Search

van der Waals (vdW) heterostructures constructed by low-dimensional (0D, 1D, and 2D) materials are emerging as one of the most appealing systems in next-generation flexible photodetection. Currently, hand-stacked vdW-type photodetectors are not compatible with large-area-array fabrication and show unimpressive performance in self-powered mode. Herein, vertical 1D GaN nanorods arrays (NRAs)/2D MoS 2 /PEDOT:PSS in wafer scale have been proposed for self-powered flexible photodetectors arrays firstly. The as-integrated device without external bias under weak UV illumination exhibits a competitive responsivity of 1.47 A W -1 and a high detectivity of 1.2 × 10 11 Jones, as well as a fast response speed of 54/71 µs, thanks to the strong light absorption of GaN NRAs and the efficient photogenerated carrier separation in type-II heterojunction. Notably, the strain-tunable photodetection performances of device have been demonstrated. Impressively, the device at - 0.78% strain and zero bias reveals a significantly enhanced photoresponse with a responsivity of 2.47 A W -1 , a detectivity of 2.6 × 10 11 Jones, and response times of 40/45 µs, which are superior to the state-of-the-art self-powered flexible photodetectors. This work presents a valuable avenue to prepare tunable vdWs heterostructures for self-powered flexible photodetection, which performs well in flexible sensors., (© 2024. The Author(s).)

Objectives: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA., Method: In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12., Results: Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%-95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred., Conclusion: This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found., (© 2024. The Author(s).)

Purpose: This study aimed to investigate Human papillomavirus (HPV) infection and genotyping in men from Chongqing and analyze age-related trends to provide insights for HPV prevention and vaccination plans tailored for men in Chongqing, China., Methods: This study is an observational study. We investigated male patients who underwent HPV screening at two hospitals in Chongqing from 2017 to 2022, totaling 4,381 cases, aged 18 to 85. HPV genotyping was conducted using the Hybribio Rapid GenoArray kit., Results: Among the 4,381 men, the overall HPV prevalence was 14.9%, peaking at 19.3% in 2022. Single HPV infection was 11.5%, and multiple infection was 3.4%. The most prevalent genotypes were HPV-52, HPV-16, and HPV-58. Single high-risk HPV infection peaked in the 36-45 age group, while multiple high-risk HPV infection decreased with age (P-trend < 0.01). Prevalence in the ≤ 25 age group was 3.7%. Single low-risk HPV infection also decreased with age (P-trend = 0.03). Genotypes covered by the nonavalent vaccine had the highest prevalence, increasing with age. Co-infection of HPV-16 with HPV-52 and HPV-58 was common. Single HPV infections were prevalent in cases of urethritis (30.8%), anogenital warts (36.4%), and genital warts (26.3%), while multiple HPV infections were significant in anogenital warts (18.2%)., Conclusions: Single HPV infection was predominant in Chongqing, with HPV-52, HPV-16, HPV-58, HPV-53, and HPV-39 being the most prevalent genotypes. The prevalence of genotypes covered by the nonavalent vaccine increased with age. This study offers valuable insights for developing male-specific HPV prevention strategies in Chongqing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aims to investigate the feasibility and value of modular splenic hilar lymphadenectomy (MSHL) in LTG for advanced PGC located at the greater curvature., Study Design: A retrospective-controlled research included 54 patients diagnosed with advanced PGC located at the greater curvature who underwent LTG combined with spleen-preserving hilar lymphadenectomy between January 2020 and December 2022 at the same treatment center. A total of 20 patients underwent classic splenic hilar lymphadenectomy (CSHL) using a medial approach (classic group), while 34 patients underwent MSHL (modular group). We summarized the technical points, caveats, and critical steps of the MSHL technique and observed and compared clinical indexes between the two groups., Results: All operations were successful without conversion to laparotomy. The mean operation time, mean splenic hilar lymph node dissection (LND) time, median intraoperative blood loss, and blood loss from splenic hilar LND were all significantly lower in the modular group than in the classic group (p < 0.05). The amount of NO.10 lymph nodes (LNs) was significantly higher in the modular group than in the classic group (p < 0.05). In the classic group, one patient experienced intraoperative splenic vein injury, and one experienced spleen laceration, whereas no intraoperative complications occurred in the modular group. The median postoperative feeding time, exhaust time, defecation time, and postoperative stay were all significantly lower in the modular group compared to the classic group (p < 0.05). In the modular group, one patient experienced Clavien-Dindo I complication and one Clavien-Dindo II complication, while in the classic group, one patient experienced Clavien-Dindo II complication and one Clavien-Dindo IIIa complication. There were no patient was re-hospitalized within 30 days after surgery., Conclusion: The modular splenic hilar LND technique can simplify complicated surgical procedures in SPSHL and reduce the risk of intraoperative bleeding and collateral damage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c., Methods: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c., Results: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels., Conclusions: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care., Registration Number: ClinicalTrials.gov Identifier: NCT03610984., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from Angelica dahurica, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25 mg/kg twice weekly for 6 weeks), and found that both IMP (25 mg/kg and 12.5 mg/kg) and dexrazoxane 12.5 mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25 µg/mL relieved DOX (1 μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disorder; however, the understanding of the pathogenesis of PCOS remains unclear. Necroptosis is a newly discovered mechanism of cell death, and it is closely related to reproductive endocrine-related diseases. This study aimed to investigate the hub necroptosis-related genes in PCOS patients and its correlation with immune cell infiltration by bioinformatics methods., Method: The gene expression chip result matrix and the annotation matrix files of the GSE34526, GSE8157, and GSE5090 datasets were downloaded from the GEO database. We analyzed the expression and correlation of the necroptosis-related genes in all samples, constructed a diagnostic model based on all necroptosis-related genes and genes with significant differences, performed unsupervised clustering of samples and gene enrichment analysis, and evaluated the correlations between the hub gene and immune cell infiltration levels by the R packages GSVA and CIBERSORT. Finally, PPI networks were constructed using the Cytoscape software GeneMANIA plug-in, and the miRNA, transcription factors, RBP, and drugs were predicted., Conclusion: Necroptosis-related genes have important relationships in the development of PCOS and are potentially associated with immune infiltration in PCOS patients., (© 2024. The Author(s).)

