bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of atosiban for repeated embryo implantation failure: A systematic review and meta-analysis
Authors: Wang Ruxin , Huang Haixia , Tan Yong , Xia Guicheng
Published: March 2023

Background

Repeated embryo implantation failure (RIF) posed a significant challenge in assisted reproduction. Evidence of its therapeutic effectiveness including atosiban used around embryo transfer to improve pregnancy outcomes in RIF patients undergoing in vitro fertilization-embryo transfer (IVF-ET) remained inconsistent. This study aimed to explore the efficacy of atosiban on pregnancy outcomes of patients with RIF who received IVF-ET.

Methods

The research was designed using the PICOS format. A systematic search of four English databases, PubMed, EMBASE, Web of Science, Cochrane Library, and one Chinse database, China National Knowledge Infrastructure (CNKI) was conducted. The time range was from inception to December 10, 2022. Then trials comparing the efficacy of atosiban and control group on pregnancy outcomes in RIF patients who receive IVF-ET were included. Subgroup analysis and sensitivity analysis were performed to reduce the influence of heterogeneity between included studies. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The main outcome measure was clinical pregnancy rate (CPR). For the analyses, StataMP 17.0 (Stata Corporation, USA) was used.

Results

Two prospective randomized controlled trials (RCTs), one prospective cohort study and four retrospective cohort studies were included. Our results showed that atosiban was associated with higher clinical pregnancy rate (RR=1.54, 95% CI: 1.365–1.735, P < 0.001, I2 = 0.0%). The results of subgroup analysis based on study types (prospective randomized controlled clinical trial, retrospective cohort study and prospective cohort study) showed that in all types of studies, CPR of atosiban group was significantly higher than controlled group. The results of subgroup analysis based upon the diagnostic criteria of number of previous embryo transfer failures showed that the intervention of atosiban improved the CPR whether in participants with 2 previous ET failures or in participants with 3 previous ET failures. Nevertheless, the incidence of ectopic pregnancy, multiple pregnancy, and miscarriages were not significantly different between the case and control groups.

Conclusion

For women who are undergoing IVF-ET and have experienced repeated embryo implantation failure, atosiban may be an important factor in enhancing pregnancy outcomes. To confirm this conclusion, more thorough, prospective randomized controlled studies of sizable sample sizes with well design are required.
Biphasic expression of thyroid hormone receptor TRβ1 in mammalian retina and anterior ocular tissues
Authors: Ng Lily , Liu Hong , Liu Ye , Forrest Douglas
Published: March 2023

The retina is increasingly recognized as a target of thyroid hormone. We previously reported critical functions for thyroid hormone receptor TRβ2, encoded by Thrb, in cones, the photoreceptors that mediate color vision. TRβ1, another Thrb receptor isoform, is widely expressed in other tissues but little studied in the retina. Here, we investigate these N-terminal isoforms by RNA-sequencing analysis and reveal a striking biphasic profile for TRβ1 in mouse and human retina. In contrast to the early TRβ2 peak, TRβ1 peaks later during retinal maturation or later differentiation of human retinal organoids. This switch in receptor expression profiles was confirmed using lacZ reporter mice. TRβ1 localized in cones, amacrine cells and ganglion cells in contrast to the restricted expression of TRβ2 in cones. Intriguingly, TRβ1 was also detected in the retinal pigmented epithelium and in anterior structures in the ciliary margin zone, ciliary body and iris, suggesting novel functions in non-retinal eye tissues. Although TRβ1 was detected in cones, TRβ1-knockout mice displayed only minor changes in opsin photopigment expression and normal electroretinogram responses. Our results suggest that strikingly different temporal and cell-specific controls over TRβ1 and TRβ2 expression may underlie thyroid hormone actions in a range of ocular cell types. The TRβ1 expression pattern suggests novel functions in retinal and non-neural ocular tissues.
Pathways for an island energy transition under climate change: The case of Chongming Island, China
Authors: Song Xuemei , Chen Zhujun
Published: March 2023

The normal operation of the energy system is related to the security and stability of the region and even the country. Compared with inland areas, islands can become a precedent for building a low-carbon and zero-carbon society due to geographic advantage. However, they also have to deal with more vulnerable energy systems. Taking Chongming Island as a case, this paper discusses the necessity of energy transformation from external, internal, and geographic causes, investigates the possible path of resilient energy transformation for islands, and puts forward a series of policy recommendations together with possible ways toward resilient energy transition.
Good times bad times — Unfavorable breeding conditions, more than divorce, lead to increased parental effort and reduced physiological condition of northern gannets
Authors: Pelletier David , Blier Pierre , Vézina François , Guillemette Magella
Published: March 2023

