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The direct sequencing of the Kit cDNA obtained from mutant mice was used to reveal the molecular nature of the W−3Bao ENU-induced mutation. There was a T to A transversion at the 441st nucleotide in the W−3Bao open reading frame (ORF), which introduced a pre-mature termination codon at residue 147. The gross embryonic development, hematopoiesis and spermatogenesis were examined in the mutant mice. There was no visible difference among the W−3Bao/+, W−3Bao/3Bao and wild type embryos before embryonic day 12.5. W−3Bao/3Bao embryos appeared pale after E14.5 and dwarf after E16.5. An extremely low level of hematochrome and large red blood cells were found in W−3Bao/3Bao 18.5 days old embryos, leading to the stillbirth of the homozygotes. In 18.5 days old embryos the spermatogonia of W−3Bao/3Bao embryos did not migrate to the contorted seminiferous tubules properly, but instead were found in the interstitial tissue. The spermatogonia of W−3Bao/+ or W+/+ mice were present in both the interstitial tissue and contorted seminiferous tubules. In the adult male hetereozygotes, there are contorted seminiferous tubules with no spermatogonia, suggesting that the migration defect was dominant. In female W−3Bao/3Bao ovaries, primordial follicles were absent while primordial follicles appeared clearly in the ovaries of W−3Bao/+ or W+/+ mice. With a nonsense mutation in the Kit gene, W−3Bao/+ mice show white spotting and an abnormal development of the contorted seminiferous tubules and W−3Bao/3Bao mice are stillborn due to severe macrocytic anemia, and have abnormal genital glands in both the male and female. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Deep sequencing reveals an association between HIV-1 subtype C mutations in gp41 MPER epitopes and mother-to-child transmission," by L. Yin and colleagues is presented.

Objectives: This study was designed to compare the clinical data of vesicoureteral reflux (VUR) in children with and without an allergic constitution., Methods: The clinical data of patients hospitalized with VUR due to a urinary tract infection (UTI) between September 1, 2019, and December 31, 2020, were retrospectively analyzed. The patients were divided into two groups: an anallergic constitution group (AC group) and a non-allergic constitution (NAC group), and their UTIs and VUR were compared at baseline and during the follow-up period., Results: (1) Between September 1, 2019, and December 31, 2020, a total of 284 children were hospitalized at Shengjing Hospital Affiliated to China Medical University due to a UTI. These children included 37 cases with primary VUR and 247 cases without VUR (including 59 cases of non-VUR urinary malformation). The proportion of children with an allergic constitution was significantly higher in the patients with VUR than it was in those without VUR or with other urinary malformations (72.97% vs. 48.18% vs. 50.85%, P = 0.005, 0.032). (2) At baseline, the levels of immunoglobulin and immunoglobulin E in the AC group were significantly higher than those in the NAC group (P = 0.042, 0.017). (3) During the follow-up period, the number of recurrent UTI cases in the AC group was significantly higher than that in the NAC group (0.70 ± 0.91 vs. 0.10 ± 0.32, P= 0.005). The difference between the two groups in the VUR remission rate was not statistically significant (40% vs. 50%, P = 0.563). (4) During the follow-up period, the differences in the remission rates of recurrent UTIs and VUR in the two groups were not statistically significant., Conclusions: The incidence of having an allergic constitution is high in patients with VUR, and patients with an allergic constitution present with a higher frequency of recurrent UTIs., (© 2024. The Author(s).)

Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12-16 weeks), GDM patients (24-28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12-16 and 24-28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM., (© 2024. The Author(s).)

Background: In clinical oncology practice, patient-reported outcomes (PROs) are essential for assessing the symptom burden, quality of life, and psychological status of patients. However, there remains a gap between the use of PROs in an oncologic setting and its implementation. Furthermore, numerous reviews in PRO implementation are often based on one particular technology, setting, or health condition, making it difficult to obtain a comprehensive and coherent summary of available evidence to help plan and undertake implementation. This systematic review aims to identify and integrate enablers and barriers to PRO implementation through the comprehensive framework for implementation research (CFIR) to provide a reference for implementing patient-reported outcomes management in oncology settings., Methods: This review strictly observed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed, Web of Science, CINAHL, Embase, and PsycINFO databases were systematically searched using a three-step search strategy. The search was limited from the inception of each database to April 2024. Articles describing facilitators and barriers to implementing PROs in clinical oncology practice were included. Two researchers screened the literature independently, and the quality assessment of cross-sectional, qualitative, and mixed studies was completed using the critical appraisal tools recommended by Joanna Briggs Institute (JBI) and the mixed methods assessment tool, respectively. Basic information about the included studies and determinants affecting PRO implementation was extracted, and coding categorization of facilitators and barriers was completed based on the 48 constructs provided by the CFIR framework., Results: We included 30 studies from 5,649 search results, including 25 original and 5 review studies. The quality of the literature for qualitative studies was generally good, and the quality for quantitative and mixed studies was assessed as fair. We identified 52 facilitators and 50 barriers in the included literature, covering the domains used in the CFIR framework and 39 constructs, mainly including "Innovation Evidence-Base", "Innovation Complexity", "Innovation Design", "Structural Characteristics", "Compatibility", "Incentive Systems", "Access to Knowledge & Information", "Innovation Deliverers", "Innovation Recipients", and "Planning"., Conclusions: This systematic review integrated facilitators and barriers affecting PRO implementation in routine oncology clinical practice settings and categorized them through the CFIR framework. These influencing factors should be fully considered in future clinical practice to ensure the successful implementation of PROs., Trial Registration: It has been registered prospectively in PROSPERO under the registration number 42024532983., (© 2024. The Author(s).)

Background: Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable OC., Methods: Eligible patients with stage III-IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m 2 , day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3-6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations)., Results: Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7-84.7%). With a median follow-up of 17.5 (range 0.7-36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7-92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8-23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3-4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively., Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting., Trial Registration: ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019., (© 2024. The Author(s).)