Objective: Splenic flexure mobilization (SFM) is a major challenge in laparoscopic left hemicolectomy. This study aims to assess the safety and effectiveness of the pancreas-guided SFM technique during laparoscopic left hemicolectomy., Methods: From January 2018 to December 2023, 352 patients with left-sided colon cancer underwent laparoscopic left hemicolectomy. Based on the SFM method used, the patients were divided into the pancreas-guided group (167 cases) or the "Three Approaches Roundabout"/classic group (185 cases). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups., Results: The two groups had no significant differences in baseline indicators (P > 0.05). All surgeries were successful without needing to convert to laparotomy, and there were no combined organ resections involving the spleen or pancreas in either group. The mean duration of surgery was significantly lower in the pancreas-guided group than in the classic group (P < 0.01). The median volume of intraoperative blood loss in the pancreas-guided group was lower than that in the classic group (P < 0.01). Through video playback, it was found that the retro-pancreatic space had been entered during operation in 8 cases (4.3%) in the classic group, while there were no such occurrences in the pancreas-guided group. This difference was statistically significant (P < 0.05). The difference in the number of lymph nodes cleared, postoperative hospital stays, and incidence of complications were not statistically significant (all P > 0.05) between the groups., Conclusion: The pancreas-guided SFM technique is a safe and feasible option for laparoscopic left hemicolectomy. Our study's findings suggest that this approach facilitates accurate access to the correct anatomic plane, potentially improving surgical efficiency., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Despite chimeric antigen receptor (CAR) T-cell therapy has achieved great advances in recent year, approximately 50% of relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL) patients treated with CAR-T experience relapse 6 months post CAR-T treatment. CD20 express on 30 to 50% of B-ALL, which makes CD20 Monoclonal Antibody as one of the potential therapy strategies to decrease the tumor burden and improve the efficacy of CAR-T therapy. Adding Rituximab to chemotherapy protocol had been demonstrated to improve the outcome for CD20-positive ALL. However, rare study explored the influence of Rituximab combined with CAR-T therapy., Methods: We retrospectively analyzed 20 r/r B-ALL patients who received CAR-T therapy, all of whom had failed multiple lines of therapy. Before CAR-T infusion, we administered Rituximab to 10 patients with high CD20 expression at a dose of 375 mg/m 2 for 1 day. Meanwhile, we selected 10 patients with the comparable features who underwent CAR-T treatment without Rituximab in the same period as the control group. In vitro, the surface molecule expression and killing of CAR-T post Rituximab-treated B-ALL cells co-incubated with CAR-T cells were detected by flow cytometry., Results: The median follow-up of Rituximab and Control groups were 29.27 and 9.83 months. We found that adding Rituximab may confer a favorable prognosis compared with Control group. The 2-year overall survival (OS) and leukemia-free survival (LFS) rates both were longer in the Rituximab group (90% vs. 26.7%, p = 0.0342; 41.7% vs. 25%, p = 0.308). In vitro, we observed that Rituximab-treated tumour cells are more sensitive to CAR-T killing and a broad range of cytokines and chemokines were produced when Rituximab-treated Nalm-6 cells co-cultured with 19-22CAR-T cells, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). To investigate whether Rituximab has an effect on CAR-T persistence, we stimulated CAR-T cells repeatedly in vitro with Rituximab-treated Nalm-6 to evaluate the changes in CAR-T surface exhaustion molecules at different times. We found that the expression of exhaustion molecules (LAG-3, PD-1, TIM-3) on CAR-T cells were significantly lower in the Rituximab group than in the Control group., Conclusion: Rituximab combined with CAR-T therapy is effective for improving the long-term prognosis of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improves CAR-T efficacy by sensitizing ALL to CART-mediated cytotoxicity and reducing CAR-T exhaustion., (© 2024. The Author(s).)

Although previous studies have investigated the relationship between inhibition of return (IOR) and multisensory integration, the influence of non-spatial has not been explored. The present study aimed to investigate the influence of non-spatial IOR on audiovisual integration by using a "prime-neutral cue-target" paradigm. In Experiment 1, which manipulated prime validity and target modality, the targets were positioned centrally, revealing significant non-spatial IOR effects in the visual, auditory, and audiovisual modalities. Analysis of relative multisensory response enhancement (rMRE) indicated substantial audiovisual integration enhancement in both valid and invalid target conditions. Furthermore, the enhancement was weaker for valid targets than for invalid targets. In Experiment 2, the targets were positioned above and below to rule out repetition blindness (RB); this experiment successfully replicated the results observed in Experiment 1. Notably, Experiments 1 and 2 consistently found that the correlation between modality differences and rMRE for valid targets indicated that differences in signal strength between visual and auditory modalities contributed to a reduction in audiovisual integration. However, the absence of correlation with the invalid target suggests that attention, as a key factor, may play a significant role in this process. The present study highlights how non-spatial IOR reduces audiovisual integration and sheds light on the complex interaction between attention and multisensory integration., (© 2023. The Psychonomic Society, Inc.)

Blautia wexlerae (B. wexlerae) is a strong candidate with the potential to become a next-generation probiotics (NGPs) and has recently been shown for the first time to exhibit potential in modulating host metabolic levels and alleviating metabolic diseases. However, the factors affecting the change in abundance of B. wexlerae and the pattern of its abundance change in the associated indications remain to be further investigated. Here, we summarize information from published studies related to B. wexlerae; analyze the effects of food source factors such as prebiotics, probiotics, low protein foods, polyphenols, vitamins, and other factors on the abundance of B. wexlerae; and explore the patterns of changes in the abundance of B. wexlerae in metabolic diseases, neurological diseases, and other diseases. At the same time, the development potential of B. wexlerae was evaluated in the direction of functional foods and special medical foods., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Targeting the heat shock protein-90 (Hsp90) chaperone machinery in various cancers with 200 monotherapy or combined-therapy clinical trials since 1999 has not yielded any success of food and drug administration approval. Blames for the failures were unanimously directed at the Hsp90 inhibitors or tumors or both. However, analyses of recent cellular and genetic studies together with the Hsp90 data from the Human Protein Atlas database suggest that the vast variations in Hsp90 expression among different organs in patients might have been the actual cause. It is evident now that Hsp90β is the root of dose-limiting toxicity (DLT), whereas Hsp90α is a buffer of penetrated Hsp90 inhibitors. The more Hsp90α, the safer Hsp90β, and the lower DLT are for the host. Unfortunately, the dramatic variations of Hsp90, from total absence in the eye, muscle, pancreas, and heart to abundance in reproduction organs, lung, liver, and gastrointestinal track, would cause the selection of any fair toxicity biomarker and an effective maximum tolerable dose (MTD) of Hsp90 inhibitor extremely challenging. In theory, a safe MTD for the organs with high Hsp90 could harm the organs with low Hsp90. In reverse, a safe MTD for organs with low or undetectable Hsp90 would have little impact on the tumors, whose cells exhibit average 3-7% Hsp90 over the average 2-3% Hsp90 in normal cells. Moreover, not all tumor cell lines tested follow the "inhibitor binding-client protein degradation" paradigm. It is likely why the oral Hsp90 inhibitor TAS-116 (Pimitespib), which bypasses blood circulation and other organs, showed some beneficiary efficacy by conveniently hitting tumors along the gastrointestinal track. The critical question is what the next step will be for the Hsp90 chaperone as a cancer therapeutic target., Competing Interests: Declarations of interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests. Wei Li reports financial support was provided by the National Institutes of Health. Mei Chen reports financial support was provided by the National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although gemcitabine (GEM) is the first‑line drug for advanced pancreatic adenocarcinoma (PAAD), the development of GEM resistance severely limits the effectiveness of this chemotherapy. This study investigated the mechanisms of ecotropic viral integration site 2 A (EVI2A) for resistance to GEM and immune evasion in PAAD. GEM resistance-related biomarkers were predicted using GEO datasets, and GEM-resistant PAAD cells were generated. EVI2A was found expressed highly in GEM-resistant PAAD cells. Gain-of-function analyses revealed that EVI2A encouraged the proliferation and motility of GEM-resistant cells and prevented apoptosis. In addition, EVI2A reduced T cell effector activation. SMYD2 was overexpressed in GEM-resistant cells, and SMYD2 enhanced H3K36me2 modification of EVI2A, thereby promoting EVI2A expression. SMYD2 reduced the sensitivity of GEM-resistant cells, which was reversed by EVI2A knockdown. SMYD2 increased the amount of M2 macrophages (co-cultured with PAAD cells) and decreased T cell effector activation (co-cultured with macrophage supernatant), and the number of M2 macrophages was decreased and T cell effectors were activated following EVI2A knockdown. Our findings indicate that EVI2A, manipulated by the SMYD2-H3K36me2 epigenetic axis, promoted GEM resistance and M2 macrophage-mediated immune evasion in PAAD. Therefore, EVI2A might represent a therapeutic target for overcoming GEM resistance and immunosuppressive environment in PAAD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibroblastic tumor, characterized to be an aggressive disease with high frequency of ALK rearrangement, rapid recurrence, and poor prognosis. Primary EIMS of thoracic origin is rarely observed. Herein, we described a case of 28-year-old female developed primary EIMS in the anterior mediastinum with hepatic metastasis. The EIMS displayed sheet-like growth of epithelioid and spindle cells with enlarged nuclei, abundant and eosinophilic cytoplasm, and infiltration of inflammatory cells. Immunohistochemical staining revealed positive expression of ALK in the nuclear membrane, and ALK rearrangement was identified by polymerase chain reaction assay. Alectinib showed partial response, and achieved a meaningful survival benefit for four months. Based on this case report and literature review, ALK inhibitor reveals promising activity on the rare but aggressive EIMS. Awareness of EIMS in thoracic disease and its clinicopathological features is essential to avoid erroneous diagnosis., (© 2024. The Author(s).)