Decreased productivity in long-lived bird species is linked to prey depletion in marine ecosystems. Seabirds, however, exhibit behavioral flexibility at individual level to prevent this outcome. One such strategy to alleviate any impact on fitness would be to divorce from their partners. Although changing mates and increasing foraging effort have been shown to increase or maintain reproductive success, how the behavioral flexibility affects fundamental physiological parameters remains to be elucidated. Here, we compared physiological components (nutritional status, muscle damage and oxidative stress) of northern gannets (Morus bassanus) in relation to their partnership status and foraging effort. Specifically, we used a cross-sectional data set (at the population level) of three contrasted years to compare retained and changed mates. We predicted that mate change is a stressful event with impacts on health condition and those effects are higher during unfavorable years with food depletion. Our study showed that gannets changing mate increase parental effort only during years of low food abundance, with consequences on health condition (increased body mass loss, higher protein catabolism and higher oxidative damage during chick rearing period). Ultimately, our study suggests that partnership decision is not likely to reduce the long-term quality and the fitness of parents. Reproduction during harsh conditions would however likely be one of the primary causes of individual quality loss and fitness decline in this long-lived bird species.
Ecosystem service assessment under ecological restoration programs: A systematic review of studies from China
Authors: Liu Junyan , Du Jie , Zhang Chenfeng , Zhang Jindong , Yang Hongbo , Donald Marion L. , Wu Yan , Dong Tingfa
Published: March 2023

With a growing body of literature on the topic of ecosystem service (ES), there is an urgent need to summarize ES research in the context of ecological restoration programs (ERPs) in China and identify knowledge gaps for future directions. We conducted a systematic literature review of articles to examine the use of ES approaches for ERP assessments. Our results showed that previous studies mainly focused on the Shaanxi Province, and more than half of the reviewed studies considered no more than three ES types simultaneously. All ES categories were not covered equally; most of the studies focused on provisioning and regulating services, while cultural services have received little attention. Although regional-scale and short-term assessments dominated the reviewed papers, we suggest that multiple temporal and spatial scales for ERP assessments should be given more attention in future work. Moreover, we highlight that an oversimplified land use/land cover (LULC) categorization scheme may potentially lead to inaccuracies and biases in ESs detection under restoration programs. Based on this review, our findings can guide future ERP assessments by using the ES approach. Meanwhile, given the global LULC change brought by the proliferation of plantations under ERPs, our results are also expected to provide a path forward to assess ESs associated with LULC change globally.
Genetic diagnostic yields of 354 Chinese ASD children with rare mutations by a pipeline of genomic tests
Authors: Zhang Yue , Li Ying , Guo Ruolan , Xu Wenjian , Liu Xuanshi , Zhao Chunlin , Guo Qi , Xu Wenshan , Ni Xin , Hao Chanjuan , Cui Yonghua , Li Wei
Published: March 2023

Purpose: To establish an effective genomic diagnosis pipeline for children with autism spectrum disorder (ASD) for its genetic etiology and intervention.

Methods: A cohort of 354 autism spectrum disorder patients were obtained from Beijing Children’s Hospital, Capital Medical University. Peripheral blood samples of the patients were collected for whole genome sequencing (WGS) and RNA sequencing (RNAseq). Sequencing data analyses were performed for mining the single nucleotide variation (SNV), copy number variation (CNV) and structural variation (SV). Sanger sequencing and quantitative PCR were used to verify the positive results.

Results: Among 354 patients, 9 cases with pathogenic/likely pathogenic copy number variation and 10 cases with pathogenic/likely pathogenic single nucleotide variations were detected, with a total positive rate of 5.3%. Among these 9 copy number variation cases, 5 were de novo and 4 were inherited. Among the 10 de novo single nucleotide variations, 7 were previously unreported. The pathological de novo mutations account for 4.2% in our cohort.

Conclusion: Rare mutations of copy number variations and single nucleotide variations account for a relatively small proportion of autism spectrum disorder children, which can be easily detected by a genomic testing pipeline of combined whole genome sequencing and RNA sequencing. This is important for early etiological diagnosis and precise management of autism spectrum disorder with rare mutations.
Genomic profiling of WRKY transcription factors and functional analysis of CcWRKY7, CcWRKY29, and CcWRKY32 related to protoberberine alkaloids biosynthesis in Coptis chinensis Franch
Authors: Huang Xiaoqiang , Jia An , Huang Tao , Wang Li , Yang Guohua , Zhao Wanli
Published: March 2023