Background: Evidence to support risk stratification in Eisenmenger syndrome (ES) is still very limited. We hypothesized that biventricular longitudinal strain analysis could have potential prognostic value in ES., Methods: We prospectively enrolled fifty-seven consecutive ES patients with post-tricuspid shunt who underwent both cardiovascular magnetic resonance (CMR) and right heart catheterization between June 2013 and March 2022. Biventricular longitudinal strains were evaluated by CMR feature-tracking analysis. The composite endpoint included all-cause mortality and re-admission for heart failure or hemoptysis. Cox regression analysis, Kaplan-Meier curves, and C-index were employed to assess the relationship between biventricular longitudinal strain and prognosis., Results: During a median follow-up of 33 months (interquartile range: 12-50), 20 (35.1%) patients reached the composite endpoint. Patients with composite endpoints had significantly lower absolute values of left ventricular global longitudinal strain (LV GLS) and right ventricular free wall longitudinal strain (RV FWLS) than patients without composite endpoints (p < 0.05). Multivariate Cox regression analysis demonstrated that LV GLS and RV FWLS were independent predictors for composite endpoints (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.08-1.75, p = 0.010 and HR: 1.19, 95% CI: 1.01-1.41, p = 0.042). Kaplan-Meier analysis indicated that patients with both lower absolute values of LV GLS and RV FWLS were more likely to be at an even higher risk of composite endpoints (p < 0.001). Furthermore, the combined addition of LV GLS and RV FWLS provided incremental value for the prognostic model including clinical parameters and biventricular ejection fraction (C-index increased from 0.75 to 0.86, p = 0.004)., Conclusion: Impaired biventricular longitudinal strains improved prognostic prediction of ES patients with post-tricuspid shunt., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests Not applicable., (Copyright © 2024. Published by Elsevier Inc.)

Diabetic nephropathy affects a significant proportion of individuals with diabetes, and its progression often leads to cardiovascular disease and infections before the need for renal replacement therapy arises. Empagliflozin has been shown to have various protective effects in cardiovascular disease studies, such as improving diabetic myocardial structure and function, and reducing myocardial oxidative stress. However, the impact of empagliflozin on cardiac protein expression and signaling pathways has not been comprehensively analyzed. To address this gap, we conducted proteome analysis to identify specific protein markers in cardiac tissue from the diabetes model group, including Myh7, Wdr37, Eif3k, Acot1, Acot2, Cat, and Scp2, in cardiac tissue from the diabetes model group. In our drug model, empagliflozin primarily modulates the fat-related metabolic signaling pathway within the heart. Empagliflozin downregulated the protein expression levels of ACOX1, ACADVL and CPT1A in the model group. Overall, our findings demonstrate that empagliflozin provides cardiac protection by targeting metabolic signaling pathways, particularly those related to fat metabolism. Moreover, the identification of cardiac biomarkers in a mouse model of diabetic nephropathy lays the foundation for further exploration of disease biomarkers in cardiac tissue., (© 2024. The Author(s).)

Early screening methods for the thyroid gland include palpation and imaging. Although palpation is relatively simple, its effectiveness in detecting early clinical signs of the thyroid gland may be limited, especially in children, due to the shorter thyroid growth time. Therefore, this constitutes a crucial foundational work. However, accurately determining the location and size of the thyroid gland in children is a challenging task. Accuracy depends on the experience of the ultrasound operator in current clinical practice, leading to subjective results. Even among experts, there is poor agreement on thyroid identification. In addition, the effective use of ultrasound machines also relies on the experience of the ultrasound operator in current clinical practice. In order to extract sufficient texture information from pediatric thyroid ultrasound images while reducing the computational complexity and number of parameters, this paper designs a novel U-Net-based network called DC-Contrast U-Net, which aims to achieve better segmentation performance with lower complexity in medical image segmentation. The results show that compared with other U-Net-related segmentation models, the proposed DC-Contrast U-Net model achieves higher segmentation accuracy while improving the inference speed, making it a promising candidate for deployment in medical edge devices in clinical applications in the future., (© 2024. The Author(s).)

Background: Whole genome sequencing (WGS) is becoming increasingly prevalent for molecular diagnosis, staging and prognosis because of its declining costs and the ability to detect nearly all genes associated with a patient's disease. The currently widely accepted variant calling pipeline, GATK, is limited in terms of its computational speed and efficiency, which cannot meet the growing analysis needs., Results: Here, we propose a fast and accurate DNASeq variant calling workflow that is purely composed of tools from LUSH toolkit. The precision and recall measurements indicate that both the LUSH and GATK pipelines exhibit high levels of consistency, with precision and recall rates exceeding 99% on the 30x NA12878 dataset. In terms of processing speed, the LUSH pipeline outperforms the GATK pipeline, completing 30x WGS data analysis in just 1.6 h, which is approximately 17 times faster than GATK. Notably, the LUSH&#95;HC tool completes the processing from BAM to VCF in just 12 min, which is around 76 times faster than GATK., Conclusion: These findings suggest that the LUSH pipeline is a highly promising alternative to the GATK pipeline for WGS data analysis, with the potential to significantly improve bedside analysis of acutely ill patients, large-scale cohort data analysis, and high-throughput variant calling in crop breeding programs. Furthermore, the LUSH pipeline is highly scalable and easily deployable, allowing it to be readily applied to various scenarios such as clinical diagnosis and genomic research., (© 2024. The Author(s).)

Background: Issues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study., Methods: Thirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results., Results: The alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R 2  = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter&#95;gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples ( P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050)., Conclusions: These findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients., Chinese Clinical Trial Registry: No. ChiCTR2300067507. Registered on January 10,2023 retrospectively., (© 2024. The Author(s).)

Introduction: Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to β-amyloid (Aβ) and tau pathology in Alzheimer's disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches., Methods: We employed heparin-affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to enrich HBPs from plasma obtained from AD (n = 62) and control (n = 47) samples. These profiles were then correlated to Aβ, tau and phosphorylated tau (pTau) CSF biomarkers and plasma pTau181 from the same individuals, as well as a consensus brain proteome network to assess the overlap with AD brain pathophysiology., Results: Heparin enrichment from plasma was highly reproducible, enriched well-known HBPs like APOE and thrombin, and depleted high-abundant proteins such as albumin. A total of 2865 proteins, spanning 10 orders of magnitude in abundance, were measured across 109 samples. Compared to the consensus AD brain protein co-expression network, we observed that specific plasma proteins exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes, highlighting the complex interplay between the two compartments. Elevated proteins in AD plasma, when compared to controls, included members of the matrisome module in brain that accumulate with Aβ deposits, such as SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB, and the APOE4 proteoform. Additionally, heparin-enriched proteins in plasma demonstrated significant correlations with conventional AD CSF biomarkers, including Aβ, total tau, pTau, and plasma pTau181. A panel of five plasma proteins classified AD from control individuals with an area under the curve (AUC) of 0.85. When combined with plasma pTau181, the panel significantly improved the classification performance of pTau181 alone, increasing the AUC from 0.93 to 0.98. This suggests that the heparin-enriched plasma proteome captures additional variance in cognitive dementia beyond what is explained by pTau181., Conclusion: These findings support the utility of a heparin-affinity approach coupled with TMT-MS for enriching amyloid-associated proteins, as well as a wide spectrum of plasma biomarkers that reflect pathological changes in the AD brain., (© 2024. The Author(s).)

