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Abstract Background Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients’ limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients’ physical function and the burden of caregivers. Methods/design A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training. Discussion Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden. Trial registration Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.

Pichia pastoris, a methylotrophic yeast, can utilize methanol as a carbon source and energy source to synthesize high-value chemicals, and is an ideal host for biomanufacturing. Constructing the P. pastoris cell factory is somewhat impeded due to the absence of genetic tools for manipulating multi-gene biosynthetic pathways. To broaden its application in the field of metabolic engineering, this study identified and screened 15 novel integration sites in P. pastoris using CRISPR-Cpf1 genome editing technology, with EGFP serving the reporter protein. These integration sites have integration efficiencies of 10–100 % and varying expression strengths, which allow for selection based on the expression levels of genes as needed. Additionally, these integrated sites are applied in the heterologous biosynthesis of P. pastoris, such as the astaxanthin biosynthetic pathway and the carbon dioxide fixation pathway of the Calvin-Benson-Bassham (CBB) cycle. During the three-site integration process, the 8 genes of the CBB cycle were integrated into the genome of P. pastoris. This indicates the potential of these integration sites for integrating large fragments and suggests their successful application in metabolic engineering of P. pastoris. This may lead to improved efficiency of genetic engineering in P. pastoris.

Abstract Objective To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU). Methods This retrospective cohort study was conducted at a large children’s hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission. Results A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN. Conclusion This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes.

Abstract Objective The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of β-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. Methods From our initial sample of 52 patients, we observed 48 patients with β-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. Results The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with βCD41-42/βCD17 and 6 cases with βCD41-42/β-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P

Abstract The construction of an ecologically livable rural environment requires treating rural domestic waste. Farmers, as key participants in rural domestic waste disposal, can improve the rural environment by disposing of domestic waste in an environmentally friendly manner. Few studies have examined the cadre–farmer relationship and its impact on rural waste pollution. Using a questionnaire survey of farmers in Shaanxi Province, China, this study estimates the effect of cadre–farmer relationship on their willingness to treat domestic waste. The findings indicate that a positive cadre–farmer relationship significantly increases farmers’ willingness to treat domestic waste. This positive relationship can also strengthen the positive effects of institutional rules on waste treatment willingness. Further mechanism analysis shows that a good cadre–farmer relationship mobilizes farmers to protect the environment and to comply with national ecological laws and regulations, enhancing their willingness to treat domestic waste. These findings enrich research on rural domestic waste management.

Abstract Background The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. Methods we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. Findings We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. Interpretation The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Abstract Background YouTube, a widely recognized global video platform, is inaccessible in China, whereas Bilibili and TikTok are popular platforms for long and short videos, respectively. There are many videos related to laryngeal carcinoma on these platforms. This study aims to identify upload sources, contents, and feature information of these videos on YouTube, Bilibili, and TikTok, and further evaluate the video quality. Methods On January 1, 2024, we searched the top 100 videos by default sort order (300 videos in total) with the terms “laryngeal carcinoma” and “throat cancer” on YouTube, “喉癌” on Bilibili and TikTok. Videos were screened for relevance and similarity. Video characteristics were documented, and quality was assessed by using the Patient Education Materials Assessment Tool (PEMAT), Video Information and Quality Index (VIQI), Global Quality Score (GQS), and modified DISCERN (mDISCERN). Results The analysis included 99 YouTube videos, 76 from Bilibili, and 73 from TikTok. Median video lengths were 193 s (YouTube), 136 s (Bilibili), and 42 s (TikTok). TikTok videos demonstrated higher audience interaction. Bilibili had the lowest ratio of original contents (69.7%). Treatment was the most popular topic on YouTube and Bilibili, while that was the prognosis on TikTok. Solo narration was the most common video style across all platforms. Video uploaders were predominantly non-profit organizations (YouTube), self-media (Bilibili), and doctors (TikTok), with TikTok authors having the highest certification rate (83.3%). Video quality, assessed using PEMAT, VIQI, GQS, and mDISCERN, varied across platforms, with YouTube generally showing the highest scores. Videos from professional authors performed better than videos from non-professionals based on the GQS and mDISCERN scores. Spearman correlation analysis showed no strong relationships between the video quality and the audience interaction. Conclusions Videos on social media platforms can help the public learn about the knowledge of laryngeal cancer to some extent. TikTok achieves the best flow, but videos on YouTube are of the best quality. However, the video quality across all platforms still needs enhancement. We need more professional uploaders to ameliorate the video quality related to laryngeal carcinoma. Content creators also should be aware of the certification, the originality, and the style of video shooting. As for the platforms, refining the algorithm will allow users to receive more high-quality videos.

Abstract CRISPR-based gene therapy offers precise targeting and specific editing of disease-related gene sequences, potentially yielding long-lasting treatment effects. However, efficient delivery remains a significant challenge for its widespread application. In this study, we design a novel short peptide-conjugated bioreducible polymer named TSPscp as a safe and effective delivery vector for the CRISPR system. Our results show that TSPscp markedly boosts transcriptional activation and genome editing activities of multiple CRISPR systems as confirmed by decomposition-seq and Deep-seq, which is resulted from its capability in facilitating delivery of plasmid DNA by promoting cellular uptake and lysosomal escape. Additionally, TSPscp further enhances genome editing of CRISPR by delivery of minicircle DNA, a condensed form of regular plasmid DNA. More importantly, TSPscp significantly improves delivery and genome editing of CRISPR system in vivo. In summary, our study highlights TSPscp as a promising delivery tool for CRISPR applications in vivo. Graphical Abstract

Abstract Purpose This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions. Methods Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort. Results Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value. Conclusions This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.