Background: Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children., Objective: We conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies., Methods: A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected., Results: Fifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals., Conclusions: The XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Live micro-ecological agents, such as probiotics, have demonstrated a significant role in the preservation of human health, encompassing oral health maintenance and regulation of oral microbiota. Here, a total of 20 patients diagnosed with chronic periodontitis were recruited and randomly assigned into two cohorts based on completion of physiotherapy: a placebo group (n = 10) and a probiotic group (n = 10). The actual efficacy was assessed by administering chewable tablets (5 × 10 9  CFU/tablet) containing the probiotics Lactobacillus salivarius LS97, Lactobacillus paracasei LC86, and Lactobacillus acidophilus LA85 to patients with chronic periodontitis. For the placebo group, chewable tablets without probiotics were administered, while maintaining consistency with the rest of the ingredients used in the probiotic group. Saliva and plaque samples were collected at different time points (0, 1, and 3 months) and subjected to 16S amplicon sequencing for microbial structure analysis. Salivary IgA content was determined using enzyme immunoassay, whereas clinical chronic periodontal pocket depth (PD) and bleeding on probe index (BOP +) were employed to evaluate the actual efficacy of probiotic-assisted physiological intervention in chronic periodontitis treatment. Compared to the placebo group, the probiotic intervention resulted in a significant increase in salivary IgA levels among patients, accompanied by a notable decrease in PD and BOP + levels. Furthermore, the probiotic intervention led to a substantial reduction in Fusobacterium and Porphyromonas counts, while significantly increasing Lactobacillus abundance within the dental plaque microbiota of patients. Importantly, no significant alterations were observed in the overall structure of both salivary and dental plaque microbiota following the probiotic intervention. The administration of this live probiotic agent consistently and significantly enhances the oral immune response in patients with chronic periodontitis, thereby augmenting the effectiveness of physical interventions for this condition. Moreover, it effectively reduces the abundance of pathogenic microbes associated with chronic periodontitis without causing substantial alterations to the salivary and dental plaque microbiota composition. Trial registration: Chinese Clinical Trial Registry (ChiCTR) ( https://www.chictr.org.cn ) under the registration number ChiCTR2300074108., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cervical cancer poses a significant health burden for women globally, and the rapid proliferation of cervical cancer cells greatly worsens patient prognosis. Long non-coding RNAs (lncRNAs) play a crucial role in regulating tumor cell proliferation. However, the involvement of lncRNAs in cervical cancer cell proliferation remains unclear. In this study, we investigated the lncRNA SIX1-1, which was found to be upregulated in cervical cancer tissues and cell lines. Functional assays revealed that knockdown of SIX1-1 inhibited cell proliferation in vitro and reduced tumor growth in vivo. Mechanistically, SIX1-1 was predominantly localized in the nucleus and could bind with DNMT1 protein. The expression of SIX1-1 enhanced the interaction of DNMT1 with RASD1 promoter, leading to the methylation of the promoter and decreased mRNA transcription. Then RASD1 downregulation activated the cAMP/PKA/CREB signaling pathway, promoting cell proliferation. Rescue experiments showed that knockdown of RASD1 restored the inhibited cell proliferation caused by decreased expression of SIX1-1, indicating that RASD1 acted as the functional mediator of SIX1-1. In conclusion, SIX1-1 promoted cervical cancer cell proliferation by modulating RASD1 expression. This suggests that targeting the SIX1-1/RASD1 axis could be a potential antitumor strategy for cervical cancer., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Gastric cancer (GC) is highly heterogeneous and prone to metastasis, which are obstacles to the effectiveness of treatment. The basement membrane (BM) acts as a barrier to tumor cell invasion and metastasis. It is critical to investigate the relationship between BM status, metastasis, and patient prognosis. In several large cohorts, we investigated BM gene expression-based molecular classification and risk-prognosis models for GC, examined tumor microenvironment (TME) differences among different molecular subtypes, and developed risk models in predicting prognosis, immunotherapy effectiveness, and chemotherapy resistance. Three GC subtypes (BMclusterA/B/C) based on BM gene expression status were discovered. Each of the three GC subtypes has unique immune infiltration and activated oncogenic signals. Moreover, a 6-gene score (BMscore) predictive model was developed. The low BMscore group had a high tumor mutation burden, high immunogenicity, and low RHOJ expression levels, implying that individuals with GC in this category may be more susceptible to immunotherapy and treatment. The EMT subtype showed a considerably higher BMscore than the other subtypes in the Asian Organization for Research on Cancer (ACRG) molecular classification. Endothelial cells, smooth muscle cells, and fibroblasts may be engaged in regulating BM reorganization in GC progression, according to single-cell transcriptome analyses. In conclusion, we defined a novel molecular classification of GC based on BM genes, developed a prognostic risk model, and elucidated the cell subpopulations involved in BM remodeling at the single-cell level. This study has deepened the understanding of the relationship between GC metastasis and BM alterations, achieved prognostic stratification, and guided therapy., (© 2024. The Author(s).)