Coptis chinensis Franch. (Huanglian in Chinese) is an important economic crop with medicinal value. Its rhizome has been used as a traditional herbal medicine for thousands of years in Asia. Protoberberine alkaloids, as the main bioactive component of Coptis chinensis, have a series of pharmacological activities. However, the protoberberine alkaloids content of C. chinensis is relatively low. Understanding the molecular mechanisms affecting the transcriptional regulation of protoberberine alkaloids would be crucial to increase their production via metabolic engineering. WRKY, one of the largest plant-specific gene families, regulates plant defense responses via the biosynthesis of specialized metabolites such as alkaloids. Totally, 41 WRKY transcription factors (TFs) related to protoberberine alkaloid biosynthesis were identified in the C. chinensis genome and classified into three groups based on phylogenetic and conserved motif analyses. Three WRKY genes (CcWRKY7, CcWRKY29, and CcWRKY32) may regulate protoberberine alkaloid biosynthesis, as suggested by gene-specific expression patterns, metabolic pathways, phylogenetic, and dual-luciferase analysis. Furthermore, the CcWRKY7, CcWRKY29, and CcWRKY32 proteins were specifically detected in the nucleus via subcellular localization. This study provides a basis for understanding the regulatory mechanisms of protoberberine alkaloid biosynthesis and valuable information for breeding C. chinensis varieties.
Fecal microbiota transfer to treat ulcerative colitis: Medical and legal challenges
Authors: Steube Arndt , Stallhofer Johannes , Stallmach Andreas
Published: March 2023

Ulcerative colitis (UC) is one of the main forms of chronic inflammatory bowel disease; however, despite intensive efforts, its etiology remains unclear. It is generally accepted that disturbances in the gastrointestinal microbiota (“dysbiosis”) contribute to the manifestation and perpetuation of UC. To date, treatment has focused on anti-inflammatory strategies; however, their widespread application is limited by side effects and primary/secondary loss of response. Following the resounding success of fecal microbiota transfer (FMT) to treat Clostridioides difficile infection (CDI), numerous studies have shown that FMT is also effective and safe in UC patients. In this review, we discuss the various modifications (e.g., antibiotic preconditioning, multi-donor concept, extension/intensification of application, long-term therapy, and dietary donor conditioning) that increase the efficacy of FMT. We then describe how the continuous need for healthy donors and the associated medicolegal requirements, limit the large-scale application of FMT. We conclude that FMT will likely be viewed as a transitional technology, which will be superceded by recombinantly produced bioproducts once the therapeutically active substances have been identified.
Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic
Authors: de Sèze Jérôme , Maillart Elisabeth , Gueguen Antoine , Laplaud David A. , Michel Laure , Thouvenot Eric , Zephir Hélène , Zimmer Luc , Biotti Damien , Liblau Roland
Published: March 2023

The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.
Immune activation and exhaustion marker expression on T-cell subsets in ART-treated adolescents and young adults with perinatal HIV-1 infection as correlates of viral persistence
Authors: Huang Yuyang , Dhummakupt Adit , Khetan Priya , Nilles Tricia , Zhou Weiqiang , Mudvari Prakriti , Szewczyk Joseph , Chen Ya Hui , Boritz Eli , Ji Hongkai , Agwu Allison , Persaud Deborah
Published: March 2023

HIV-1 infection in memory CD4+ T cells forms a latent reservoir that is a barrier to cure. Identification of immune biomarkers that correlate with HIV-1 reservoir size may aid with evaluating efficacy of HIV-1 eradication strategies, towards ART-free remission and cure. In adults living with non-perinatal HIV-1, the immune exhaustion marker PD-1 on central memory CD4+ T cells (Tcm) correlates with measures of HIV-1 reservoir size. Immune correlates of HIV-1 are less defined in adolescents and young adults with perinatal HIV-1. With multi-parameter flow cytometry, we examined immune activation (CD69, CD25, HLA-DR), and exhaustion (PD-1, TIGIT, TIM-3 and LAG-3) markers on CD4+ T cell subsets (naïve (Tn), central memory (Tcm), and the combination (Ttem) of transitional (Ttm) and effector memory (Tem) cells, in 10 adolescents and young adults living with perinatal HIV-1 (median age 15.9 years; median duration of virologic suppression 7.0 years), in whom HIV-1 reservoir size was measured with the Intact Proviral HIV-1 DNA Assay (IPDA) and an enhanced Tat/Rev limiting dilution assay (TILDA). RNA-seq was also performed on the unstimulated CD4+ T cells. The median total HIV-1 DNA concentration in memory CD4+ T cells was 211.90 copies per million CD4+ T cells. In the 7 participants with subtype B HIV-1 infection, the median intact proviral DNA load was 7.96 copies per million CD4+ T cells. Levels of HLA-DR and TIGIT on the Ttem were correlated with total HIV-1 DNA (r=0.76, p=0.015) and (r=0.72, p=0.023), respectively, but not with intact proviral load or induced reservoir size. HIV-1 DNA load was also positively correlated with transcriptional clusters associated with HLA-DR expression by RNA-seq. In contrast, PD-1 expression on Tcm was inversely correlated with total HIV-1 DNA (r=-0.67, p=0.039). Reservoir size by IPDA and TILDA were correlated (r=0.81, p=0.036). Thus, in this cohort of youths with long-standing treated perinatal infection, HLA-DR and TIGIT on Ttem were the key correlates of HIV-1 infected cell frequencies by total HIV-1 DNA, and not PD-1. Total HIV-1 DNA was negatively correlated with PD-1 expressing Tcm. These differences in longstanding perinatal HIV-1 infection compared with adult infection requires further study in larger cohorts.
The m6A methylation landscape, molecular characterization and clinical relevance in prostate adenocarcinoma
Authors: Li Chao , Peng Dongyi , Gan Yu , Zhou Lei , Hou Weibin , Wang Bingzhi , Yuan Peng , Xiong Wei , Wang Long
Published: March 2023