Abstract Background C-X-C motif chemokine ligand 1 (CXCL1) and epithelial growth factor (EGF) are highly secreted by oral squamous cell carcinoma (OSCC) cells and tumor-associated macrophages, respectively. Recent studies have shown that there is intricate "cross-talk" between OSCC cells and macrophages. However, the underlying mechanisms are still poorly elucidated. Methods The expression of CXCL1 was detected by immunohistochemistry in OSCC clinical samples. CXCL1 levels were evaluated by RT‒PCR and ELISA in an OSCC cell line and a normal epithelial cell line. The expression of EGF was determined by RT‒PCR and ELISA. The effect of EGF on the proliferation of OSCC cells was evaluated by CCK-8 and colony formation assays. The effect of EGF on the migration and invasion ability and epithelial-mesenchymal transition (EMT) of OSCC cells was determined by wound healing, Transwell, RT‒PCR, Western blot and immunofluorescence assays. The polarization of macrophages was evaluated by RT‒PCR and flow cytometry. Western blotting was used to study the molecular mechanism in OSCC. Results The expression of C-X-C motif chemokine ligand 1 (CXCL1) was higher in the OSCC cell line (Cal27) than in immortalized human keratinocytes (Hacat cells). CXCL1 derived from Cal27 cells upregulates the expression of epithelial growth factor (EGF) in macrophages. Paracrine stimulation mediated by EGF further facilitates the epithelial-mesenchymal transition (EMT) of Cal27 cells and initiates the upregulation of CXCL1 in a positive feedback-manner. Mechanistically, EGF signaling-induced OSCC cell invasion and migration can be ascribed to the activation of NF-κB signaling mediated by the epithelial growth factor receptor (EGFR), as determined by western blotting. Conclusions OSCC cell-derived CXCL1 can stimulate the M2 polarization of macrophages and the secretion of EGF. Moreover, EGF significantly activates NF-κB signaling and promotes the migration and invasion of OSCC cells in a paracrine manner. A positive feedback loop between OSCC cells and macrophages was formed, contributing to the promotion of OSCC progression.

IntroductionAcquired vulvar lymphangioma (AVL), a rare disease caused by the dilation of superficial lymphatic vessels secondary to deep lymphatic vessel injury, is characterized by a wide range of morphological diversity and massive exudate. This morphological heterogeneity has often led to misdiagnosis or non-diagnosis. The management of AVL presents a therapeutic challenge due to the absence of a standardized treatment protocol.Case presentationA 53-year-old female patient, previously received surgical treatments for stage IIb cervical squamous cell carcinoma, presented with vulvar enlargement and copious amount of yellow exudate seven years post-treatment. Clinically, the patient exhibited chronic vulvar swelling, with easily-exudated nodules. The vulvar biopsy revealed lymphatic vessel dilation with lymphocyte infiltration, consistent with AVL. Due to the extensive lesions and severe exudate, staged excisions of bilateral vulvar lesions were performed at one-month intervals. Follow-up examinations of this patient for one-year post-surgery showed no evidence of recurrence.ConclusionIn this instance, AVL manifest secondary to cervical cancer surgery, as a result of damage to the deep lymphatic vessels of the vulva, with characteristic symptoms of copious amounts of exudate and vulvar lesions with diverse morphologies, which provides a cautionary note for physicians. Besides, the staged resection strategy in this case may offer insights into surgical treatment protocol for extensive AVL.

Introduction and Objectives: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. Patients and Methods: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017–2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999–2016) to assess the correlation with mortality. Results: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. Conclusions: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

Summary: Resident memory T cells (TRMs) play a vital role in regional immune defense. Although laboratory rodents have been extensively used to study fundamental TRM biology, poor isolation efficiency and low cell survival rates have limited the implementation of TRM-focused high-throughput assays. Here, we engineer a murine vaginal epithelial organoid (VEO)-CD8 T cell co-culture system that supports CD8 TRM differentiation. These in-vitro-generated TRMs are phenotypically and transcriptionally similar to in vivo TRMs. Pharmacological and genetic approaches showed that transforming growth factor β (TGF-β) signaling plays a crucial role in their differentiation. The VEOs in our model are susceptible to viral infections and the CD8 T cells are amenable to genetic manipulation, both of which will allow a detailed interrogation of antiviral CD8 T cell biology. Altogether we have established a robust in vitro TRM differentiation system that is scalable and can be subjected to high-throughput assays that will rapidly add to our understanding of TRMs.

Background: Retroperitoneal leiomyomas are rare benign smooth muscle tumours. Diagnosing these tumours is often challenging due to their unique growth site and nonspecific clinical manifestations. There are a few reports of leiomyomas with intratumoral bleeding. Case presentation: A patient with a giant retroperitoneal leiomyoma presented with multiple-organ dysfunction syndrome accompanied by a progressive decrease in haemoglobin. Computed tomography (CT) revealed two cystic tumours in the abdominal cavity. The patient was underwent transabdominal retroperitoneal tumour resection. During surgery, we found two retroperitoneal tumours—one contained approximately 9000 mL of dark red fluid and the other contained 1000 mL of light brown fluid. She has recovered well without any complications. Conclusions: There have been only a few reports of retroperitoneal leiomyomas with intratumoral bleeding. This case highlights the importance of recognizing intratumoral haemorrhage in patients with large leiomyomas and a progressive decrease in haemoglobin after ruling out external haemorrhage. If necessary, dynamic monitoring via CT may help clarify the diagnosis.

This research delves into the correlation between offline bullying and online unethical behavior among college students; and examines the potential mediating influences of anger rumination and perceived relative deprivation. The findings suggest that anger rumination, perceived relative deprivation, offline bullying, and online unethical behavior exhibit significant positive correlations with each other. Offline bullying is a strong predictor of online unethical behavior among college students, with the dual mediating effects of perceived relative deprivation and anger rumination on the relationship between offline bullying and online unethical behavior. This suggests that offline bullying directly influences college students' online unethical behavior and also influences it indirectly through anger rumination and perceived relative deprivation.

Congenital microtia is the most common cause of auricular defects, with a prevalence of approximately 5.18 per 10,000 individuals. Autologous rib cartilage grafting is the leading treatment modality at this stage of auricular reconstruction currently. However, harvesting rib cartilage may lead to donor site injuries, such as pneumothorax, postoperative pain, chest wall scarring, and deformity. Therefore, in the pursuit of better graft materials, biomaterial scaffolds with great histocompatibility, precise control of morphology, non-invasiveness properties are gradually becoming a new research hotspot in auricular reconstruction. This review collectively presents the exploit and application of 3D printing biomaterial scaffold in auricular reconstruction. Although the tissue-engineered ear still faces challenges before it can be widely applied to patients in clinical settings, and its long-term effects have yet to be evaluated, we aim to provide guidance for future research directions in 3D printing biomaterial scaffold for auricular reconstruction. This will ultimately benefit the translational and clinical application of cartilage tissue engineering and biomaterials in the treatment of auricular defects.