Ovarian aging reduced the quality of oocytes, resulting in age-related female infertility. It is reported that mesenchymal stem cells (MSCs) therapy can improve age-related ovarian function decline and the success rate of in vitro maturation (IVM) in assisted reproductive therapy. In order to investigate the effectiveness and mechanisms of MSCs to enhance oocyte quality of cumulus oocyte complexes (COCs) in advanced age, this study focus on the respective functional improvement of oocytes and granulosa cells (GCs) from aging mice and further to explore and verify the possible mechanisms. Here, we studied a popular but significant protein of follicular development, Forkhead box O-3a (FOXO3a), which is a transcription factor that mediates a variety of cellular processes, but the functions of which in regulating oocyte quality in MSCs therapy still remain inconclusive. In this study, the RNA-seq data of metaphase II (MII) oocytes and GCs isolated from COCs confirmed that, GCs of immature follicles show the most potential to be the targeted cells of bone marrow mesenchymal stem cells (BMSCs) by FOXO3a signaling pathway. Furthermore, we demonstrated the effectiveness of BMSCs co-culture with aging COCs to enhance oocyte quality and found its mechanism to function via ameliorating the biological function of GCs by alleviating FOXO3a levels. These results provide significant fundamental research on MSCs therapy on ovarian aging, as well as offering guidance for raising the success rate of assisted reproductive technology such IVM in clinical and non-clinical settings., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Key Message: Multiple regulatory pathways of Zostera japonica to salt stress were identified through growth, physiological, transcriptomic and metabolomic analyses. Seagrasses are marine higher submerged plants that evolved from terrestrial monocotyledons and have fully adapted to the high saline seawater environment during the long evolutionary process. As one of the seagrasses growing in the intertidal zone, Zostera japonica not only has the ability to quickly adapt to short-term salt stress but can also survive at salinities ranging from the lower salinity of the Yellow River estuary to the higher salinity of the bay, making it a good natural model for studying the mechanism underlying the adaptation of plants to salt stress. In this work, we screened the growth, physiological, metabolomic, and transcriptomic changes of Z. japonica after a 5-day exposure to different salinities. We found that high salinity treatment impeded the growth of Z. japonica, hindered its photosynthesis, and elicited oxidative damage, while Z. japonica increased antioxidant enzyme activity. At the transcriptomic level, hypersaline stress greatly reduced the expression levels of photosynthesis-related genes while increasing the expression of genes associated with flavonoid biosynthesis. Meanwhile, the expression of candidate genes involved in ion transport and cell wall remodeling was dramatically changed under hypersaline stress. Moreover, transcription factors signaling pathways such as mitogen-activated protein kinase (MAPK) were also significantly influenced by salt stress. At the metabolomic level, Z. japonica displayed an accumulation of osmolytes and TCA mediators under hypersaline stress. In conclusion, our results revealed a complex regulatory mechanism in Z. japonica under salt stress, and the findings will provide important guidance for improving salt resistance in crops., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Unlike human epidermal growth factor receptor 2 (HER2) amplification or exon 20 insertions, missense mutations in the extracellular domain (ECD), transmembrane domain (TMD), and intracellular domain (ICD) of the HER2 protein have been implicated as oncogenic in non-small cell lung cancer (NSCLC). However, their molecular subtypes, structural disparities, and clinical responses to current medical treatments, particularly HER2-targeted tyrosine kinase inhibitors (TKIs), remain unclear in NSCLC and warrant investigation., Methods: A real-world observational ATLAS study was conducted to gather and analyze therapeutic outcomes of chemotherapy or TKIs for heterogeneous HER2 missense mutations in NSCLC. Computational models of typical ECD, TMD, and ICD mutations were utilized to explore their structural variances., Results: We screened 37 eligible patients with HER2-activating missense mutations, of which 35 patients who had received chemotherapy or HER2-targeted TKIs as first-line therapy were available for response assessment. The median progression-free survival (PFS) for chemotherapy was 4.43 months (95% confidence interval [CI], 3.77-5.10), with an objective response rate (ORR) of 26.1% (6/23) and a disease control rate (DCR) of 17/23 (73.9%). The administration of afatinib, dacomitinib, and pyrotinib, HER2-targeted TKIs, achieved a median PFS of 4.65 months, with an ORR of 33.3% (4/12) and a DCR of 83.3% (10/12). Molecular modeling and computational simulations of ECD, TMD, and ICD mutations revealed their distinct structural characteristics., Conclusion: In comparison to chemotherapy, HER2-targeted TKIs demonstrated similar activity and PFS benefits for HER2-activating missense mutations in NSCLC., (© 2024. The Author(s).)