Introduction: When young children experience recurrent respiratory infections, caregivers face the challenge of preventing new episodes whilst maintaining close rapport with their children. Pediatric massage, such as pediatric Tuina, entails soft massage of the skin, administered by trained providers. This non-pharmaceutical measure is used to prevent new respiratory infections in China. The aim of this study is to deepen our understanding of caregivers' experiences and perceptions of providing pediatric Tuina treatment to their children with recurrent respiratory tract infections., Methods: A qualitative study, based on semi-structured interviews, was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist. Sixteen mothers from Southern China, whose children had received pediatric Tuina for recurrent respiratory tract infections, participated online. Analysis was conducted according to the principles of reflexive thematic analysis, using the NVivo qualitative research software., Results: The overarching theme was "Fostering embodied care with children". Caregivers assessed pediatric Tuina by hearing others' experiences of pediatric Tuina, as well as observing the manipulations on their child's body and their bodily reactions during pediatric Tuina sessions. Caregivers also closely observed children's bodily changes after pediatric Tuina sessions. Embodied attachment between children and adults was nurtured through the pediatric Tuina. Compared to other treatments or medical consultations, children were more relaxed and more involved in embodied care, which involved direct skin touching and verbal communication from the pediatric Tuina provider. Children also took the initiative to bring pediatric Tuina into their family life, by asking caregivers to perform it on them and mimicking the manipulations on the caregivers' hand., Conclusions: Pediatric Tuina served as a means of interaction between children and adults, fostering an embodied care on both a physical and emotional level. Beyond its potentially preventive effect on recurrent respiratory tract infections, pediatric Tuina could be a support for parents of children with recurrent or chronic disease at home., (© 2024. The Author(s).)

Background: Lodging, a crucial agronomic trait linked to soybean yield, poses a significant challenge in soybean production. Nevertheless, there has been less research on soybean lodging compared to other important agronomic traits, hindering progress in breeding high-yield soybeans. Our goals were to investigate lodging, pinpoint quantitative trait loci (QTL) linked to lodging, and forecast potential candidate genes linked to this trait. To achieve this, we employed a recombinant inbred line (RIL) population derived from a cross between Guizao 1 and B13 (GB) across various environments., Results: The lodging score of the RIL population was found to be significantly positively correlated with flowering time, maturity time, plant height, number of main stem nodes, stem diameter, and internode length, with correlation coefficients ranging from 0.457 to 0.783. A total of 84 QTLs associated with soybean lodging and related traits were identified using the GB population. The contribution of phenotypic variance ranged from 1.26 to 66.87%, with LOD scores ranging from 2.52 to 69.22. Additionally, within these QTLs, a stable major QTL associated with lodging was newly discovered in the GB population. Out of the ten major QTLs associated with other related traits, nine of them were situated within the qLD-4-1 interval of the major lodging score locus, displaying phenotypic variations ranging from 12.10 to 66.87%. Specific alterations in gene expression were revealed through the analysis of resequencing data from the two parental lines, potentially indicating their significant roles in lodging. Subsequently, it was determined through qRT-PCR that four genes are likely to be the major genes controlling soybean lodging., Conclusions: This study's findings offer valuable insights into the genetic underpinnings of soybean lodging resistance traits. By comprehending the potential genetic factors associated with lodging, this research lays the groundwork for breeding high-yield soybeans with improved lodging resistance., (© 2024. The Author(s).)

Background: Patients with tuberous sclerosis complex (TSC) develop renal cysts and/or angiomyolipomas (AMLs) due to inactive mutations of either TSC1 or TSC2 and consequential mTOR hyperactivation. The molecular events between activated mTOR and renal cysts/AMLs are still largely unknown., Methods: The mouse model of TSC-associated renal cysts were constructed by knocking out Tsc2 specifically in renal tubules (Tsc2 f/f ; ksp-Cre). We further globally deleted PRAS40 in these mice to investigate the role of PRAS40. Tsc2 -/- cells were used as mTOR activation model cells. Inhibition of DNA methylation was used to increase miR-142-3p expression to examine the effects of miR-142-3p on PRAS40 expression and TSC-associated renal cysts., Results: PRAS40, a component of mTOR complex 1, was overexpressed in Tsc2-deleted cell lines and mouse kidneys (Tsc2 f/f ; ksp-Cre), which was decreased by mTOR inhibition. mTOR stimulated PRAS40 expression through suppression of miR-142-3p expression. Unleashed PRAS40 was critical to the proliferation of Tsc2 -/- cells and the renal cystogenesis of Tsc2 f/f ; ksp-Cre mice. In contrast, inhibition of DNA methylation increased miR-142-3p expression, decreased PRAS40 expression, and hindered cell proliferation and renal cystogenesis., Conclusions: Our data suggest that mTOR activation caused by TSC2 deletion increases PRAS40 expression through miR-142-3p repression. PRAS40 depletion or the pharmacological induction of miR-142-3p expression impaired TSC2 deficiency-associated renal cystogenesis. Therefore, harnessing mTOR/miR-142-3p/PRAS40 signaling cascade may mitigate hyperactivated mTOR-related diseases., (© 2024. The Author(s).)

Background: Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms., Methods: This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1β, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI., Results: There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI)., Conclusions: LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque., Trial Registration: ChiCTR2200058529; Date of registration: 2022-04-10., (© 2024. The Author(s).)