Background: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. Methods: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. Results: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P

Abstract Background Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing). Results By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases. Conclusions Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.

Abstract Manipulating surface charge, electric field, and plasma afterglow in a non-equilibrium plasma is critical to control plasma-surface interaction for plasma catalysis and manufacturing. Here, we show enhancements of surface charge, electric field during breakdown, and afterglow by ferroelectric barrier discharge. The results show that the ferroelectrics manifest spontaneous electric polarization to increase the surface charge by two orders of magnitude compared to discharge with an alumina barrier. Time-resolved in-situ electric field measurements reveal that the fast polarization of ferroelectrics enhances the electric field during the breakdown in streamer discharge and doubles the electric field compared to the dielectric barrier discharge. Moreover, due to the existence of surface charge, the ferroelectric electrode extends the afterglow time and makes discharge sustained longer when alternating the external electric field polarity. The present results show that ferroelectric barrier discharge offers a promising technique to tune plasma properties for efficient plasma catalysis and electrified manufacturing.

Abstract Background Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. Case description We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. Conclusions The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.

Abstract The global environmental issue of soil contamination with antibiotic-resistance genes has garnered increased attention in recent years due to its impact on ecosystems and human health. Despite this recognition, researchers face challenges in comprehensively understanding the mechanisms underlying the production and dissemination of soil resistance genes, particularly in relation to their implications for human health. This lack of understanding poses a barrier to the development of effective and precise control strategies. Biochar, a sustainable material, exhibits favorable adsorption properties characterized by its large pores and specific surface area. Therefore, we propose to explore the potential application of biochar addition in soil resistance gene management. In order to establish a solid research foundation in this area, in this paper we review the mechanisms underlying the generation and accumulation of soil resistance genes over the last decade, along with their transmission pathways and interfacial interactions. Biochar may help repair soil resistance genes by affecting factors like antibiotic levels, environmental conditions, enzymatic activity, and gene migration mechanisms, opening up new research possibilities. Graphical Abstract

Epidemiology of carbapenem-resistant organisms (CRO) has focused on transmission in acute care hospital or long-term care facility (LTCF) settings. Few investigations have examined community-associated (CA)-CRO, with no consensus about common exposures. To explore possible exposures, the New York City (NYC) Department of Health and Mental Hygiene investigated suspected CA-CRO cases through routine surveillance among NYC residents with specimens collected during December 2020-May 2023. CA-CRO cases were defined as urine or skin specimens with bacterial cultures exhibiting carbapenem resistance, among individuals aged ≤70 years with no international travel, hospitalization, or LTCF stays within 12 months before specimen collection. Inclusion was determined by reviewing data from health information exchanges, when available electronic medical records, and telephone screening for those not excluded through record review. We identified 426 suspected cases for review, those not meeting the case definition were excluded; 44 individuals were not reached for screening. A preliminary questionnaire was fielded with 12 individuals and then refined to capture additional potential exposures. Analyses were completed with 23 individuals interviewed with the refined questionnaire. Of the 23, 70% were female; 39% were Hispanic, 17% Black, and 17% White; their median age was 60 years (range: 26-70 years). Further, 83% reported an outpatient appointment, 48% reported an outpatient procedure/surgery, and 9% reported having a hospitalized household member, all within 12 months before specimen collection; 26% had a urinary catheter or indwelling device within 2 days of specimen collection. Additionally, 30% reported taking antibiotics within 3 months of specimen collection, 52% denied taking antibiotics, 9% were unsure about antibiotic use, and 9% did not answer the question. Whole genome sequencing (WGS) was performed on 14 available isolates from CA-CRO cases by the NYC Public Health Laboratory or Wadsworth Center (WC), of which only 7 could be compared with isolates previously sequenced at WC (2017-2023). Six isolates were separated by >50 mutation events, suggesting no close genomic relationship. One isolate from 2021 was 11 mutation events from a 2018 isolate from the same individual, consistent with the expected evolutionary rate. While infrequent, CA-CRO cases occur in NYC. Outpatient healthcare, antibiotic use, and urinary catheters or indwelling devices were common self-reported exposures. Analyses were limited by screening non-response. Increased specimen availability for WGS could enhance investigation of CA-CRO exposure patterns. Health information exchange data were often incomplete and future surveillance could benefit from healthcare and public health partnerships and better documentation for more complete electronic medical histories.

BackgroundMitochondrial damage contributes to apoptosis, oxidative stress, and inflammation, which collectively impact the immune system’s function and the tumor microenvironment (TME). These processes, in turn, influence tumor cell growth, migration, and response to treatment.ObjectiveWe conducted a bibliometric analysis to elucidate the complex interactions between mitochondrial damage, the immune system, and the TME.MethodsData were sourced from the Science Citation Index Core Collection (WoSCC) and analyzed using advanced tools like VOSviewer and Citespace. Our focus was on literature published between 1999 and 2023 concerning the interactions between mitochondrial damage and the TME, as well as immune responses to tumors. The analysis included regional contributions, journal influence, institutional collaborations, authorship, co-cited authors, and keyword citation bursts.ResultsOur research encompassed 2,039 publications, revealing an increasing trend in annual output exploring the relationship between mitochondrial damage, TME dynamics, and immune responses. China, the United States, and South Korea emerged as the leading contributors. Prominent institutions included Institut National de la Santé et de la Recherche Médicale, University of Texas System, China Medical University, and Sun Yat-sen University. Key journals in this field are the International Journal of Molecular Sciences, Mitochondrion, and the European Journal of Pharmacology. Liang H and Wallace DC were identified as the most productive and co-cited authors, respectively. Keyword analysis highlighted the critical roles of inflammatory responses, oxidative stress, and the immune system in recent research.ConclusionThis bibliometric analysis provides a comprehensive overview of historical and current research trends, underscoring the pivotal role of mitochondrial damage in the TME and immune system.