Background

Despite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6-methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance.

Methods

Through systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6A-related genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups.

Results

A variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased.

Conclusions

This study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs.
Comparison of neoadjuvant immunotherapy versus routine neoadjuvant therapy for patients with locally advanced esophageal cancer: A systematic review and meta-analysis
Authors: Qin Hao , Liu Futao , Zhang Yaozhong , Liang Yuxiang , Mi Yuan , Yu Fan , Xu Haidi , Li Kuankuan , Lin Chenxi , Li Lei , Tian Ziqiang , Wang Lei
Published: March 2023

Background

The neoadjuvant use of immune checkpoint inhibitor combined with chemotherapy (nICT) or chemoradiotherapy (nICRT) in locally advanced esophageal cancer (EC) is currently an area of active ongoing research. Therefore, we carried out a comprehensive meta-analysis to compare the efficacy and safety of the new strategy with routine neoadjuvant strategy, which included neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT).

Patients and methods

MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library were included. And, all of them were searched for eligible studies between January, 2000 and February, 2023. The pathological complete response (pCR) and major pathological response (MPR) were primary outcome of our study. The second outcome of interest was R0 resection rate. Odds ratio (OR) and associated 95% CI were used as the effect indicators comparing the safety and efficiency of the neoadjuvant immunotherapy with the routine neoadjuvant therapy. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity.

Results

There were eight trials with 652 patients were included in our meta-analysis. The estimated pCR rate was higher in the neoadjuvant immunotherapy group (OR =1.86; 95% CI, 1.25–2.75; I2 = 32.8%, P=0.166). The different results were found in the esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) subgroups, the estimated OR was 2.35 (95%CI, 1.00–2.72; I2 = 30.9%, P=0.215) in the EAC subgroup, and 2.35 (95% CI, 1.20–4.54; I2 = 45.3%, P=0.161) in the ESCC subgroup, respectively. The neoadjuvant immunotherapy also showed the advantage in the MPR rates (OR =2.66; 95% CI, 1.69–4.19; I2 = 24.3%, P=0.252). There was no obvious difference between the neoadjuvant immunotherapy and routine neoadjuvant therapy with respect to surgical resection rate, R0 resection rate, surgical delay rate; while more treatment-related adverse events were observed for the neoadjuvant immunotherapy for pneumonitis/pneumonia (OR=3.46, 95% CI, 1.31–9.16; I2 = 67.3%, P=0.005) and thyroid dysfunction (OR=4.69, 95% CI, 1.53–14.36; I2 = 56.5%, P=0.032).

Conclusion

The pooled correlations indicated that the neoadjuvant immunotherapy (both nICT and nICRT) could significantly increase the rates of pCR and MPR, compared with routine neoadjuvant therapy (both nCT and nCRT) in the treatment of locally advanced EC. The neoadjuvant immunotherapy and routine neoadjuvant therapy were with acceptable toxicity. However, randomized studies with larger groups of patients need to performed to confirm these results.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42020155802.
Glycan masking in vaccine design: Targets, immunogens and applications
Authors: Martina Cristina E. , Crowe James E. , Meiler Jens
Published: March 2023