Context: Silicon carbide nanowires (SiCNWs) are considered a promising alternative material for application in lithium-ion batteries, with researchers striving to develop new electrode materials that exhibit high capacity and high charge/discharge rate performance. To gain a deeper understanding of the application of SiCNWs in semiconductor material science and energy supply fields, we investigated the effects of nanoscale and surface lithiation on the electrical and mechanical properties of SiCNWs grown along the [111] direction. First-principles calculation was used to study their geometries, electronic structures, and associated electrochemical properties. Herein, we considered SiCNWs with full hydrogen passivation, full lithium passivation, and mixed passivation at different sizes. The formation energy indicates that the stability of SiCNWs increases with the increasing diameter, and the surface-lithiated SiC nanowires (Li-SiCNWs) are found to be energetically stable. The mixed passivated SiCNWs exhibit the properties of indirect band gap with the increase of lithium atoms on the surface, while the fully lithium passivated nanowires exhibit metallic behavior. Charge analysis shows that a portion of the electrons on the lithium atoms are transferred to the surface atoms of the nanowires and electrons prefer to cluster more near the C atoms. Additionally, Li-SiCNWs still have good mechanical resistance during the lithiation process. The stable open-circuit voltage range and theoretical capacity of these SiCNWs indicate their suitability as anode materials., Method: In this study, Materials Studio 8.0 was used to construct the models of the SiCNWs. And all the density functional theory (DFT) calculations were performed by the Vienna ab initio Simulation Package (VASP). The self-consistent field calculations are performed over a Monkhorst-Pack net of 1 × 1 × 6 k-points. The energy convergence criteria for the self-consistent field calculation were set to 10 -5  eV/atom with a cutoff energy of 400 eV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The effective combination of semen cryopreservation and artificial insemination has a positive effect on the conservation of germplasm resources, production and breeding, etc. However, during the process of semen cryopreservation, the sperm cells are very susceptible to different degrees of physical, chemical, and oxidative stress damage. Oxidative damage is the most important factor that reduces semen quality, which is affected by factors such as dilution equilibrium, change of osmotic pressure, cold shock, and enzyme action during the freezing-thawing process, which results in the aggregation of a large amount of reactive oxygen species (ROS) in sperm cells and affects the quality of semen after thawing. Therefore, the method of adding antioxidants to semen cryoprotective diluent is usually used to improve the effect of semen cryopreservation. The aim of this experiment was to investigate the effects of adding five antioxidants (GLP, Mito Q, NAC, SLS, and SDS) to semen cryoprotection diluent on the cryopreservation effect of semen from Saanen dairy goats. The optimal preservation concentrations were screened by detecting sperm viability, plasma membrane integrity, antioxidant capacity, and acrosomal enzyme activities after thawing, and the experimental results were as follows: the optimal concentrations of GLP, Mito Q, NAC, SLS, and SDS added to semen cryopreservation diluent at different concentrations were 0.8 mg/mL, 150 nmol/L, 0.6 mg/mL, 0.15 mg/ mL, 0.6 mg/mL, and 0.15 mg/mL. The optimal concentrations of the five antioxidants were added to the diluent and analyzed after 1 week of cryopreservation, and it was found that sperm viability, plasma membrane integrity, and mitochondrial activity were significantly enhanced after thawing compared with the control group (P < 0.05), and their antioxidant capacity was significantly enhanced (P < 0.05). Therefore, the addition of the above five antioxidants to goat sperm cryodilution solution had a better enhancement of sperm cryopreservation. This study provides a useful reference for exploring the improvement of goat semen cryoprotection effect., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The research on bio-based flocculants for waste resource utilization and environmental protection has garnered significant attention. Bio-based flocculants encompass plant-based, animal-based, and microbial variants that are prepared and modified through biological, chemical, and physical methods. These flocculants possess abundant functional groups, unique structures, and distinctive characteristics. This review comprehensively discussed the removal rates of conventional pollutants and emerging pollutants by bio-based flocculants, the interaction between these flocculants and pollutants, their impact on flocculation performance in wastewater treatment, as well as their application cost. Furthermore, it described the common challenges faced by bio-based flocculants in practical applications along with various improvement strategies to address them. With their safety profile, environmental friendliness, efficiency, renewability, and wide availability from diverse sources, bio-based flocculants hold great potential for widespread use in wastewater treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To develop and validate a predictive combined model for metastasis in patients with clear cell renal cell carcinoma (ccRCC) by integrating multimodal data., Materials and Methods: In this retrospective study, the clinical and imaging data (CT and ultrasound) of patients with ccRCC confirmed by pathology from three tertiary hospitals in different regions were collected from January 2013 to January 2023. We developed three models, including a clinical model, a radiomics model, and a combined model. The performance of the model was determined based on its discriminative power and clinical utility. The evaluation indicators included area under the receiver operating characteristic curve (AUC) value, accuracy, sensitivity, specificity, negative predictive value, positive predictive value and decision curve analysis (DCA) curve., Results: A total of 251 patients were evaluated. Patients (n = 166) from Shandong University Qilu Hospital (Jinan) were divided into the training cohort, of which 50 patients developed metastases; patients (n = 37) from Shandong University Qilu Hospital (Qingdao) were used as internal testing, of which 15 patients developed metastases; patients (n = 48) from Changzhou Second People's Hospital were used as external testing, of which 13 patients developed metastases. In the training set, the combined model showed the highest performance (AUC, 0.924) in predicting lymph node metastasis (LNM), while the clinical and radiomics models both had AUCs of 0.845 and 0.870, respectively. In the internal testing, the combined model had the highest performance (AUC, 0.877) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.726 and 0.836, respectively. In the external testing, the combined model had the highest performance (AUC, 0.849) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.708 and 0.804, respectively. The DCA curve showed that the combined model had a significant prediction probability in predicting the risk of LNM in ccRCC patients compared with the clinical model or the radiomics model., Conclusion: The combined model was superior to the clinical and radiomics models in predicting LNM in ccRCC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Intraoperative reconstruction of endoscopic scenes is a key technology for surgical navigation systems. The accuracy and efficiency of 3D reconstruction directly determine the effectiveness of navigation systems in a variety of clinical applications. While current deformable SLAM algorithms can meet real-time requirements, their underlying reliance on regular templates still makes it challenging to efficiently capture abrupt geometric features within scenes, such as organ contours and surgical margins., Methods: We propose a novel real-time monocular deformable SLAM algorithm with geometrically adapted template. To ensure real-time performance, the proposed algorithm consists of two threads: a deformation mapping thread updates the template at keyframe rate and a deformation tracking thread estimates the camera pose and the deformation at frame rate. To capture geometric features more efficiently, the algorithm first detects salient edge features using a pre-trained contour detection network and then constructs the template through a triangulation method with guidance of the salient features., Results: We thoroughly evaluated this method on Mandala and Hamlyn datasets in terms of accuracy and performance. The results demonstrated that the proposed method achieves better accuracy with 0.75-7.95% improvement and achieves consistent effectiveness in data association compared with the closest method., Conclusion: This study verified an adaptive template does improve the performance of reconstruction of dynamic laparoscopic Scenes with abrupt geometric features. However, further exploration is needed for applications in laparoscopic surgery with incisal margins caused by surgical instruments. This research serves as a crucial step toward enhanced automatic computer-assisted navigation in laparoscopic surgery. Code is available at https://github.com/Tang257/SLAM-with-geometrically-adapted-template ., (© 2024. CARS.)

Key Message: Calcium polypeptide plays a key role during cadmium stress responses in rice, which is involved in increasing peroxidase activity, modulating pectin methylesterase activity, and regulating cell wall by reducing malondialdehyde content. Cadmium (Cd) contamination threatens agriculture and human health globally, emphasizing the need for sustainable methods to reduce cadmium toxicity in crops. Calcium polypeptide (CaP) is a highly water-soluble small molecular peptide acknowledged for its potential as an organic fertilizer in promoting plant growth. However, it is still unknown whether CaP has effects on mitigating Cd toxicity. Here, we investigated the effect of CaP application on the ability to tolerate toxic Cd in rice. We evaluated the impact of CaP on rice seedlings under varying Cd stress conditions and investigated the effect mechanism of CaP mitigating Cd toxicity by Fourier transform infrared spectroscopy (FTIR), fluorescent probe dye, immunofluorescent labeling, and biochemical analysis. We found a notable alleviation of Cd toxicity by reduced malondialdehyde content and increased peroxidase activity. In addition, our findings reveal that CaP induces structural alterations in the root cell wall by modulating pectin methylesterase activity. Altogether, our results confirm that CaP not only promoted biomass accumulation but also reduced Cd concentration in rice. This study contributes valuable insights to sustainable strategies for addressing Cd contamination in agricultural ecosystems., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transdermal drug delivery systems (TDDS) have drawbacks such as poor absorption, low blood concentration, and delayed effects. Dissolving microneedle has sharp tips and short length, which overcome patients' pain and improve transdermal efficiency but has low mechanical strength and drug loading capacity. This study thereby proposes a microemulsion-encapsulated and long-time-released transdermal microneedle (MN) delivery system with estradiol (Es) as the model drug. The microemulsion (ME) was optimized by utilizing the pseudo-ternary phase diagram and D-optimal mixture design. The estradiol microemulsion-encapsulated microneedle (Es-ME-MN) was optimized by Box-Behnken design and prepared by freeze-thaw method. The Es-ME-MN obtained was characterized and evaluated through a large variety of studies. Es-ME-MN had sufficient mechanical strength to pierce skin and was safe enough, the length of which was 600 μm, and the Es content was 177.12 ± 0.72 μg/patch without drug-excipient chemical interaction. In vitro permeation study showed that Es-ME-MN has a higher transdermal efficiency and lower retention capacity than commercial estradiol patch and conventional MN. Es plasma concentration began to increase at 3 h and remained at 12.98-23.52 ng/mL until 72 h by pharmacokinetic experiments in the Es-ME-MN group. Es-ME-MN rapidly achieves effective blood concentrations through needle puncture and microemulsion delivery and maintains blood concentrations through the baseplate long-time release. Microemulsion-encapsulated, organic solvent-free, and long-time-released transdermal microneedle will make progress and provide a new idea for transdermal delivery of lipophilic drugs., (© 2023. Controlled Release Society.)