BackgroundNon-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS).MethodsA post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion.ResultsAfter adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03–2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01–1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66–4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01–1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes.ConclusionsNAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

An intramolecular isotopic study was conducted on natural gases collected from coal-derived gas reservoirs in sedimentary basins of China to determine their position-specific isotope distributions. The propane from the Turpan-Hami Basin exhibited negative ΔC-T (δ13Ccentral-δ13Cterminal) values ranging from −3.9‰ to −0.3‰, with an average of −2.1‰. Propane from the Ordos Basin, Sichuan Basin, and Tarim Basin showed positive ΔC-T values, with averages of 1.3‰, 5.4‰ and 7.6‰, respectively. Position-specific carbon isotope compositions reveal the precursors and the propane generation pathways in the petroliferous basins. Propane formed from the thermal cracking of Type III kerogen has larger δ13Ccentral and δ13Cterminal values than propane from Type I/II kerogen. The precursor for natural gases collected in this study is identified to be Type III kerogen. Comparing our data to calculated results for thermal cracking of Type III kerogen, we found that propane from the low-maturity gas reservoir in the Turpan Basin was generated via the i-propyl radical pathway, whereas propane from the Sulige tight gas reservoir in the Ordos Basin was formed via the n-propyl radical pathway. δ13Cterminal values covered a narrow range across basins, in contrast to δ13Ccentral. The terminal carbon position in propane is less impacted by microbial oxidation and more relevant to maturity levels and precursors. Thus, δ13Cterminal has a good potential to infer the origin and maturity level of natural gas. In examining post-generation processes, we proposed an improved identification strategy for microbial oxidation of natural gases, based on the position-specific carbon isotope distributions of propane. Samples from the Liaohe Depression of the Bohai Bay Basin and the Sichuan Basin were detected of post-generation microbial oxidation. Overall, position-specific carbon isotope composition of propane provides new insights into the generation mechanism and post-generation processes of natural gas in the geological period at the atomic level.

Abstract Background As a screening method, inaccuracies in noninvasive prenatal screening (NIPS) exist, which are often attributable to biological factors. One such factor is the history of transplantation. However, there are still limited reports on such NIPS cases. Methods We report an NIPS case of a pregnant woman who had received a stem cell transplant from a male donor. To determine the karyotype in the woman's original cell, we performed chromosome microarray analysis (CMA) on her postnatal blood and oral mucosa. To comprehensively estimate the cell‐free DNA (cfDNA) composition, we further performed standard NIPS procedures on the postnatal plasma. Moreover, we reviewed all published relevant NIPS case reports about pregnant women with transplantation history. Results NIPS showed a low‐risk result for common trisomies with a fetal fraction of 65.80%. CMA on maternal white blood cells showed a nonmosaic male karyotype, while the oral mucosa showed a nonmosaic female karyotype. The proportion of donor's cfDNA in postnatal plasma was 94.73% based on the Y‐chromosome reads ratio. The composition of cfDNA in maternal plasma was estimated as follows: prenatally, 13.60% maternal, 65.80% donor, and 20.60% fetal/placental, whereas postnatally, 5.27% maternal and 94.73% donor. Conclusions This study expanded our understanding of the influence of stem cell transplantation on NIPS, allowing us to optimize NIPS management for these women.

Sensorineural hearing loss (SNHL) is a prevalent condition in otolaryngology. A key obstacle is finding effective strategies for regenerating damaged cochlear hair cells in adult animals. A practical and reliable approach has been developed to create a superior cell source for stem cell transplantation in the inner ear to treat SNHL. Atoh1 is involved in the differentiation of neurons, intestinal secretory cells, and mechanoreceptors including auditory hair cells, and thus plays an important role in neurogenesis. Lentivirus-mediated transfection of bone marrow mesenchymal stem cells (BMSCs) was utilized to achieve stable expression of the essential transcription factor Atoh1, which is crucial for developing auditory hair cells without compromising cell survival. By manipulating the induction conditions through altering the cell growth environment using anti-adherent culture, the synergistic impact of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) was effectively applied to significantly improve the differentiation efficiency of bone marrow-derived mesenchymal stem cells (BMSC) into neural stem cells (NSCs) following Atoh1 transfection, thereby reducing the induction time. The study indicated that the newly proposed transdifferentiation method effectively transformed BMSCs into NSCs in a controlled environment, presenting a potential approach for stem cell transplantation to promote hair cell regeneration.

This study aims to investigate the effect of RU.521 on improving vascular endothelial injury in 14 acute lung injury patients. Serum myeloperoxidase, double-stranded DNA (dsDNA), IFN-β, and TNF-α levels of patients were detected by ELISA. Neutrophil extracellular traps were used to stimulate human venous endothelial cells (HUVEC). cGAS/STING pathway protein was detected by western blot. The protective effect of RU.521 on HUVEC was evaluated by CCK-8. The effects of RU.521 on cGAS/STING pathway expression were detected by PCR and western blot. The levels of myeloperoxidase and (dsDNA) in acute lung injury patients were significantly increased (p

BackgroundThe therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes.MethodsThis retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders.ResultsThe study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs.ConclusionIn conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes.

Unique fatty acid methyl esters (FAME) containing β‑hydroxy esters were produced using an engineered microorganism by glucose fermentation. This study investigated the properties of the unique FAME mixture both neat and in blends with conventional diesel, as well as properties of β‑hydroxy esters. The unique FAME blend contained relatively shorter-chain FAME (average fatty acid chain carbon number 14.6) with 58 % monounsaturated fatty acids and 9 % saturated and monounsaturated β‑hydroxy acid chains. The unique FAME had significantly lower distillation T90 (321 °C versus 352 °C) and higher cetane number (56.7 versus 52) compared to soy biodiesel. Cloud points were within method repeatability. Unexpectedly (because of the lack of methylene-interrupted double bonds), the unique FAME had low oxidation stability (1.5 h) as determined by Rancimat induction period. Stability could be improved through addition of commonly used antioxidants. We speculate that monounsaturated β‑hydroxy FAME may be the source of this instability. Blends with conventional diesel up to 50 vol% showed similar kinematic viscosity (within method repeatability) as blends of conventional FAME. The unique FAME had no effect on distillation T90 even at the 80 % blend level. A 30 vol% blend into conventional diesel had a Rancimat induction period of only 2 h, very nearly the same as the neat unique FAME sample. The addition of antioxidants produced blends of acceptable stability. Based on an assessment of the properties of individual β‑hydroxy FAME molecules, they have higher boiling point, higher cloud point, lower cetane number, and potentially lower storage stability than analogous FAME not having the β‑hydroxy group. Removing them from the fuel product in the production process may result in a biodiesel product with superior properties to what is on the market today.