Background: The pathogenesis of osteoarthritis (OA) involves the progressive degradation of articular cartilage. Exosomes derived from mesenchymal stem cells (MSC-EXOs) have been shown to mitigate joint pathological injury by attenuating cartilage destruction. Optimization the yield and therapeutic efficacy of exosomes derived from MSCs is crucial for promoting their clinical translation. The preconditioning of MSCs enhances the therapeutic potential of engineered exosomes, offering promising prospects for application by enabling controlled and quantifiable external stimulation. This study aims to address these issues by employing pro-inflammatory preconditioning of MSCs to enhance exosome production and augment their therapeutic efficacy for OA., Methods: The exosomes were isolated from the supernatant of infrapatellar fat pad (IPFP)-MSCs preconditioned with a pro-inflammatory factor, TNF-α, and their production was subsequently quantified. The exosome secretion-related pathways in IPFP-MSCs were evaluated through high-throughput transcriptome sequencing analysis, q-PCR and western blot analysis before and after TNF-α preconditioning. Furthermore, exosomes derived from TNF-α preconditioned IPFP-MSCs (IPFP-MSC-EXOs TNF-α ) were administered intra-articularly in an OA mouse model, and subsequent evaluations were conducted to assess joint pathology and gait alterations. The expression of proteins involved in the maintenance of cartilage homeostasis within the exosomes was determined through proteomic analysis., Results: The preconditioning with TNF-α significantly enhanced the exosome secretion of IPFP-MSCs compared to unpreconditioned MSCs. The potential mechanism involved the activation of the PI3K/AKT signaling pathway in IPFP-MSCs by TNF-α precondition, leading to an up-regulation of autophagy-related protein 16 like 1(ATG16L1) levels, which subsequently facilitated exosome secretion. The intra-articular administration of IPFP-MSC-EXOs TNF-α demonstrated superior efficacy in ameliorating pathological changes in the joints of OA mice. The preconditioning of TNF-α enhanced the up-regulation of low-density lipoprotein receptor-related protein 1 (LRP1) levels in IPFP-MSC-EXOs TNF-α , thereby exerting chondroprotective effects., Conclusion: TNF-α preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of IPFP-MSCs derived exosomes in the treatment of OA., (© 2024. The Author(s).)

Background: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells., Methods: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures., Results: We found intermediate cells expressing AR + PSA + CK8 + CK5 + in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR + PSA + CK8 + CK18 + ), basal (CK5 + P63 + ), intermediate (IVL + ), and stem cell (CK4 + CK13 + PSCA + SOX2 + ) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro., Conclusions: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine., (© 2024. The Author(s).)

Background: Camptothecin (CPT) is one of the frequently used small chemotherapy drugs for treating hepatocellular carcinoma (HCC), but its clinical application is limited due to severe toxicities and acquired resistance. Combined chemo-gene therapy has been reported to be an effective strategy for counteracting drug resistance while sensitizing cancer cells to cytotoxic agents. Thus, we hypothesized that combining CPT with miR-145 could synergistically suppress tumor proliferation and enhance anti-tumor activity., Methods: Lactobionic acid (LA) modified lipid nanoparticles (LNPs) were developed to co-deliver CPT and miR-145 into asialoglycoprotein receptors-expressing HCC in vitro and in vivo. We evaluated the synergetic antitumor effect of miR-145 and CPT using CCK8, Western blotting, apoptosis and wound scratch assay in vitro, and the mechanisms underlying the synergetic antitumor effects were further investigated. Tumor inhibitory efficacy, safety evaluation and MRI-visible ability were assessed using diethylnitrosamine (DEN) + CCl 4 -induced HCC mouse model., Results: The LA modification improved the targeting delivery of cargos to HCC cells and tissues. The LA-CMGL-mediated co-delivery of miR-145 and CPT is more effective on tumor inhibitory than LA-CPT-L or LA-miR-145-L treatment alone, both in vitro and in vivo, with almost no side effects during the treatment period. Mechanistically, miR-145 likely induces apoptosis by targeting SUMO-specific peptidase 1 (SENP1)-mediated hexokinase (HK2) SUMOylation and glycolysis pathways and, in turn, sensitizing the cancer cells to CPT. In vitro and in vivo tests confirmed that the loaded Gd-DOTA served as an effective T1-weighted contrast agent for noninvasive tumor detection as well as real-time monitoring of drug delivery and biodistribution., Conclusions: The LA-CMGL-mediated co-delivery of miR-145 and CPT displays a synergistic therapy against HCC. The novel MRI-visible, actively targeted chemo-gene co-delivery system for HCC therapy provides a scientific basis and a useful idea for the development of HCC treatment strategies in the future., (© 2024. The Author(s).)

Background: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD., Methods: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk., Results: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk., Conclusion: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk., (© 2024. The Author(s).)

Background: The Correa's cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa's cascade are scarce., Methods: We compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979-2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison., Results: A total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08-1.14) for the normal mucosa group to 1.54 (95% CI 1.46-1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa's cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for "infectious diseases and parasitic diseases", "respiratory system diseases", and "digestive system disease", when using the normal mucosa group as reference., Conclusions: Increased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted., (© 2024. The Author(s).)

Background: Temperature fluctuations can impact the occurrence and progression of respiratory system diseases. However, the current understanding of the impact of temperature on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains limited. Therefore, our study aims to investigate the relationship between daily mean temperature (DMT) and the risk of AECOPD hospitalizations within Panzhihua City., Methods: We systematically collected data on AECOPD hospitalizations at Panzhihua Central Hospital from 2015 to 2020 and meteorological factors across Panzhihua City's districts. A two-stage analysis method was used to establish a distributed lag non-linear model to elucidate the influence of DMT on the frequency of admissions for AECOPD. Subgroup analyses were conducted by gender and age to identify populations potentially susceptible to the impact of DMT., Results: A total of 5299 AECOPD hospitalizations cases were included. The DMT and the risk of AECOPD hospitalization showed a non-linear exposure-response pattern, with low temperatures exacerbating the risk of hospitalizations. The lag effects of low temperature and relatively low temperature peaked at 2th day, with the lag effects disappearing at 16-17 days. Females and elders aged ≥ 65 years were more sensitive to effects of low and relatively low temperature at lag 0-4 days, while male AECOPD patients exhibited longer lasting lag effects., Conclusions: Low temperatures are associated with an increased risk of AECOPD hospitalizations. Females or elders aged ≥ 65 years with chronic obstructive pulmonary disease should pay more attention to taking protective measures in cold environments. These findings are crucial for the formulation of public health policies, as they will help significantly alleviate the burden of AECOPD and improve respiratory health in the face of climate challenges., (© 2024. The Author(s).)