Glycan masking is a novel technique in reverse vaccinology in which sugar chains (glycans) are added on the surface of immunogen candidates to hide regions of low interest and thus focus the immune system on highly therapeutic epitopes. This shielding strategy is inspired by viruses such as influenza and HIV, which are able to escape the immune system by incorporating additional glycosylation and preventing the binding of therapeutic antibodies. Interestingly, the glycan masking technique is mainly used in vaccine design to fight the same viruses that naturally use glycans to evade the immune system. In this review we report the major successes obtained with the glycan masking technique in epitope-focused vaccine design. We focus on the choice of the target antigen, the strategy for immunogen design and the relevance of the carrier vector to induce a strong immune response. Moreover, we will elucidate the different applications that can be accomplished with glycan masking, such as shifting the immune response from hyper-variable epitopes to more conserved ones, focusing the response on known therapeutic epitopes, broadening the response to different viral strains/sub-types and altering the antigen immunogenicity to elicit higher or lower immune response, as desired.
Ophthalmic immune-related adverse events associated with immune checkpoint inhibitors
Authors: Gan Linyang , Chen Huan , Liu Xiaowei , Zhang Li
Published: March 2023

Purpose

To investigate the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapy and to report the clinical features, management, and outcomes of ophthalmic irAEs.

Methods

We retrospectively reviewed the medical records of patients who received ICI therapy from January 2016 to September 2022 at Peking Union Medical College Hospital and analyzed the incidence of systemic and ophthalmic adverse effects of this therapy.

Results

Of 962 patients, 248 (25.8%) experienced irAEs. The first-year incidences of total irAEs and ophthalmic irAEs were 23.5% and 1.1%. The most common ICI received by the patients was pembrolizumab (373; 38.8%). Nearly half of the patients (477; 49.6%) had lung cancer. Combination therapy was associated with an increased incidence of irAEs without statistical significance. Patients with lung cancer presented with an increased incidence of total irAEs (p = 0.003) and ophthalmic irAEs (p = 0.032). Eleven patients had ophthalmic manifestations, including ophthalmoplegia (6/11), conjunctivitis (3/11), reactive cutaneous capillary endothelial proliferation (RCCEP) (1/11), and orbital inflammation (1/11). Eight patients had concomitant extra-ophthalmic irAEs. Furthermore, ICIs were discontinued in nine patients, and most ophthalmic manifestations were well controlled with topical and systemic steroids. Ten patients were treated with intravenous or oral steroids. However, cancer progression occurred in five out of eleven patients after the interruption of ICIs.

Conclusion

IrAEs are correlated with ICI regimens and underlying neoplasia. In our Chinese cohort, patients have a higher risk of ophthalmoplegia than uveitis. Early recognition and multidisciplinary consultation are crucial for optimal treatment of ophthalmic irAEs.
A new insight into the impact of systemic lupus erythematosus on oocyte and embryo development as well as female fertility
Authors: Mao Ruolin , Wang Xiangfei , Long Rui , Wang Meng , Jin Lei , Zhu Lixia
Published: March 2023

Background

Systemic lupus erythematosus (SLE) is often associated with adverse reproductive outcomes. But it’s currently unclear regarding the role of SLE in oocyte and embryonic development. Also, it’s controversial whether SLE has an adverse effect on fertility. There is a lack of comprehensive understanding and assessment of fertility in patients with SLE.

Objective

This study was aim to investigate oocyte and embryonic development as well as ovarian reserve, and clinical outcomes in SLE patients during in vitro fertilization (IVF) treatment. By combining data on embryonic and gamete development in SLE patients, we hope to provide new insights into a comprehensive assessment of fertility in SLE patients.

Methods

In this study, we collected data from 34 SLE patients who were previously diagnosed and in remission for a total of 44 IVF cycles and matched 102 infertile women with a total of 148 IVF cycles by Propensity Score Matching (PSM) of 1:3 ratio. We then evaluated baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical outcomes between the two groups.

Results

After PSM matching, baseline characteristics including age, infertility types, and duration, as well as infertility causes overall coincided between the two groups. Anti-müllerian hormone (AMH) was significantly lower in the SLE group vs comparison (1.9 vs. 3.3 ng/mL, P=0.001). The SLE group performed a significant reduction in available embryo rate (76.6% vs. 86.0%, P=0.001), good-quality blastocyst formation rate (35.1% vs. 47.0%, P=0.003), and blastocyst formation rate (51.0% vs. 67.7%, P=0.001) compared to the comparison. As for clinical outcomes, the implantation rate in the SLE group was notably lower (37.9% vs. 54.9%, P=0.022). The CLBR following every embryo-transfer procedure was distinctly lower (41.2% vs 64.7%, P=0.016) in the SLE group vs comparison. Also, the conservative and optimal CLBRs following every complete cycle procedure were significantly reduced in the SLE group vs the comparison (P=0.001, both).