BackgroundDiabetes mellitus is an independent risk factor for heart failure, and diabetes-induced heart failure severely affects patients’ health and quality of life. Cuproptosis is a newly defined type of programmed cell death that is thought to be involved in the pathogenesis and progression of cardiovascular disease, but the molecular mechanisms involved are not well understood. Therefore, we aimed to identify biomarkers associated with cuproptosis in diabetes mellitus-associated heart failure and the potential pathological mechanisms in cardiomyocytes.MaterialsCuproptosis-associated genes were identified from the previous publication. The GSE26887 dataset was downloaded from the GEO database.MethodsThe consistency clustering was performed according to the cuproptosis gene expression. Differentially expressed genes were identified using the limma package, key genes were identified using the weighted gene co-expression network analysis(WGCNA) method, and these were subjected to immune infiltration analysis, enrichment analysis, and prediction of the key associated transcription factors. Consistency clustering identified three cuproptosis clusters. The differentially expressed genes for each were identified using limma and the most critical MEantiquewhite4 module was obtained using WGCNA. We then evaluated the intersection of the MEantiquewhite4 output with the three clusters, and obtained the key genes.ResultsThere were four key genes: HSDL2, BCO2, CORIN, and SNORA80E. HSDL2, BCO2, and CORIN were negatively associated with multiple immune factors, while SNORA80E was positively associated, and T-cells accounted for a major proportion of this relationship with the immune system. Four enriched pathways were found to be associated: arachidonic acid metabolism, peroxisomes, fatty acid metabolism, and dorsoventral axis formation, which may be regulated by the transcription factor MECOM, through a change in protein structure.ConclusionHSDL2, BCO2, CORIN, and SNORA80E may regulate cardiomyocyte cuproptosis in patients with diabetes mellitus-associated heart failure through effects on the immune system. The product of the cuproptosis-associated gene LOXL2 is probably involved in myocardial fibrosis in patients with diabetes, which leads to the development of cardiac insufficiency.

BackgroundExchange transfusion therapy is a complex and invasive procedure with a high risk coefficient. This method involves replacing the entire blood of a child with fresh blood with double circulating blood volume in a short period, typically in 1–2 h. This procedure can cause the body's internal environment to be unstable, which can put newborns under a lot of stress. This stress can lead to many, including abnormal laboratory biochemical examination, low or high blood pressure, and apnea. There is also the possibility of secondary infection and, in severe cases, cardiac arrest. This study investigated the effects of Humidified high-flow nasal cannula (HHFNC) ventilation on hemodynamic stability and oxygenation during exchange transfusion in neonates. Furthermore, the effects on brain metabolism and salivary cortisol during exchange transfusion were also analyzed.MethodsIn this study, the control group consisted of 45 cases of children who underwent simple blood exchange between 1 May 2017, and 31 December 2019 control group. The observation group consisted of 33 cases of children who underwent blood exchange under HHFNC support between 1 January 2020, and 30 April 2022. The study compared various physiological parameters between the control and the observation group. These included blood gas analysis, pulmonary artery pressure, ejection fraction, invasive mean arterial pressure, heart rate, cerebral oxygenation, intestinal oxygenation, renal oxygenation, and duration of blood exchange. Furthermore, the study also compared the changes in brain metabolic and salivary cortisol indicators between the two groups of children.ResultsThe results did not reveal any significant difference in PH, PaO2, and duration of blood exchange between the control and the observation group. However, the observation group's invasive mean arterial pressure, ejection fraction, cerebral oxygenation, intestinal oxygenation, and renal oxygenation were higher than those of the control group. Furthermore, compared with the control group, the pulmonary artery pressure, heart rate, and PaCO2 were lower in the observation group. There was a statistically significant difference between the two groups of children in the relevant clinical indicators (total bilirubin, hemoglobin, SPO2, etc.) after exchange transfusion. After 1 h of blood exchange and after blood exchange, the salivary cortisol levels of the observation group were lower than the control group. The difference was statistically significant. The NAA/Cho and Cho/Cr values of the two groups of children were also significantly different.ConclusionDuring blood exchange, unstable hemodynamics substantially impact organ oxygenation. The results of this study suggest that HHFNC and specific ventilation pressure support can improve the respiratory rate and help maintain blood flow stability and organ oxygenation. This technique can also reduce adverse reactions caused by blood exchange, minimizing patient stress and reducing the impact on brain metabolism.

Abstract Background Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM. Methods RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood–brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein–protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results. Results RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 ~ -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway. Conclusion RPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.

Abstract Background Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. Methods In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. Results The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14–34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38–3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50–8.27) compared to non-AP IPMN. Conclusions AP is predictive of malignancy in patients with IPMN.

AbstractBackground Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages.Aim This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB.Methods This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction.Results Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p