Lewy body dementia (LBD), a class of disorders comprising Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), features substantial clinical and pathological overlap with Alzheimer's disease (AD). The identification of biomarkers unique to LBD pathophysiology could meaningfully advance its diagnosis, monitoring, and treatment. Using quantitative mass spectrometry (MS), we measured over 9,000 proteins across 138 dorsolateral prefrontal cortex (DLPFC) tissues from a University of Pennsylvania autopsy collection comprising control, Parkinson's disease (PD), PDD, and DLB diagnoses. We then analyzed co-expression network protein alterations in those with LBD, validated these disease signatures in two independent LBD datasets, and compared these findings to those observed in network analyses of AD cases. The LBD network revealed numerous groups or "modules" of co-expressed proteins significantly altered in PDD and DLB, representing synaptic, metabolic, and inflammatory pathophysiology. A comparison of validated LBD signatures to those of AD identified distinct differences between the two diseases. Notably, synuclein-associated presynaptic modules were elevated in LBD but decreased in AD relative to controls. We also found that glial-associated matrisome signatures consistently elevated in AD were more variably altered in LBD, ultimately stratifying those LBD cases with low versus high burdens of concurrent beta-amyloid deposition. In conclusion, unbiased network proteomic analysis revealed diverse pathophysiological changes in the LBD frontal cortex distinct from alterations in AD. These results highlight the LBD brain network proteome as a promising source of biomarkers that could enhance clinical recognition and management., (© 2024. The Author(s).)

Background: Acute exacerbation (AE) of interstitial lung disease (ILD) is one of the most serious complications during perioperative period of lung cancer resection. This study aimed to investigate the correlation between preoperative 2- deoxy-2-[18F]fluoro-D-glucose ( 18 F-FDG) PET/CT findings and AE in lung cancer patients with ILD., Methods: We retrospectively reviewed the data of 210 patients who underwent lung resection for non-small cell lung cancer. Relationships between clinical data and PET images and AE were evaluated. The patients were divided into an AE(+) and an AE(-) group for multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted and the area under curve (AUC) was used to assess the predictive values., Results: Among 210 patients, 48 (22.8%) were diagnosed with ILD based on chest CT. Among them, 9 patients (18.75%) developed AE after lung resection and were defined as AE(+) group. The course of ILD was longer in AE(+) group compared to AE(-) group. More patients in AE(+) group had a history of AE and chronic obstructive pulmonary disease (COPD) than in AE(-) group. The maximum standardized uptake value (SUVmax) of the noncancerous interstitial pneumonia (IP) area and cancers in AE(+) group was significantly higher compared to AE(-) group. Univariate logistic regression analysis showed that AE, COPD, SUVmax of the noncancerous IP area, SUVmax of cancer, surgical method were significantly correlated with AE. The course of ILD[OR(95%CI) 2.919; P = 0.032], SUVmax of the noncancerous IP area[OR(95%CI) 7.630;P = 0.012] and D-Dimer level[OR(95%CI) 38.39;P = 0.041] were identified as independent predictors for AE in patients with ILD after lung cancer surgery. When the three indicators were combined, we found significantly better predictive performance for postoperative AE than that of SUVmax of the noncancerous IP area alone [0.963 (95% CI 0.914-1.00); sensitivity, 100%, specificity 87.2%, P < 0.001 vs. 0.875 (95% CI 0.789 ~ 0.960); sensitivity, 88.9%, specificity, 76.9%, P = 0.001; difference in AUC = 0.088, Z = 1.987, P = 0.04]., Conclusion: The combination of the course of ILD, SUVmax of the noncancerous IP area and D-Dimer levels has high predictive value for the occurrence of AE in patients with concomitant interstitial lesions., (© 2024. The Author(s).)

Periodontitis is a chronic inflammatory disease characterized by plaque accumulation, resulting in immune microenvironment disorders and resorption of alveolar bone. To promote bone healing under inflammatory environments, a functional biomaterial based on disease pathophysiology is designed. A novel fatty acid C10-modified polypeptide, C 10 -KR8, is discovered to have excellent abilities in modulating macrophage repolarization and promoting bone regeneration in periodontitis. To build a multifunctional material localized drug delivery system, C 10 -KR8@ZIF-8 (C 10 -KR8-loaded zeolitic imidazolate framework-8) nanoparticles are constructed to sustainedly release the C 10 -KR8 peptide and Zn elements. By synergistic effects of providing a dynamic immuno-modulatory environment and promoting osteogenesis under pathological conditions, the obtained pH-responsive nanoparticles display excellent bone regeneration capability. Furthermore, coimmunoprecipitation/liquid chromatography-tandem mass spectrometry analysis and proteomics analysis revealed that the C 10 -KR8 peptide directly interacts with the high-temperature requirement protein A1 (Htra1), and C 10 -KR8@ZIF-8 nanoparticles promote the osteogenic differentiation of bone mesenchymal stem cells by activating the focal adhesion kinase (FAK)/phosphatidylinositide 3-kinase (PI3K)/AKT pathway and enhancing the nuclear localization of Yes-associated protein (YAP). Taken together, this study demonstrates C 10 -KR8 peptide regulate osteoimmunology and bone regeneration by Htra1/FAK/YAP pathway and that ZIF-8-based peptide loading platform is a promising strategy for periodontitis., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Xuechun Wang et al.)

Objectives: To systematically evaluate the therapeutic effect of electrical stimulation combined with pelvic floor muscle exercise on female pelvic floor dysfunction (PFD)., Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was applied. A computer-based retrieval was performed in the databases of PubMed, Web of Science, Embase, and Cochrane Library from database establishment to September 15, 2023, to identify randomized controlled trials on electrical stimulation combined with pelvic floor muscle function exercise on female PFD. Literature screening, data extraction, and quality evaluation were performed independently by two researchers, and meta-analysis was performed using the statistical software Stata15.0., Results: 1. In total, 12 randomized controlled trials were included, involving 721 female patients. The overall quality of methodologies employed in the included studies was relatively high. 2. Meta-analysis results showed that electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD (SMD = -1.01, 95% CI - 1.78, - 0.25, P < 0.05). 3. This combination treatment demonstrated a significant positive effect on the improvement of pelvic floor muscle strength in female patients (P < 0.05); however, it had no significant effect on the improvement in quality of life (P > 0.05)., Conclusions: Compared with pelvic floor muscle exercise alone, electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD. It had a notable positive impact on enhancing pelvic floor muscle strength in female patients, although it did not significantly improve quality of life. Future high-quality studies are warranted., (© 2024. The Author(s).)