Purpose: Olaparib, an inhibitor of poly-(adenosine diphosphate-ribose) polymerase (PARP), has been shown to have anticancer benefits in patients with pancreatic cancer who have a germline mutation in BRCA1/2. However, resistance acquired on long-term exposure to olaparib significantly impedes clinical efficacy., Methods: In this study, the chromatin accessibility and differentially expressed transcripts of parental and olaparib-resistant pancreatic cancer cell lines were assessed using the Assay for Transposase Accessible Chromatin with sequencing (ATAC-seq) and mRNA-seq. Detection of downstream genes regulated by transcription factors using ChIP (Chromatin immunoprecipitation assay)., Results: According to pathway enrichment analysis, differentially expressed genes in olaparib-resistant cells were remarkably enriched in the NF-κB signaling pathway. With ATAC-seq, we identified chromatin regions with higher accessibility in olaparib-resistant cells and predicted a series of important transcription factors. Among them, activating transcription factor 3 (ATF3) was significantly highly expressed. Functional experiments verified that inhibition of ATF3 suppressed the NF-κB pathway significantly and restored olaparib sensitivity in olaparib-resistant cells., Conclusion: Experiments in vitro and in vivo indicate ATF3 enhances olaparib resistance through the NF-κB signaling pathway, suggesting that ATF3 could be employed as an olaparib sensitivity and prognostic indicator in patients with pancreatic cancer., (© 2023. Springer Nature Switzerland AG.)

The infection of Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of economic losses in sericulture. Thus, it is essential to establish rapid and effective method for BmNPV detection. In the present study, we have developed a recombinase-aided amplification (RAA) to amplify the BmNPV genomic DNA at 37 °C within 30 min, and achieved a rapid detection method by coupling with a lateral flow dipstick (LFD). The RAA-LFD method had a satisfactory detection limit of 6 copies/μL of recombinant plasmid pMD19-T-IE1, and BmNPV infection of silkworm can be detected 12 h post-infection. This method was highly specific for BmNPV, and without cross-reactivity to other silkworm pathogens. In contrast to conventional polymerase chain reaction (PCR), the RAA-LFD assay showed higher sensitivity, cost-saving, and especially is apt to on-site detection of BmNPV infection in the sericulture production., (© 2023. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Non-coding RNA appears to be involved in wound repair. Competing endogenous RNA (ceRNA) appears to be an important post-transcriptional mechanism, it means that long noncoding RNA (lncRNA) or circular RNA (circRNA) acts as a microRNA (miRNA) sponge to further regulate mRNA. However, ceRNA network related to wound repair after prostatectomy has yet been constructed. TULP is the main surgical method of prostatectomy, but there have been no reports of TULP rat models in the past. We simulated TULP on rats, and observed the whole process of wound injury and repair after operation through pathological examination of wound tissue. Next, we discovered 732 differentially expressed lncRNAs (DElncRNAs), 47 differentially expressed circRNAs (DEcircRNAs), 17 differentially expressed miRNAs (DEmiRNAs), and 1892 differentially expressed mRNAs (DEmRNAs) related to wound repair after TULP through full transcriptome microarray and bioinformatics methods, and confirmed the reliability of transcriptome data by quantitative Reverse Transcription PCR (qRT-PCR), and immunohistochemistry. Then, we constructed the lncRNA- and circRNA-associated ceRNA regulatory networks related to wound repair after TULP in rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that molecules in these networks were mainly involved in inflammatory infiltration, cell differentiation, and intercellular interactions and involved signal pathways such as the PI3K-Akt signaling pathway. Thus, this study successfully established the TULP model in rats, revealed potentially important biomarkers and ceRNA networks after prostatectomy in rats, and provided theoretical support for the repair of post-prostatectomy wound., (© 2023. The Author(s).)

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igβ respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The investigation about association between vitamin D level and clinical outcomes of assisted reproductive treatment showed various outcomes. This study aimed to review the correlation between vitamin D and outcomes of assisted reproductive treatment. The search was registered on the PROSPERO database (CRD42023458040). PubMed, Embase, Medline, ClinicalTrials.gov, and Cochrane databases were searched up to July 2023. Twenty-three observational studies were selected for meta-analysis. Comparing groups with deficient and 'insufficient + sufficient' vitamin D level, meta-analysis showed positive correlation between clinical pregnancy rate and vitamin D (OR 0.81, 95%CI: 0.70, 0.95, P = 0.0001). Comparing groups with 'deficient + insufficient' and sufficient vitamin D level, meta-analysis showed positive correlation between vitamin D and clinical pregnancy rate (OR 0.71, 95%CI: 0.55, 0.91, P = 0.006), vitamin D and live birth rate (OR 0.69, 95%CI: 0.54, 0.89, P = 0.003). Subgroup analysis did not show the source of high heterogeneity. No correlation was found in biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. In dose-response meta-analysis, a nonlinear association was found between vitamin D levels and outcomes when levels are below approximately 24 ng/L. The study shows that vitamin D level is associated with clinical pregnancy rate and live birth rate. Low vitamin D level does not influence biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. Furthermore, 24 ng/L may be a possible threshold of vitamin D concentration in assisted reproduction therapy., (© 2024. The Author(s).)

Skin-attachable electronics have garnered considerable research attention in health monitoring and artificial intelligence domains, whereas susceptibility to electromagnetic interference (EMI), heat accumulation issues, and ultraviolet (UV)-induced aging problems pose significant constraints on their potential applications. Here, an ultra-elastic, highly breathable, and thermal-comfortable epidermal sensor with exceptional UV-EMI shielding performance and remarkable thermal conductivity is developed for high-fidelity monitoring of multiple human electrophysiological signals. Via filling the elastomeric microfibers with thermally conductive boron nitride nanoparticles and bridging the insulating fiber interfaces by plating Ag nanoparticles (NPs), an interwoven thermal conducting fiber network (0.72 W m -1  K -1 ) is constructed benefiting from the seamless thermal interfaces, facilitating unimpeded heat dissipation for comfort skin wearing. More excitingly, the elastomeric fiber substrates simultaneously achieve outstanding UV protection (UPF = 143.1) and EMI shielding (SE T  > 65, X-band) capabilities owing to the high electrical conductivity and surface plasmon resonance of Ag NPs. Furthermore, an electronic textile prepared by printing liquid metal on the UV-EMI shielding and thermally conductive nonwoven textile is finally utilized as an advanced epidermal sensor, which succeeds in monitoring different electrophysiological signals under vigorous electromagnetic interference. This research paves the way for developing protective and environmentally adaptive epidermal electronics for next-generation health regulation., (© 2024. The Author(s).)