Abstract Background Rabies is a widespread, fatal, infectious disease. Several antivirals against rabies virus (RABV) infection have been reported, but no approved, RABV-specific antiviral drugs that inhibit RABV infection in the clinic after symptom onset are available. Therefore, more effective drugs to reduce rabies fatalities are urgently needed. Bardoxolone methyl (CDDO-Me), an FDA-approved compound that has long been known as an antioxidant inflammatory modulator and one of the most potent nuclear factor erythroid-derived 2-like 2 (Nrf2) activators, protects myelin, axons, and CNS neurons by Nrf2 activation. Therefore, we investigated the potency of its anti-RABV activity in vitro. Methods The mouse neuroblastoma cell line Neuro2a (N2a) and three RABV strains of different virulence were used; the cytotoxicity and anti-RABV activity of CDDO-Me in N2a cells were evaluated by CCK-8 assay and direct fluorescent antibody (DFA) assay. Pathway activation in N2a cells infected with the RABV strains SC16, CVS-11 or CTN upon CDDO-Me treatment was evaluated by western blotting (WB) and DFA assay. Results CDDO-Me significantly inhibited infection of the three RABV strains of differing virulence (SC16, CVS-11 and CTN) in N2a cells. We also examined whether CDDO-Me activates the Nrf2-associated pathway upon infection with RABV strains of differing virulence. Nrf2, phosphorylated sequestosome (SQSTM1), SQSTM1, hemoglobin oxygenase (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) expression in N2a cells increased to varying degrees with CDDO-Me treatment, accompanied by Kelch-like ECH-associated protein 1 (Keap1) dissociation, upon infection with SC16, CVS-11 or CTN. The activation of SQSTM1 phosphorylation was significantly associated with the degradation of Keap-1 in CDDO-Me-treated N2a cells upon RABV infection. Furthermore, N2a cells pretreated with the Nrf2-specific inhibitor ATRA showed a significant decrease in HO-1 and NQO1 expression and a decrease in the anti-RABV efficacy of CDDO-Me. These inhibitory effects were observed upon infection with three RABV strains of differing virulence. Conclusion CDDO-Me inhibited RABV infection via Nrf2 activation, promoting a cytoprotective defense response in N2a cells. Our study provides a therapeutic strategy for RABV inhibition and neuroprotection during viral infection.

In this study, we aimed to determine and analyze the genetic differences of the FUT1 and FUT2 genes within an individual exhibiting the Para-Bombay phenotype. Standard serological tests were conducted to analyze the ABO phenotype. The amplification of FUT1 and FUT2 genes was conducted by polymerase chain reaction and amplicons were sequenced. The determination of the ABO genotype was conducted by sequencing exons 1 to 7 of the ABO gene. The Lewis phenotype was defined as Le(a−b+); Despite this, red blood cells (RBCs) did not show signs of A, B and H antigens using the serological method utilized in this study. However, Analyses of sequencing and cloning demonstrated the existence of a FUT1 mutation at position c.658C>T and an inactive allele FUT1*01N.06 (c.551_552delAG). Genetic testing for ABO blood types was subsequently determined to be ABO*B.01/ABO*B.01 (c.297A>G; c.526C>G; c.657C>T; c.703G>A; c.796C>A; c.803G>C; c.930G>A). Heterozygosity for indel and missense mutation within the coding region of FUT1 are likely to be responsible for development of the Para-Bombay phenotype.

Objective This study was conducted to investigate the effects of rumen-protected biotin (RPB) on growth performance, nutrient digestibility, nitrogen utilization and plasma biochemical parameters of Liaoning cashmere goats during the cashmere fiber growing period. Methods Sixteen 6-month-old Liaoning cashmere twin-doelings (24.8±1.20 kg) were allocated to 2 diet groups that were individually ad libitum fed 30% concentrate and 70% forage diet (dry matter [DM]) by a paired experimental design. Goats of the control group were fed the basal diet, while goats belonging to the RPB group were fed the basal diet with 10 mg RPB/d per animal. The duration of the experiment was 16 weeks with two 8-week periods. Digestibility was determined at weeks 7 and 15, and other measures were taken every four weeks. Results Compared with the control group, the average daily gain of the RPB group increased by 10.94% (p

Abstract Aim To explore the psychological experience and coping methods of nurses exposed to workplace violence and to propose measures to prevent and control workplace violence and provide psychological assistance for health workers. Design We adopted a phenomenological qualitative design. Twelve nurses in intensive care units assisting in Wuhan who experienced workplace violence during the COVID‐19 outbreak were selected using purposeful sampling. Data were collected through semi‐structured individual telephone interviews and analysed using Colaizzi's 7‐step method. Results Analysis revealed three main categories including “Full of negative emotions”, “Facing challenges and danger” and “Coping methods”. The subjects experienced stress, fear, anger, helplessness, disappointment, sympathy and job burnout after suffering from workplace violence. The coping methods for workplace violence mainly included seeking support and help, escaping, making explanations, exercising tolerance and confronting the issue. Patient or Public Contribution No patient or public contribution since nurses' experiences were explored.

Substation equipment defect detection has always played an important role in equipment operation and maintenance. However, the task scenarios of substation equipment defect detection are complex and different. Recent studies have revealed issues such as a significant missed detection rate for small-sized targets and diminished detection precision. At the same time, the current mainstream detection algorithms are highly complex, which is not conducive to deployment on resource-constrained devices. In view of the above problems, a small target and lightweight substation main scene equipment defect detection algorithm is proposed: Efficient Attentional Lightweight-YOLO (EAL-YOLO), which detection accuracy exceeds the current mainstream model, and the number of parameters and floating point operations (FLOPs) are also advantageous. Firstly, the EfficientFormerV2 is used to optimize the model backbone, and the Large Separable Kernel Attention (LSKA) mechanism has been incorporated into the Spatial Pyramid Pooling Fast (SPPF) to enhance the model’s feature extraction capabilities; secondly, a small target neck network Attentional scale Sequence Fusion P2-Neck (ASF2-Neck) is proposed to enhance the model’s ability to detect small target defects; finally, in order to facilitate deployment on resource-constrained devices, a lightweight shared convolution detection head module Lightweight Shared Convolutional Head (LSCHead) is proposed. Experiments show that compared with YOLOv8n, EAL-YOLO has improved its accuracy by 2.93 percentage points, and the mAP50 of 12 types of typical equipment defects has reached 92.26%. Concurrently, the quantity of FLOPs and parameters has diminished by 46.5% and 61.17% respectively, in comparison with YOLOv8s, meeting the needs of substation defect detection.