The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM. Due to MM-assisted inflammation homing, intravenously injected NCs could efficiently accumulate at the fractured femur, where catalase decomposes the local hydrogen peroxide to generate oxygen bubbles that drives the shedding of sSDF-1α-anchored MM in the extracellular compartment. The exposed, cationic inner core thus enables robust trans-membrane delivery into MSCs to induce Ckip-1 silencing. Consequently, sSDF-1α-guided MSCs recruitment cooperates with siCkip-1-mediated osteogenic differentiation to facilitate bone formation and accelerate bone fracture healing. This study provides an enlightened strategy for the hierarchical co-delivery of macromolecular drugs into different cellular compartments, and it also renders a promising modality for the management of fracture healing., (© 2024. The Author(s).)

Background: Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic., Methods: A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6-13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023., Results: A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p < 0.001). The change in prevalence rate in myopia was shifted slightly in children aged 10-13 years. Children aged 8 to 13 years had a slight increase in myopia prevalence from 2022 to 2023. The prevalence of hyperopia was low and stable in all grade groups, ranging from 0.7% to 2.2% over five years., Conclusion: Myopia in children has increased rapidly during the COVID-19 pandemic. After the pandemic, the prevalence of myopia in children gradually decreased temporarily and then rebounded. Myopic shift was more apparent in younger children. Myopic shift in children may be related to the reduction of outdoor time, less light, and near work habits, and further research is needed., (© 2024. The Author(s).)

Objectives: Much has been written about the utility of genomic databases to public health. Within food safety these databases contain data from two types of isolates-those from patients (i.e., clinical) and those from non-clinical sources (e.g., a food manufacturing environment). A genetic match between isolates from these sources represents a signal of interest. We investigate the match rate within three large genomic databases (Listeria monocytogenes, Escherichia coli, and Salmonella) and the smaller Cronobacter database; the databases are part of the Pathogen Detection project at NCBI (National Center for Biotechnology Information)., Results: Currently, the match rate of clinical isolates to non-clinical isolates is 33% for L. monocytogenes, 46% for Salmonella, and 7% for E. coli. These match rates are associated with several database features including the diversity of the organism, the database size, and the proportion of non-clinical BioSamples. Modeling match rate via logistic regression showed relatively good performance. Our prediction model illustrates the importance of populating databases with non-clinical isolates to better identify a match for clinical samples. Such information should help public health officials prioritize surveillance strategies and show the critical need to populate fledgling databases (e.g., Cronobacter sakazakii)., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses., Results: We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC 50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10., Conclusions: Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED., (© 2024. The Author(s).)

Background: In knee osteoarthritis (KOA), treatments involving knee injections of bone marrow-derived mesenchymal stem cells (BM-MSC), adipose tissue-derived mesenchymal stem cells (AD-MSC), or umbilical cord-derived mesenchymal stem cells (UC-MSC) have shown promise in alleviating symptoms. However, which types of mesenchymal stem cells (MSCs) have the best therapeutic outcomes remain uncertain., Method: We systematically searched PubMed, OVID, Web of Science, and the Cochrane Library until January 1, 2024. The study evaluated five endpoints: Visual Analog Score (VAS) for Pain, Range of Motion (ROM), Whole-Organ Magnetic Resonance Imaging Score (WORMS), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and adverse events (ADs). Standard meta-analysis and network meta-analysis were performed using Stata 16.0., Results: Fifteen studies involving 585 patients were included in the meta-analysis. Standard meta-analysis revealed significant improvements with MSCs in VAS score (P < 0.001), knee ROM (P < 0.001), and WOMAC (P < 0.016) compared to traditional therapy. In the network meta-analysis, autologous MSCs significantly improved VAS score [SMD = 2.94, 95% CI (1.90, 4.56)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to traditional therapy. Similarly, BM-MSC significantly improved VAS score [SMD = 0.31, 95% CI (0.11, 0.91)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to hyaluronic acid. However, compared with traditional therapy, autologous or allogeneic MSCs were associated with more adverse reactions [SMD = 0.11, 95% CI (0.02, 0.59)], [SMD = 0.13, 95% CI (0.002, 0.72)]. Based on the surface under the cumulative ranking results, autologous BM-MSC showed the most improvement in ROM and pain relief in KOA patients, UC-MSC (SUCRA 94.1%) were most effective for positive WORMS, and AD-MSC (SUCRA 70.6%) were most effective for WOMAC-positive patients., Conclusion: MSCs transplantation effectively treats KOA patients, with autologous BM-MSC potentially offering more excellent benefits., (© 2024. The Author(s).)

Background: Mung bean (Vigna radiata L.) is an important warm-season grain legume. Adaptation to extreme environmental conditions, supported by evolution, makes mung bean a rich gene pool for stress tolerance traits. The exploration of resistance genes will provide important genetic resources and a theoretical basis for strengthening mung bean breeding. B-box (BBX) proteins play a major role in developmental processes and stress responses. However, the identification and analysis of the mung bean BBX gene family are still lacking., Results: In this study, 23 VrBBX genes were identified through comprehensive bioinformatics analysis and named based on their physical locations on chromosomes. All the VrBBXs were divided into five groups based on their phylogenetic relationships, the number of B-box they contained and whether there was an additional CONSTANS, CO-like and TOC1 (CCT) domain. Homology and collinearity analysis indicated that the BBX genes in mung bean and other species had undergone a relatively conservative evolution. Gene duplication analysis showed that only chromosomal segmental duplication contributed to the expansion of VrBBX genes and that most of the duplicated gene pairs experienced purifying selection pressure during evolution. Gene structure and motif analysis revealed that VrBBX genes clustered in the same group shared similar structural characteristics. An analysis of cis-acting elements indicated that elements related to stress and hormone responses were prevalent in the promoters of most VrBBXs. The RNA-seq data analysis and qRT-PCR of nine VrBBX genes demonstrated that VrBBX genes may play a role in response to environmental stress. Moreover, VrBBX5, VrBBX10 and VrBBX12 are important candidate genes for plant stress response., Conclusions: In this study, we systematically analyzed the genomic characteristics and expression patterns of the BBX gene family under ABA, PEG and NaCl treatments. The results will help us better understand the complexity of the BBX gene family and provide valuable information for future functional characteristics of specific genes in this family., (© 2024. The Author(s).)