Conclusion

Patients with SLE present worse outcomes in oocyte and embryonic development, thus yielding compromised female fertility and clinical pregnancy. Individualized fertility assessment and early fertility guidance are necessary for these special groups.
Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses
Authors: Jossi Siân E. , Arcuri Melissa , Alshayea Areej , Persaud Ruby R. , Marcial-Juárez Edith , Palmieri Elena , Di Benedetto Roberta , Pérez-Toledo Marisol , Pillaye Jamie , Channell Will M. , Schager Anna E. , Lamerton Rachel E. , Cook Charlotte N. , Goodall Margaret , Haneda Takeshi , Bäumler Andreas J. , Jackson-Jones Lucy H. , Toellner Kai-Michael , MacLennan Calman A. , Henderson Ian R. , Micoli Francesca , Cunningham Adam F.
Published: March 2023

Introduction

Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood.

Methods and results

Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV.

Discussion

Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.
Diabetes mellitus induces a novel inflammatory network involving cancer progression: Insights from bioinformatic analysis and in vitro validation
Authors: Tan Yejun , Kang Jin , Li Hongli , Zhong Aifang , Liu Yaqiong , Zhang Zheyu , Huang Roujie , Cheng Xin , Peng Weijun
Published: March 2023

Background

Patients with diabetes mellitus (DM) have a higher incidence of malignant tumors than people without diabetes, but the underlying molecular mechanisms are still unclear.

Methods

To investigate the link between DM and cancer, we screened publicly available databases for diabetes and cancer-related genes (DCRGs) and constructed a diabetes-based cancer-associated inflammation network (DCIN). We integrated seven DCRGs into the DCIN and analyzed their role in different tumors from various perspectives. We also investigated drug sensitivity and single-cell sequencing data in colon adenocarcinoma as an example. In addition, we performed in vitro experiments to verify the expression of DCRGs and the arachidonic acid metabolic pathway.

Results

Seven identified DCRGs, including PPARG, MMP9, CTNNB1, TNF, TGFB1, PTGS2, and HIF1A, were integrated to construct a DCIN. The bioinformatics analysis showed that the expression of the seven DCRGs in different tumors was significantly different, which had varied effects on diverse perspectives. Single-cell sequencing analyzed in colon cancer showed that the activity of the DCRGs was highest in Macrophage and the lowest in B cells among all cell types in adenoma and carcinoma tissue. In vitro experiments showed that the DCRGs verified by western bolt and PEG2 verified by ELISA were all highly expressed in COAD epithelial cells stimulated by high glucose.

Conclusion

This study, for the first time, constructed a DCIN, which provides novel insights into the underlying mechanism of how DM increases tumor occurrence and development. Although further research is required, our results offer clues for new potential therapeutic strategies to prevent and treat malignant tumors.
Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism
Authors: Zhu Ruizhe , Fang Yilin , Li Hongyu , Liu Ying , Wei Jing , Zhang Shuwei , Wang Liwei , Fan Rui , Wang Lingfang , Li Shengjie , Chen Tingtao
Published: March 2023

Introduction

Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students.

Methods

Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students’ mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism.

Results

The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms.

Conclusion

The results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.
Pattern-recognition receptors in endometriosis: A narrative review
Authors: Guo Bao , Chen Jia hua , Zhang Jun hui , Fang Yuan , Liu Xiao jing , Zhang Jing , Zhu Hai qing , Zhan Lei
Published: March 2023

Endometriosis is closely associated with ectopic focal inflammation and immunosuppressive microenvironment. Multiple types of pattern recognition receptors (PRRs) are present in the innate immune system, which are able to detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in both intracellular and external environments. However, the exact role of PRRs in endometriosis and the underlying molecular mechanism are unclear. PRRs are necessary for the innate immune system to identify and destroy invasive foreign infectious agents. Mammals mainly have two types of microbial recognition systems. The first one consists of the membrane-bound receptors, such as toll-like receptors (TLRs), which recognize extracellular microorganisms and activate intracellular signals to stimulate immune responses. The second one consists of the intracellular PRRs, including nod-like receptors (NLRs) and antiviral proteins retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) with helix enzyme domain. In this review, we mainly focus on the key role of PRRs in the pathological processes associated with endometriosis. PRRs recognize PAMPs and can distinguish pathogenic microorganisms from self, triggering receptor ligand reaction followed by the stimulation of host immune response. Activated immune response promotes the transmission of microbial infection signals to the cells. As endometriosis is characterized by dysregulated inflammation and immune response, PRRs may potentially be involved in the activation of endometriosis-associated inflammation and immune disorders. Toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), nod-like receptor family caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5), nod-like receptor family pyrin domain containing 3 (NLRP3), and c-type lectin receptors (CLRs) play essential roles in endometriosis development by regulating immune and inflammatory responses. Absent in melanoma 2 (AIM2)-like receptors (ALRs) and retinoic acid-inducible gene I-like receptors (RLRs) may be involved in the activation of endometriosis-associated immune and inflammation disorders. PRRs, especially TLRs, may serve as potential therapeutic targets for alleviating pain in endometriosis patients. PRRs and their ligands interact with the innate immune system to enhance inflammation in the stromal cells during endometriosis. Thus, targeting PRRs and their new synthetic ligands may provide new therapeutic options for treating endometriosis.
Add fuel to the fire: Inflammation and immune response in lung cancer combined with COVID-19
Authors: Ai Yanling , Wang Hengyi , Zheng Qiao , Li Songtao , Liu Jingwen , Huang Ju , Tang Jianyuan , Meng Xiangrui
Published: March 2023