Butterflies serve as valuable indicators of urban ecosystem quality. Due to their accessibility, they also provide urban residents with essential opportunities to connect with nature, fulfilling social functions such as education and recreation, which significantly contribute to city dwellers’ physical and mental well-being. Urban mountain parks are critical habitats for butterflies; analyzing their spatial and temporal distribution and the impact of plant elements is crucial for enhancing plant landscape quality and butterfly diversity. The main results were as follows: (1) A monthly butterfly survey was carried out over the course of a year in the seven urban mountain parks of Fuzhou City. This survey recorded 46 species of butterflies from 36 genera across 7 families, totaling 2506 butterflies. (2) Among the seven habitat types analyzed, TS-, T-, and SG-habitats exhibited elevated levels of butterfly diversity, richness, abundance, and evenness. There were variations in butterfly evenness, diversity, richness, and abundance observed between these habitats. With the exception of N-habitat, there was a consistent seasonal pattern in butterfly diversity across different habitat types. (3) Butterfly diversity and abundance were significantly correlated with vegetation habitat factors across the tree, shrub, and herb layers. Multiple regression modeling using the Akaike information criterion revealed that arbor layer vegetation factors were present in the top four models for butterfly diversity, richness, abundance, and evenness. (4) The quality assessment of different habitat types ranked habitats as follows: TS-habitat > SG-habitat > TSG-habitat > T-habitat > TG-habitat > G-habitat = N-habitat.

Accurate and early diagnosis of monkeypox virus (MPXV) is crucial for controlling epidemics and treating affected individuals promptly. This study aimed to assess the analytical and clinical performance of the MolecisionTM Monkeypox Virus qPCR Assay, Biorain Monkeypox Virus ddPCR Assay, and MAGLUMI® Monkeypox Virus Ag (chemiluminescence immunoassay, CLIA) Assay. Additionally, it aimed to compare the clinical application of antigen and nucleic acid assays to offer insights into using commercial monkeypox assay kits. Specimens from 117 clinical patients, serial diluted virus cell culture supernatant, and artificially created positive samples were tested to evaluate the performance of these assay kits for MPXV diagnostics. The Biorain Monkeypox Virus ddPCR Assay had a limit of detection (LoD) of 3.89 CCID50/mL, while the MolecisionTM Monkeypox Virus qPCR Assay had an LoD of 15.55 CCID50/mL. The MAGLUMI® Monkeypox Virus Ag (CLIA) Assay had an LoD of 0.500 pg/mL. The accuracy of the MolecisionTM Monkeypox Virus qPCR Assay was comparable to the Biorain Monkeypox Virus ddPCR Assay, and the MAGLUMI® Monkeypox Virus Ag (CLIA) Assay demonstrated high sensitivity. The specificity of all three MPXV diagnostic assays for clinical specimens with potential cross-reacting substances was 100%. In conclusion, this study provides valuable insights into the clinical application of monkeypox assays, supporting efforts to mitigate and control the spread of monkeypox.

In response to biomedical imperatives, a novel approach is presented for the endovascular management of atherosclerosis. This approach is grounded in the electrohydraulic effect of a precisely controlled low-energy pulse discharge system, coupled with sequential control within the incomplete discharge electrode, to generate shockwaves aimed at softening blood vessels and rupturing calcified plaques. Theoretical analysis encompassed circuit design, control timing, and operational processes, while experimental investigations demonstrated precise control of non-oscillation and incomplete discharge by adjusting key parameters. Utilizing a 3 kV DC high-voltage power supply, a 220 nF capacitor, and two sets of 3.3 Ω resistors in parallel, with pin–plate electrodes as the load for discharge in normal saline, resulted in a 1 kV reduction in voltage across the capacitor and a peak current of 170 A. Energy release occurred through non-oscillatory and incomplete discharge, effectively generating shockwaves with peak pressures of 5–10 MPa at distances of 1–2 mm from the discharge center to treat calcified lesions. Compared with the existing intravascular lithotripsy devices, the shockwave system realizes accurate control of discharge energy by adjusting the turn-off time of incomplete discharge so as to realize accurate control of shockwave energy. Doctors can choose different intensities of shockwaves according to different degrees of calcification in the treatment process so as to minimize the discomfort caused by shockwaves and improve safety. Valuable insights are provided for intravascular lithotripsy devices in engineering.

IntroductionIn urban traffic management, the timely detection of road faults plays a crucial role in improving traffic efficiency and safety. However, conventional methods often fail to fully leverage the information from road topology and traffic data.MethodsTo address this issue, we propose an innovative detection system that combines Artificial Neural Networks (ANNs), specifically Graph Convolutional Networks (GCN), Bidirectional Gated Recurrent Units (BiGRU), and self-attention mechanisms. Our approach begins by representing the road topology as a graph and utilizing GCN to model it. This allows us to learn the relationships between roads and capture their structural dependencies. By doing so, we can effectively incorporate the spatial information provided by the road network. Next, we employ BiGRU to model the historical traffic data, enabling us to capture the temporal dynamics and patterns in the traffic flow. The BiGRU architecture allows for bidirectional processing, which aids in understanding the traffic conditions based on both past and future information. This temporal modeling enhances our system's ability to handle time-varying traffic patterns. To further enhance the feature representations, we leverage self-attention mechanisms. By combining the hidden states of the BiGRU with self-attention, we can assign importance weights to different temporal features, focusing on the most relevant information. This attention mechanism helps to extract salient features from the traffic data. Subsequently, we merge the features learned by GCN from the road topology and BiGRU from the traffic data. This fusion of spatial and temporal information provides a comprehensive representation of the road status.Results and discussionsBy employing a Multilayer Perceptron (MLP) as a classifier, we can effectively determine whether a road is experiencing a fault. The MLP model is trained using labeled road fault data through supervised learning, optimizing its performance for fault detection. Experimental evaluations of our system demonstrate excellent performance in road fault detection. Compared to traditional methods, our system achieves more accurate fault detection, thereby improving the efficiency of urban traffic management. This is of significant importance for city administrators, as they can promptly identify road faults and take appropriate measures for repair and traffic diversion.

To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1β, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1β mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1β, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1β after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.