Objective: To investigate whether the surgical process information sharing system could alleviate the parental anxiety during a pediatric selective operation., Design: Randomized controlled trial., Methods: A questionnaire survey was conducted one day before surgery for the enrolled participants. Family members assigned to the intervention group received real-time process information sharing through service reminders during the surgical period, while the control group received standard perioperative education. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality during the perioperative period, and the State of Cohesion-13 Scale (SOC-13) and Self-rating Anxiety Scale (SAS) were used to assess anxiety levels. Satisfaction levels during the perioperative period were assessed through a follow-up survey conducted one day after surgery., Results: The intervention group showed better scores in terms of PSQI, SOC-13, SAS, and postoperative satisfaction levels at various time points compared to the control group, with statistically significant differences observed (P < 0.05)., Conclusion: Real-time process information sharing is effective in reducing perioperative sleep disorders and anxiety among family members of pediatric patients, as well as improving satisfaction levels. This approach not only establishes a process and mechanism for effective doctor-patient communication but also helps implement continuous perioperative care, thereby optimizing internet healthcare services., (© 2024. The Author(s).)

Background: Machine learning (ML) has emerged as the predominant computational paradigm for analyzing large-scale datasets across diverse domains. The assessment of dataset quality stands as a pivotal precursor to the successful deployment of ML models. In this study, we introduce DREAMER (Data REAdiness for MachinE learning Research), an algorithmic framework leveraging supervised and unsupervised machine learning techniques to autonomously evaluate the suitability of tabular datasets for ML model development. DREAMER is openly accessible as a tool on GitHub and Docker, facilitating its adoption and further refinement within the research community.., Results: The proposed model in this study was applied to three distinct tabular datasets, resulting in notable enhancements in their quality with respect to readiness for ML tasks, as assessed through established data quality metrics. Our findings demonstrate the efficacy of the framework in substantially augmenting the original dataset quality, achieved through the elimination of extraneous features and rows. This refinement yielded improved accuracy across both supervised and unsupervised learning methodologies., Conclusion: Our software presents an automated framework for data readiness, aimed at enhancing the integrity of raw datasets to facilitate robust utilization within ML pipelines. Through our proposed framework, we streamline the original dataset, resulting in enhanced accuracy and efficiency within the associated ML algorithms., (© 2024. The Author(s).)

BACKGROUND ACMELLA RADICANS: (Jacquin) R.K. Jansen is a new invasive species record for Yunnan Province, China. Native to Central America, it has also been recently recorded invading other parts of Asia. To prevent this weed from becoming a serious issue, an assessment of its ecological impacts and potential distribution is needed. We predicted the potential distribution of A. radicans in China using the MaxEnt model and its ecological impacts on local plant communities and soil nutrients were explored. RESULTS: Simulated training using model parameters produced an area under curve value of 0.974, providing a high degree of confidence in model predictions. Environmental variables with the greatest predictive power were precipitation of wettest month, isothermality, topsoil TEB (total exchangeable bases), and precipitation seasonality, with a cumulative contribution of more than 72.70% and a cumulative permutation importance of more than 69.20%. The predicted potential suitable area of A. radicans in China is concentrated in the southern region. Projected areas of A. radicans ranked as high and moderately suitable comprised 5425 and 26,338 km 2 , accounting for 0.06 and 0.27% of the Chinese mainland area, respectively. Over the 5 years of monitoring, the population density of A. radicans increased while at the same time the population density and importance values of most other plant species declined markedly. Community species richness, diversity, and evenness values significantly declined. Soil organic matter, total N, total P, available N, and available P concentrations decreased significantly with increasing plant cover of A. radicans, whereas pH, total K and available K increased. CONCLUSION: Our study was the first to show that A. radicans is predicted to expand its range in China and may profoundly affect plant communities, species diversity, and the soil environment. Early warning and monitoring of A. radicans must be pursued with greater vigilance in southern China to prevent its further spread., (© 2024. The Author(s).)

Objective: Understanding the characteristics related to cardiorespiratory fitness after stroke can provide reference values for patients in clinical rehabilitation exercise. This meta- analysis aimed to investigate the effect of robot-assisted gait training in improving cardiorespiratory fitness in post-stroke patients, compared to conventional rehabilitation training., Methods: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, CBM, CNKI and Wanfang databases were searched until March 18th, 2024. Randomized controlled trials (RCTs) comparing the effectiveness of robot-assisted gait training versus control group were included. The main outcome variable was peak oxygen uptake. 6-minute walking test, peak heart rate, peak inspiratory expiratory ratio as our secondary indicators. RevMan 5.3 software was used for statistical analysis., Results: A total of 17 articles were included, involving 689 subjects. The results showed a significant effect for robot-assisted gait training to improve VO 2peak (MD = 1.85; 95% CI: -0.13 to 3.57; p = 0.04) and 6WMT (MD = 19.26; 95% CI: 10.43 to 28.08; p < 0.0001). However, no significant difference favouring robot-assisted gait training were found in HR peak (MD = 3.56; 95% CI: -1.90 to 9.02; p = 0.20) and RER peak (MD = -0.01; 95% CI: -0.04 to 0.01; p = 0.34)., Conclusion: These results showed that robot-assisted gait training may have a beneficial effect in improving VO 2peak and 6WMT, with a moderate recommendation level according to the GRADE guidelines., (© 2024. The Author(s).)

Background: Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems., Case Presentation: This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation., Conclusion: When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH., (© 2024. The Author(s).)

Background: Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives., Objectives: The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies., Design and Settings: A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021., Independent Variables: (a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors., Results: Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089)., Conclusion: Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings., (© 2024. The Author(s).)