The corona virus disease 2019 (COVID-19) global pandemic has had an unprecedented and persistent impact on oncological practice, especially for patients with lung cancer, who are more vulnerable to the virus than the normal population. Indeed, the onset, progression, and prognosis of the two diseases may in some cases influence each other, and inflammation is an important link between them. The original chronic inflammatory environment of lung cancer patients may increase the risk of infection with COVID-19 and exacerbate secondary damage. Meanwhile, the acute inflammation caused by COVID-19 may induce tumour progression or cause immune activation. In this article, from the perspective of the immune microenvironment, the pathophysiological changes in the lungs and whole body of these special patients will be summarised and analysed to explore the possible immunological storm, immunosuppression, and immune escape phenomenon caused by chronic inflammation complicated by acute inflammation. The effects of COVID-19 on immune cells, inflammatory factors, chemokines, and related target proteins in the immune microenvironment of tumours are also discussed, as well as the potential role of the COVID-19 vaccine and immune checkpoint inhibitors in this setting. Finally, we provide recommendations for the treatment of lung cancer combined with COVID-19 in this special group.
Persistence and distribution of dinotefuran in tree of heaven
Authors: Keyzer Justin , Lewis Phillip , McCullough Deborah G.
Published: March 2023

Spotted lanternfly (SLF) (Lycorma delicatula (White)), an invasive planthopper discovered in Pennsylvania, U.S.A. in 2014, feeds for approximately six months by sucking phloem sap from trunks and limbs of tree of heaven, Ailanthus altissima, along with several native trees and woody vines. Basal trunk sprays of dinotefuran, a systemic neonicotinoid insecticide, are commonly used to reduce SLF densities and spread. Information on dinotefuran persistence and within-tree distribution can help identify optimal timing of annual basal trunk sprays, facilitating efficient use of available resources. We applied dinotefuran to 20 uninfested A. altissima trees in early April then periodically sampled foliage to monitor insecticide residues. Foliar dinotefuran residues averaged (± SE) 7.8 ± 1.1 and 6.3 ± 1.2 in July and August, respectively, then dropped significantly to 2.6 ± 0.5 ppm in September. In a second study, 20 A. altissima trees were similarly treated with dinotefuran basal trunk sprays in early June. Trees were felled to collect foliage and phloem from branches and the trunk in either mid-July or September. Foliar residues averaged 12.7 ± 1.3 and 14.6 ± 2.2 ppm in July and September, respectively. For trees felled in July, residues were detected in phloem collected from below the spray line on trunks of seven trees and above the spray line on three trees, averaging 8.6 ± 4.4 and 7.4 ± 2.9 ppm, respectively. In trees felled in September, phloem from below spray lines of seven trees averaged 3.7 ± 1.3 ppm but dinotefuran was not detected in phloem from above the spray line on any trees. Dinotefuran was not detected in phloem sampled from any branches in either July or September. Results suggest dinotefuran basal trunk sprays applied between late May and mid June should persist long enough to effectively control SLF late instars and adults.
Biogenic silica cycling in the Skagerrak
Authors: Spiegel Timo , Dale Andrew W. , Lenz Nina , Schmidt Mark , Sommer Stefan , Kalapurakkal Habeeb Thanveer , Przibilla Anna , Lindhorst Sebastian , Wallmann Klaus
Published: March 2023

Dissolved silicate (H4SiO4) is essential for the formation of the opaline skeletal structures of diatoms and other siliceous plankton. A fraction of particulate biogenic silica (bSi) formed in surface waters sinks to the seabed, where it either dissolves and returns to the water column or is permanently buried. Global silica budgets are still poorly constrained since data on benthic bSi cycling are lacking, especially on continental margins. This study describes benthic bSi cycling in the Skagerrak, a sedimentary depocenter for particles from the North Sea. Biogenic silica burial fluxes, benthic H4SiO4 fluxes to the water column and bSi burial efficiencies are reported for nine stations by evaluating data from in-situ benthic landers and sediment cores with a diagenetic reaction-transport model. The model simulates bSi contents and H4SiO4 concentrations at all sites using a novel power law to describe bSi dissolution kinetics with a small number of adjustable parameters. Our results show that, on average, 1100 mmol m-2 yr-1 of bSi rains down to the Skagerrak basin seafloor, of which 50% is released back to overlying waters, with the remainder being buried. Biogenic silica cycling in the Skagerrak is generally consistent with previously reported global trends, showing higher Si fluxes and burial efficiencies than deep-sea sites and similar values compared to other continental margins. A significant finding of this work is a molar bSi-to-organic carbon burial ratio of 0.22 in Skagerrak sediments, which is distinctively lower compared to other continental margins. We suggest that the continuous dissolution of bSi in suspended sediments transported over long distances from the North Sea leads to the apparent decoupling between bSi and organic carbon in Skagerrak sediments.
Rapid and facile preparation of nanocomposite film heaters for composite manufacturing
Authors: Naseri Iman , Ashrafi Behnam , Jakubinek Michael , Martinez-Rubi Yadienka , Yourdkhani Mostafa
Published: March 2023

