated the targets-related biochemical parameters of rats under hypoxia, showing significant anti-hypoxia effects on rats. Conclusion: The network pharmacology results suggested that PK exerts its anti-hypoxia effect through a multi-component and multi-target manner. Simultaneously, we also observed that Gracillin (saponins) and Liquiritigenin (flavonoids) are the main active components of PK to play a role in anti-hypoxia. The anti-hypoxia effect of PK could be associated with scavenging excess free radicals, maintaining the activities of antioxidant enzymes, and inhibiting oxidative stress due to lipid peroxidation. These findings provide insight into the Polygonatum kingianum as promising medicines or healthcare products for preventing and treating hypoxia.

Comprehensive analysis of the PTPN13 expression and its clinical implication in breast cancer.

Protein tyrosine phosphatases non-receptor 13 (PTPN13) could be a potential biomarker in breast cancer (BRCA), but its genetic variation and biological significance in BRCA remain undefined. Hereon, we comprehensively investigated the clinical implication of PTPN13 expression/gene mutation in BRCA. In our study, a total of 14 cases of triple-negative breast cancers (TNBC) treated with neoadjuvant therapy were enrolled, and post-operation TNBC tissues were collected for next-generation sequencing (NGS) analysis (422 genes including PTPN13). According to the disease-free survival (DFS) time, 14 TNBC patients were divided into Group A (long-DFS) and Group B (short-DFS). The NGS data displayed that the overall mutation rate of PTPN13 was 28.57% as the third highest mutated gene, and PTPN13 mutations appeared only in Group B with short-DFS. In addition, The Cancer Genome Atlas (TCGA) database demonstrated that PTPN13 was lower expressed in BRCA than in normal breast tissues. However, PTPN13 high expression was identified to be related to a favorable prognosis in BRCA using data from the Kaplan-Meier plotter. Moreover, Gene Set Enrichment Analysis (GSEA) revealed that PTPN13 is potentially involved in interferon signaling, JAK/STAT signaling, Wnt/ß-catenin signaling, PTEN pathway, and MAPK6/MAPK4 signaling in BRCA. This study provided evidence that PTPN13 might be a tumor suppressor gene and a potential molecular target for BRCA, and genetic mutation and/or low expression of PTPN13 predicted an unfavorable prognosis in BRCA. The anticancer effect and molecular mechanism of PTPN13 in BRCA may be associated with some tumor-related signaling pathways.

Toxic effects of glyphosate on histopathology and intestinal microflora of juvenile Litopenaeus vannamei.

Glyphosate is a widely used broad-spectrum herbicide, its pollution to the surrounding conditions can't be ignored. It has been reported that glyphosate has poisonous impacts on aquatic animals. In this study, juvenile Litopenaeus vannamei (L. vannamei) was exposed to glyphosate, and the lethal concentration 50 (LC50) of glyphosate to juvenile L. vannamei for 48 h was 47.6 mg/L. The histological analysis for intestine and hepatopancreas and the intestinal microorganisms of L. vannamei were evaluated after 48 h of exposure to glyphosate with LC50. The histological analysis results showed that the lumen of hepatic tubules was diffused and deformed, the hepatic tubules were ruptured and intestinal villi were fallen off seriously after exposure to glyphosate for 48 h Moreover, the intestinal microbial composition and structure of L. vannamei were changed, with the abundance of Alphaproteobacteria increased significantly. The abundance of Rhodobacteraceae, Vibrio and Legionella increased, but there was no significant difference. The abundance of Bacillus, Paraburkholderia, Enhydrobacter, Comamonas and Alkanindiges decreased significantly. However, the homeostasis of intestinal microorganisms was destroyed. Phenotypic prediction of the two groups of microorganisms revealed a significant increase in the abundance of Facultatively Anaerobic in the glyphosate challenged group. This study suggested that hepatopancreas and intestinal tissue of L. vannamei were seriously damaged after 48 h of exposure to glyphosate with LC50, and intestinal microbial homeostasis was disrupted.

A disease-targeted picture book for children with Henoch-Schonlein purpura nephritis: A quasi-experimental study.

BACKGROUND: Children with Henoch-Schonlein purpura nephritis are frequently burdened with psychological problems besides disease treatment and adherence. Currently, there is a shortage of appropriate and effective educational materials to facilitate physical and psychological recovery. OBJECTIVES: To examine a picture book for the effectiveness of disease-related knowledge, coping strategies, resilience, quality of life and depressive symptoms in children with Henoch-Schonlein purpura nephritis in China. DESIGN: A quasi-experimental design with repeated measures was adopted. The control group received standard care. The intervention group received the standard care plus a free picture book. This disease-specific picture book narrated the story of two rabbits diagnosed with Henoch-Schonlein purpura nephritis who underwent a series of examinations, faced difficulties taking medication, and eventually recovered. PARTICIPANTS: The study recruited 60 children diagnosed with Henoch-Schonlein purpura nephritis. MEASUREMENTS: Disease-related knowledge, resilience, coping strategies, depression and paediatric quality of life were measured at baseline, the third day, the first month and the third month after recruitment. The acceptability of the picture book was evaluated at the last data-collection point. RESULTS: The data showed that children in the intervention group demonstrated higher levels of knowledge (p < 0.001), less usage of emotional coping strategies (p = 0.003), reduced depressive symptoms (p = 0.003), improved psychological resilience (p < 0.001), and better quality of life (p < 0.046) than those in the control group in the third month. Most children (83.3%) in the intervention group were satisfied with the picture book. CONCLUSIONS: The targeted picture book is an effective educational tool for improving clinical outcomes and was highly accepted by children.

Micro/nano-modified titanium surfaces accelerate osseointegration via Rab7-dependent mitophagy.

To achieve rapid and successful osseointegration of titanium (Ti) implants, the underlying mechanisms of surface modification-mediated bone metabolism need to be clarified. Given that the microenvironment surrounding Ti implants may be altered after implant insertion, mitophagy as a key control system for cellular homeostasis is most likely to regulate osseointegration. Recent findings suggest that PTEN-induced putative kinase 1 (Pink1)/Parkin-mediated mitophagy plays a key role in bone metabolism. Since the micro/nano-modified surfaces of Ti implants have been widely appreciated for osseointegration acceleration, we used two common micro/nano-modified techniques and demonstrated elevations of both the osteo-differentiation potential and Pink1/Parkin pathway of osteoblasts. Moreover, the Pink1/Parkin pathway exhibited an upward trend during osteoblast differentiation. However, when osteoblasts were treated with CCCP, a Pink1/Parkin inducer, the osteo-differentiation potential decreased. Our further study showed that the small GTPase Rab7, which was inhibited by CCCP, was essential for the Pink1/Parkin pathway. Upon Pink1 or Rab7 knockdown, the pro-osteogenic effect of micro/nano-modified Ti surfaces was significantly weakened. The present results demonstrated that Rab7 activation was essential for active mitophagy and osteogenesis. In addition, Rab7 was confirmed to mediate the process of autophagosome formation. Our findings provide novel insights into new targets for osseointegration promotion, regardless of Ti surface characteristics.