Purposes: STAT1 is a transduction and transcriptional regulator that functions within the classical JAK/STAT pathway. In addition to chronic mucocutaneous candidiasis, bacterial infections are a common occurrence in patients with STAT1 gain-of-function (GOF) mutations. These patients often exhibit skewing of B cell subsets; however, the impact of STAT1-GOF mutations on B cell-mediated humoral immunity remains largely unexplored. It is also unclear whether these patients with IgG within normal range require regular intravenous immunoglobulin (IVIG) therapy., Methods: Eleven patients (harboring nine different STAT1-GOF mutations) were enrolled. Reporter assays and immunoblot analyses were performed to confirm STAT1 mutations. Flow cytometry, deep sequencing, ELISA, and ELISpot were conducted to assess the impact of STAT1-GOF on humoral immunity., Results: All patients exhibited increased levels of phospho-STAT1 and total STAT1 protein, with two patients carrying novel mutations. In vitro assays showed that these two novel mutations were GOF mutations. Three patients with normal total IgG levels received regular IVIG infusions, resulting in effective control of bacterial infections. Four cases showed impaired affinity and specificity of pertussis toxin-specific antibodies, accompanied by reduced generation of class-switched memory B cells. Patients also had a disrupted immunoglobulin heavy chain (IGH) repertoire, coupled with a marked reduction in the somatic hypermutation frequency of switched Ig transcripts., Conclusion: STAT1-GOF mutations disrupt B cell compartments and skew IGH characteristics, resulting in impaired affinity and antigen-specificity of antibodies and recurrent bacterial infections. Regular IVIG therapy can control these infections in patients, even those with normal total IgG levels., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: BrBCAT1 encoding a branched-chain amino acid aminotransferase was responsible for the glossy trait, which was verified by allelic mutants in Chinese cabbage. The glossy characteristic, thanks to the epicuticular wax crystal deficiency, is an excellent commodity character for leafy vegetables. Herein, two allelic glossy green mutants, wdm11 and wdm12, were isolated from an ethyl methane sulfonate (EMS)-mutagenized population of Chinese cabbage, and the mutant phenotype was recessive inherited. Cryo-SEM detected that epicuticular wax crystal in the mutant leaves was virtually absent. MutMap and Kompetitive allele-specific PCR analyses demonstrated that BraA06g006950.3C (BrBCAT1), homologous to AtBCAT1, encoding a branched-chain amino acid aminotransferase was the candidate gene. A SNP (G to A) on the fourth exon of BrBCAT1 in wdm11 caused the 233rd amino acid to change from glycine (G) to aspartic acid (D). A SNP (G to A) on the second exon of BrBCAT1 in wdm12 led to the 112th amino acid change from glycine (G) to arginine (R). Both of the allelic mutants had genetic structural variation in the candidate gene, which indicated that the mutant phenotype was triggered by the BrBCAT1 mutation. The expression levels of BrBCAT1 and genes related to fatty acid chain extension were decreased significantly in the mutant compared to the wild-type, which might result in epicuticular wax crystal deficiency in the mutants. Our findings proved that the mutation of BrBCAT1 induced the glossy phenotype and provided a valuable gene resource for commodity character improvement in Chinese cabbage., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fertilization can change the composition of antibiotic resistance genes(ARGs) and their host bacteria in agricultural fields, while complex microbial activities help ARGs into crops and transmit them to humans through agricultural products.Therefore, this study constructed a farmland food chain with soil-lettuce-snail as a typical structure, added genetically engineered Pseudomonas fluorescens containing multidrug-resistant plasmid RP4 to track its spread in the farmland food chain, and used different fertilization methods to explore its influence on the spread and diffusion of ARGs and intl1 in the farmland food chain. It was found that exogenous Pseudomonas can enter plants from soil and pass into snails' intestines, and there is horizontal gene transfer phenomenon of RP4 plasmid in bacteria. At different interfaces of the constructed food chain, the addition of exogenous drug-resistant bacteria had different effects on the total abundance of ARGs and intl1. Fertilization, especially manure, not only promoted the spread of Pseudomonas aeruginosa and the transfer of RP4 plasmid levels, but also significantly increased the total abundance of ARGs and intl1 at all interfaces of the constructed food chain. The main ARGs host bacteria in the constructed food chain include Proteobacteria, Bacteroides, and Firmicutes, while Flavobacterium of Bacteroides is the unique potential host bacteria of RP4 plasmid. In conclusion, this study provides a reference for the risk assessment of ARGs transmitted to the human body through the food chain, and has important practical significance to reduce the antibiotic resistance contamination of agricultural products and ensure the safety of vegetable basket., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study proposed a noninvasive, automated, in vivo assessment method based on optical coherence tomography (OCT) and deep learning techniques to qualitatively and quantitatively analyze the biological effects of 2-µm laser-induced skin damage at different irradiation doses. Different doses of 2-µm laser irradiation established a mouse skin damage model, after which the skin-damaged tissues were imaged non-invasively in vivo using OCT. The acquired images were preprocessed to construct the dataset required for deep learning. The deep learning models used were U-Net, DeepLabV3+, PSP-Net, and HR-Net, and the trained models were used to segment the damage images and further quantify the damage volume of mouse skin under different irradiation doses. The comparison of the qualitative and quantitative results of the four network models showed that HR-Net had the best performance, the highest agreement between the segmentation results and real values, and the smallest error in the quantitative assessment of the damage volume. Based on HR-Net to segment the damage image and quantify the damage volume, the irradiation doses 5.41, 9.55, 13.05, 20.85, 32.71, 52.92, 76.71, and 97.24 J/cm² corresponded to a damage volume of 4.58, 12.56, 16.74, 20.88, 24.52, 30.75, 34.13, and 37.32 mm³. The damage volume increased in a radiation dose-dependent manner., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Early and accurate diagnosis of osteosarcomas (OS) is of great clinical significance, and machine learning (ML) based methods are increasingly adopted. However, current ML-based methods for osteosarcoma diagnosis consider only X-ray images, usually fail to generalize to new cases, and lack explainability. In this paper, we seek to explore the capability of deep learning models in diagnosing primary OS, with higher accuracy, explainability, and generality. Concretely, we analyze the added value of integrating the biochemical data, i.e., alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and design a model that incorporates the numerical features of ALP and LDH and the visual features of X-ray imaging through a late fusion approach in the feature space. We evaluate this model on real-world clinic data with 848 patients aged from 4 to 81. The experimental results reveal the effectiveness of incorporating ALP and LDH simultaneously in a late fusion approach, with the accuracy of the considered 2608 cases increased to 97.17%, compared to 94.35% in the baseline. Grad-CAM visualizations consistent with orthopedic specialists further justified the model's explainability., Competing Interests: Conflict of interestThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Spatial simulation and projection of ecosystem services value (ESV) changes caused by urban growth are important for sustainable development in arid regions. We developed a new model of cellular automata based grasshopper optimization algorithm (named GOA-CA) for simulating urban growth patterns and assessing the impacts of urban growth on ESV changes under climate change scenarios. The results show that GOA-CA yielded overall accuracy exceeding 98%, and FOM for 2010 and 2020 were 43.2% and 38.1%, respectively, indicating the effectiveness of the model. The prairie lost the highest economic ESVs (192 million USD) and the coniferous yielded the largest economic ESV increase (292 million USD) during 2000-2020. Using climate change scenarios as urban future land use demands, we projected three scenarios of the urban growth of Urumqi for 2050 and their impacts on ESV. Our model can be easily applied to simulating urban development, analyzing its impact on ESV and projecting future scenarios in global arid regions., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Metaplastic breast carcinoma (MBC), a category of breast cancer, includes different histological types, which are occasionally mixed and heterogeneous. Considering the heterogeneity of cancer cells in a tumour mass has become highly significant, not only from a biological aspect but also for clinical management of recurrence. This study aimed to analyse the immunohistochemical and molecular profiles of each MBC component of a tumour mass. Twenty-five MBC tumours were histologically evaluated, and the most frequent MBC component (c) was squamous cell carcinoma (SCC), followed by spindle cell carcinoma (SpCC). A total of 69 components of MBC and non-MBC in formalin-fixed paraffin-embedded sections were examined for 7 markers by immunohistochemistry. SCC(c) were significantly PTEN negative and CK14 positive, and SpCC(c) were significantly E-cadherin negative and vimentin positive. Multivariate analyses revealed that immunohistochemical profiles of normal/intraductal (IC)(c), no special type (NST)(c), and MBC(c) differed; moreover, SCC(c) and SpCC(c) were distinctly grouped. PTEN gene mutation was detected only in SCC(c) (2/7), but not in SpCC(c). Next-generation sequence analyses for 2 cases with tumours containing SCC(c) demonstrated that PTEN gene mutation increased progressively from IC(c) to NST(c) to SCC(c). In conclusion, the immunohistochemical and molecular profiles of the SCC(c) of MBC are distinct from those of the SpCC(c)., (© 2024. The Author(s).)