Background: Previous studies have shown that endoplasmic reticulum stress (ERS) -induced apoptosis is involved in the pathogenesis of dilated cardiomyopathy (DCM). However, the molecular mechanism involved has not been fully characterized.Results: In total, eight genes were obtained at the intersection of 1,068 differentially expressed genes (DEGs) from differential expression analysis between DCM and healthy control (HC) samples, 320 module genes from weighted gene co-expression network analysis (WGCNA), and 2,009 endoplasmic reticulum stress (ERGs). These eight genes were found to be associated with immunity and angiogenesis. Four of these genes were related to apoptosis. The upregulation of MX1 may represent an autocompensatory response to DCM caused by a virus that inhibits viral RNA and DNA synthesis, while acting as an autoimmune antigen and inducing apoptosis. The upregulation of TESPA1 would lead to the dysfunction of calcium release from the endoplasmic reticulum. The upregulation of THBS4 would affect macrophage differentiation and apoptosis, consistent with inflammation and fibrosis of cardiomyocytes in DCM. The downregulation of MYH6 would lead to dysfunction of the sarcomere, further explaining cardiac remodeling in DCM. Moreover, the expression of genes affecting the immune micro-environment was significantly altered, including TGF-β family member. Analysis of the co-expression and competitive endogenous RNA (ceRNA) network identified XIST, which competitively binds seven target microRNAs (miRNAs) and regulates MX1 and THBS4 expression. Finally, bisphenol A and valproic acid were found to target MX1, MYH6, and THBS4.Conclusion: We have identified four ERS-related genes (MX1, MYH6, TESPA1, and THBS4) that are dysregulated in DCM and related to apoptosis. This finding should help deepen understanding of the role of endoplasmic reticulum stress-induced apoptosis in the development of DCM.

IntroductionIschemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed.MethodsIn this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case–control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments.ResultsA total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis.DiscussionIn conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

Abstract Aim The aim was to investigate the prevalence of, and factors related to frailty, together with early clinical outcomes, in hospitalized older patients with valvular heart disease (VHD) in China. Design A prospective observational cohort study was conducted. Methods A validated prospective survey was conducted to assess the prevalence of frailty, factors associated with it, and early clinical outcomes in hospitalized older patients with VHD, utilizing Fried's criterion. A total of 207 consecutive participants aged 65 years and older who underwent cardiac surgery were included in the study, spanning from September 2021 to December 2021. Results Frailty was detected in 78 patients (37.7%). Patients with multimorbidity, a New York Heart Association (NYHA) class of III/IV, or masticatory dysfunction had a greater incidence of frailty (p

IntroductionAtopic dermatitis (AD) is one of the most common inflammatory skin diseases. Skin microecological imbalance is an important factor in the pathogenesis of AD, but the underlying mechanism of its interaction with humans remains unclear.Methods16S rRNA gene sequencing was conducted to reveal the skin microbiota dynamics. Changes in skin metabolites were tracked by LC–MS metabolomics. We then explored the potential mechanism of interaction by analyzing the correlation between skin bacterial communities and metabolites in corresponding skin-associated samples.ResultsSamples from 18 AD patients and 18 healthy volunteers (HVs) were subjected to 16S rRNA gene sequencing and LC–MS metabolomics. AD patients had dysbiosis of the skin bacterial community with decreased species richness and evenness. The relative abundance of the genus Staphylococcus increased significantly in AD, while the abundances of the genera Propionibacterium and Brevundimonas decreased significantly. The relative abundance of the genera Staphylococcus in healthy females was significantly higher than those in healthy males, while it showed no difference in AD patients with or without lesions. The effects of AD status, sex and the presence or absence of rashes on the number of differentially abundant metabolites per capita were successively reduced. Multiple metabolites involved in purine metabolism and phenylalanine metabolism pathways (such as xanthosine/xanthine and L-phenylalanine/trans-cinnamate) were increased in AD patients. These trends were much more obvious between female AD patients and female HVs. Spearman correlation analysis revealed that the genus Staphylococcus was positively correlated with various compounds involved in phenylalanine metabolism and purine metabolic pathways. The genera Brevundimonas and Lactobacillus were negatively correlated with various compounds involved in purine metabolism, phenylalanine metabolism and sphingolipid signaling pathways.DiscussionWe suggest that purine metabolism and phenylalanine metabolism pathway disorders may play a certain role in the pathogenic mechanism of Staphylococcus aureus in AD. We also found that females are more likely to be colonized by the genus Staphylococcus than males. Differentially abundant metabolites involved in purine metabolism and phenylalanine metabolism pathways were more obvious in female. However, we should notice that the metabolites we detected do not necessarily derived from microbes, they may also origin from the host.

Introduction Transcatheter aortic valve replacement (TAVR) is a standard treatment for aortic stenosis, particularly in older adults. Reduced exercise capacity and frailty significantly impact outcomes in TAVR patients, yet current management lacks strategies to address these issues. This study aims to assess the effectiveness of home-based mobile-guided exercise-based cardiac rehabilitation in TAVR patients, led by a multidisciplinary team with clear progression milestones.Methods and analysis The study involves 90 patients aged 60–89 in a single centre who will be randomised to a 3-month novel multidomain exercise intervention or routine care. Outcome assessors will be blinded towards group allocation. The primary outcome is the 6-min walk distance at month 3. The secondary outcomes include the 6-min walk distance at month 6, physical function measured by total Short Physical Performance Battery score and exercise adherence measured by the Exercise Adherence Rating Scale at months 3 and 6. Additional outcome measures, including rehospitalisations, death, handgrip strength, frailty (Fried Criteria and Essential Toolset), cognitive function (Mini-Mental State Examination), quality of life (EuroQol 5-Dimension 5-Level), nutritional status (Mini-Nutritional Assessment), anxiety (General Anxiety Disorder-7), depression (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), functional capacity (Duke Activity Status Index), clinical indices (body mass index, symptoms, signs, left ventricular ejection fraction (LVEF), N-Terminal Pro-Brain Natriuretic Peptide, etc) and social support (Lubben Social Network Scale-6), along with comprehensive cost analysis, enhance the study’s significance. The study’s findings hold crucial implications for crafting an effective exercise-focused cardiac rehabilitation strategy for TAVR patients. Community implementation not only deepens understanding but also fosters the potential integration of exercise-based cardiac rehabilitation into self-care, promising enhanced patient adherence and overall cardiovascular health management.Ethics and dissemination Ethical approval was obtained from the Zhongshan Hospital, Fudan University Ethics Committee (B2022-062R). Results will be disseminated to local stakeholders and the research community through publications and conferences.Trial registration number NCT05989594