Nanocomposite film heaters are promising for out-of-oven (OoO) and energy-efficient curing of fiber-reinforced polymer composites. However, the current techniques for manufacturing nanocomposite film heaters are intensive in terms of time and energy and require expensive resources. In this work, we present a facile and rapid approach for preparation of nanocomposite film heaters with excellent heat generation properties based on a frontally polymerizable resin system. This approach enables rapid fabrication of nanocomposite films within a few minutes and without the need for using expensive equipment, making it suitable for mass production of nanocomposite film heaters. Various characterization techniques are used to determine the morphology, composition, and mechanical properties of nanocomposite films. The electrothermal performance of nanocomposite film heaters are then evaluated under various conditions. Nanostructured heaters exhibit excellent Joule heating properties, where temperatures as high as ∼132°C can be reached within only 2 min using a low input power density of ∼2 W cm−2. Finally, a nanocomposite film heater is used for OoO curing of a small composite panel with minimal energy consumption. Using this approach, 0.1 MJ of energy is consumed during the 4-h cure cycle of a commercial prepreg system, which would otherwise require at least 40.5 MJ of energy to cure using a convection oven.
The integrated stress response is activated in the salivary glands of Sjögren’s syndrome patients
Authors: Carvajal Patricia , Bahamondes Verónica , Jara Daniela , Castro Isabel , Matus Soledad , Aguilera Sergio , Molina Claudio , González Sergio , Hermoso Marcela , Barrera María-José , González María-Julieta
Published: March 2023

Introduction

Primary Sjögren’s syndrome (SS) is an autoimmune exocrinopathy that affects the structure and function of salivary and lachrymal glands. Labial salivary gland (LSG) acinar cells from SS patients lose cellular homeostasis and experience endoplasmic reticulum and oxidative stress. The integrated cellular stress response (ISR) is an adaptive pathway essential for restoring homeostasis against various stress-inducing factors, including pro-inflammatory cytokines, and endoplasmic reticulum and oxidative stress. ISR activation leads eIF2α phosphorylation, which transiently blocks protein synthesis while allowing the ATF4 expression, which induces a gene expression program that seeks to optimize cellular recovery. PKR, HRI, GCN2, and PERK are the four sentinel stress kinases that control eIF2α phosphorylation. Dysregulation and chronic activation of ISR signaling have pathologic consequences associated with inflammation.

Methods

Here, we analyzed the activation of the ISR in LSGs of SS-patients and non-SS sicca controls, determining the mRNA, protein, and phosphorylated-protein levels of key ISR components, as well as the expression of some of ATF4 targets. Moreover, we performed a qualitative characterization of the distribution of ISR components in LSGs from both groups and evaluated if their levels correlate with clinical parameters.

Results

We observed that the four ISR sensors are expressed in LSGs of both groups. However, only PKR and PERK showed increased expression and/or activation in LSGs from SS-patients. eIF2α and p-eIF2α protein levels significantly increased in SS-patients; meanwhile components of the PP1c complex responsible for eIF2α dephosphorylation decreased. ATF4 mRNA levels were decreased in LSGs from SS-patients along with hypermethylation of the ATF4 promoter. Despite low mRNA levels, SS-patients showed increased levels of ATF4 protein and ATF4-target genes involved in the antioxidant response. The acinar cells of SS-patients showed increased staining intensity for PKR, p-PKR, p-PERK, p-eIF2α, ATF4, xCT, CHOP, and NRF2. Autoantibodies, focus score, and ESSDAI were correlated with p-PERK/PERK ratio and ATF4 protein levels.

Discussion

In summary, the results showed an increased ISR activation in LSGs of SS-patients. The increased protein levels of ATF4 and ATF4-target genes involved in the redox homeostasis could be part of a rescue response against the various stressful conditions to which the LSGs of SS-patients are subjected and promote cell survival.