Herein, novel catalysts of Fe-containing zeolite-A (Fe/zeolite-A) were synthesized by exchanging iron ions into zeolite-A framework, and short-chain organic acids (SCOAs) were employed as chelating agents. Reactive Brilliant Blue KN-R (KN-R) was used as a model pollutant to evaluate the performance of these catalysts based on the heterogeneous Fenton reaction. The results showed that Fe-OA/3A, which applied zeolite-3A as the supporter and oxalic as the chelating agent, presented the most prominent KN-R decolorization efficiency. Under the initial pH of 2.5, 0.4 mM KN-R could be totally decolorized within 20 min. However, the mineralization efficiency of KN-R was only 58.2%. Therefore, anthraquinone dyes were introduced to modify zeolite-3A. As a result, the mineralization efficiency of KN-R was elevated to 92.7% when using Alizarin Violet (AV) as the modifier. Moreover, the modified catalysts exhibited excellent stability, the KN-R decolorization efficiency could be maintained above 95.0% within 20 min after operating for nine cycles. The mechanism revealed that the Fe(II)/Fe(III) cycle was accelerated by AV-modified catalyst thus prompting the KN-R decolorization in Fenton-like system. These findings provide new insights for preparing catalysts with excellent activity and stability for dye wastewater treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There is a lack of clinical data to support the effectiveness and safety of postbiotics in the modulation of human oral microbiota and oral health care. Here, volunteers were recruited and randomly assigned to two cohorts: a placebo group (n = 15) and a postbiotic group (n = 16). The placebo group used toothpaste that did not contain postbiotics, while the postbiotic group used toothpaste with postbiotics (3 × 10 10  CFU inactivated Lactobacillus salivarius LS97, L. paracasei LC86, and L. acidophilus LA85). Saliva samples were collected at different time points and the immunoglobulin A (IgA) and short-chain fatty acid (SCFA) levels were determined, while the salivary microbiota was analyzed by 16S rRNA amplicon sequencing. The results showed that salivary IgA levels and acetic and propionic acid levels were notably higher in the postbiotic group (P < 0.05), accompanied by an increase in the level of alpha diversity of the salivary microbiota, and these indexes remained high 1 month after discontinuing the use of toothpaste with or without postbiotics. A notable decrease in the relative abundance of the unclassified&#95;Enterobacteriaceae, Klebsiella, Escherichia, etc. in the postbiotic group was accompanied by a notable increase in Ruminofilibacter and Lactobacillus. However, both groups did not cause significant changes in the overall structure of the host salivary microbiota. In conclusion, postbiotics dramatically and consistently improved oral immunity levels and SCFA content in the host. In addition, postbiotics were able to increase the level of microbial alpha diversity and down-regulate the abundance of some harmful microbes without significantly altering the structure of the host salivary microbiota. Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ) under the registration number ChiCTR2300074088., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD., (© 2024. The Author(s).)

Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10 -8 ). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: We aimed to determine the prevalence of cardiovascular involvement in our Blau syndrome (BS) cohort and provide detailed analysis of their cardiovascular manifestations and outcome. We also tried to find out the risk factors for developing cardiovascular involvement., Methods: Clinical manifestations, laboratory findings, and treatments were reviewed. Clinical features were compared between children with cardiovascular involvement and those without angiocardiopathy., Results: A total of 38 BS children were eligible for final analysis. Among them, 13 (34.2%) developed Takayasu-like vasculitis and/or cardiopathy. Compared with those without angiocardiopathy, recurrent fever was more frequent in BS patients with cardiovascular involvement (p < 0.001). What is more, tumor necrosis factor alpha antagonists (anti-TNF) were more urgently needed in children with cardiovascular involvement (p = 0.015). BS patients with cardiovascular involvement include 4 with Takayasu-like vasculitis and 9 with cardiopathy. The onset of cardiovascular manifestations ranged from 0.75 to 18.5 years of age, with most cases occurring before school period. Symptoms were elusive and lacked specificity, such as dizziness, short of breath, and edema. Some patients were even identified because of the unexpected hypertension during follow-up. Cardiopathy and vasculitis occurred in patients with different genotypes. Imaging changes were discovered before the presentation of the typical triad in 3/4 patients with Takayasu-like vasculitis. Three children developed left ventricular dysfunction with decreased left ventricular ejection fraction. Combination of glucocorticoids and methotrexate with anti-TNF agents is a common treatment option for these BS patients. In the cohort, BS-related cardiovascular involvement was controlled well, with cardiac structural and functional abnormalities completely recovered and slower progression of vasculitis lesions., Conclusion: Cardiovascular manifestations is not rare in BS patients. Because of its insidious onset, a systematic and comprehensive assessment of cardiovascular involvement should be performed in newly diagnosed patients with BS. Aggressive initiation of anti-TNF agents may be beneficial to improve the prognosis. Key Points • About 34.2% patients with Blau syndrome developed Takayasu-like vasculitis and/or cardiopathy. • Compared with those without angiocardiopathy, recurrent fever and application of anti-TNF agents were more frequent in BS patients with cardiovascular involvement (p < 0.001, p = 0.015) • Regular assessment of cardiovascular involvement is extremely necessary because of its insidious onset., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Sleeping in an unfamiliar environment, such as a sleep laboratory, is thought to disturb sleep in healthy individuals and could express a hyperarousal state called the first night effect. Insomnia disorder (ID) is a highly prevalent health problem characterized by increased arousal during the night and daytime. Whether or not a similar phenomenon occurs in patients with ID is unclear. This study aimed to investigate the effect of an unfamiliar environment on the sleep of patients with ID., Methods: In an unfamiliar sleep laboratory, polysomnographic recording testing was performed for two consecutive nights in patients with ID and age- and sex-matched healthy control subjects (HC). We collected sleep diaries and questionnaires regarding sleep, medical conditions, psychological status, and health history. Sleep continuity and architecture in both groups were compared and analyzed for two consecutive nights., Results: Participants with ID (n = 39)  and HC (n = 35) demonstrated differentially poor sleep on laboratory adaptation after exposure to the sleep laboratory. Patients with ID had longer rapid eye movement (REM) latency on the first night than on the second sleep night. HC showed increased duration and percentage of N1, decreased duration and percentage of N3, and decreased REM percentage during initial nights compared to subsequent nights. The other sleep variables showed no differences between the first and second sleep nights in patients with ID and HC., Conclusions: An unfamiliar sleep environment does not aggravate the disruption of sleep continuity and sleep architecture but only affects the REM latency in patients with ID compared with HC., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)