Background: As the greenhouse effect intensifies, global temperatures are steadily increasing, posing a challenge to bread wheat (Triticum aestivum L.) production. It is imperative to comprehend the mechanism of high temperature tolerance in wheat and implement breeding programs to identify and develop heat-tolerant wheat germplasm and cultivars., Results: To identify quantitative trait loci (QTL) related to heat stress tolerance (HST) at seedling stage in wheat, a panel of 253 wheat accessions which were re-sequenced used to conduct genome-wide association studies (GWAS) using the factored spectrally transformed linear mixed models (FaST-LMM). For most accessions, the growth of seedlings was found to be inhibited under heat stress. Analysis of the phenotypic data revealed that under heat stress conditions, the main root length, total root length, and shoot length of seedlings decreased by 47.46%, 49.29%, and 15.19%, respectively, compared to those in normal conditions. However, 17 varieties were identified as heat stress tolerant germplasm. Through GWAS analysis, a total of 115 QTLs were detected under both heat stress and normal conditions. Furthermore, 15 stable QTL-clusters associated with heat response were identified. By combining gene expression, haplotype analysis, and gene annotation information within the physical intervals of the 15 QTL-clusters, two novel candidate genes, TraesCS4B03G0152700/TaWRKY74-B and TraesCS4B03G0501400/TaSnRK3.15-B, were responsive to temperature and identified as potential regulators of HST in wheat at the seedling stage., Conclusions: This study conducted a detailed genetic analysis and successfully identified two genes potentially associated with HST in wheat at the seedling stage, laying a foundation to further dissect the regulatory mechanism underlying HST in wheat under high temperature conditions. Our finding could serve as genomic landmarks for wheat breeding aimed at improving adaptation to heat stress in the face of climate change., (© 2024. The Author(s).)

Introduction: Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase., Materials and Methods: This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi'an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data., Results: Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 10 9 ), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 10 9 ). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration., Conclusion: Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain., (© 2024. The Author(s).)

Background: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs., Methods: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4) + T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells., Results: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4 + T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression., Conclusions: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) represents one of the deadliest cancers globally, making the search for more effective diagnostic and therapeutic approaches particularly crucial. Aptamer-functionalized nanomaterials (AFNs), an innovative nanotechnology, have paved new pathways for the targeted diagnosis and treatment of HCC. Initially, we outline the epidemiological background of HCC and the current therapeutic challenges. Subsequently, we explore in detail how AFNs enhance diagnostic and therapeutic efficiency and reduce side effects through the specific targeting of HCC cells and the optimization of drug delivery. Furthermore, we address the challenges faced by AFNs in clinical applications and future research directions, with a particular focus on enhancing their biocompatibility and assessing long-term effects. In summary, AFNs represent an avant-garde therapeutic approach, opening new avenues and possibilities for the diagnosis and treatment of HCC., (© 2024. The Author(s).)

Background: The onset of locomotive syndrome (LS) precedes that of frailty. Therefore, the first step in extending healthy life expectancy is to implement measures against LS in young adults. The aim of this study was to investigate the prevalence of LS and its associated factors in young adults for early detection and prevention of LS., Methods: The participants of this study comprised 413 university students specializing in health sciences (192 males and 221 females) with an average age of 19.1 ± 1.2 years. All participants voluntarily participated in the study and reported no serious health problems. The presence or absence of LS was evaluated using the stand-up test, two-step test, and the 25-question Geriatric Locomotive Function Scale. Additionally, musculoskeletal assessment (one-leg standing, squatting, shoulder elevation, and standing forward bend), body composition analysis (weight, body mass index, body fat mass, body fat percentage, skeletal muscle mass index (SMI), and phase angle), handgrip strength test, physical activity assessment, and nutritional assessment were conducted. Sex-stratified analyses were performed, comparing groups with and without LS. Factors associated with LS were explored using binomial logistic regression., Results: Of the 413 young adults studied, 86 individuals (20.8%) were found to have LS. When stratified by sex, LS was observed to have a considerably higher prevalence in females (55, 24.9%) than in males (31, 16.1%). In males, the notable differences between the groups with and without LS were observed in one-leg standing and phase angle, whereas in females, differences were identified in body fat mass, body fat percentage, SMI, musculoskeletal pain, and handgrip strength. Two types of binomial logistic regression analysis revealed that the inability to perform one-leg standing was associated with LS in males, while the presence of musculoskeletal pain and a high body fat percentage were identified as factors associated with LS in females., Conclusions: One in five young adults were found to have LS in this study, underscoring the necessity for early intervention and LS health education. Furthermore, effective management of musculoskeletal pain is also crucial., (© 2024. The Author(s).)

Background: Coccidiosis is one of the most frequently reported diseases in chickens, causing a significant economic impact on the poultry industry. However, there have been no previous studies evaluating the prevalence of this disease in broiler farms in Guangdong province. Therefore, this study aims to conduct an epidemiological investigation into the occurrence of Eimeria species and associated risk factors in intensive management conditions across four regions in Guangdong province, China. A total of 394 fecal samples were collected from 89 broiler farms in Guangdong province. The prevalence of Eimeria species infection was determined using PCR, and the occurrence of Clostridium perfringens type A was assessed using quantitative real-time PCR., Results: The results showed an overall prevalence of 98.88% (88/89) at the farm level and 87.06% (343/394) at the flock level. All seven Eimeria species were identified, with E. acervulina (72.53%; 64/89), E. tenella (68.54%; 61/89), and E. mitis (66.29%; 59/89) at the farm level, and E. acervulina (36.55%; 144/394), E. mitis (35.28%; 139/394), and E. tenella (34.01%; 134/394) at the flock level. The predominant species combination observed was a co-infection of all seven Eimeria species (6.74%; 6/89), followed by a combination of E. acervulina, E. tenella, E. mitis, E. necatrix, E. brunetti, and E. maxima (5.62%, 5/89). A combination of E. acervulina, E. tenella, E. mitis, E. necatrix, E. brunetti, and E. praecox (4.49%; 4/89) was also observed at the farm level. Furthermore, the study identified several potential risk factors associated with the prevalence of Eimeria species, including farm location, chicken age, drinking water source, control strategy, and the presence of C. perfringens type A were identified as potential risk factors associated with prevalence of Eimeria species. Univariate and multivariate analyses revealed a significant association between E. necatrix infection and both grower chickens (OR = 10.86; 95% CI: 1.92-61.36; p < 0.05) and adult chickens (OR = 24.97; 95% CI: 4.29-145.15; p < 0.001) compared to starter chickens at the farm level. Additionally, farms that used groundwater (OR = 0.27; 95% CI: 0.08-0.94; p < 0.05) were less likely to have E. maxima compared to those that used running water. At the flock level, the prevalence of E. tenella was significantly higher in the Pearl River Delta (OR = 2.48; 95% CI: 1.0-6.15; p = 0.05) compared to eastern Guangdong. Interestingly, flocks with indigenous birds were less likely to have E. brunetti (OR = 0.48; 95% CI: 0.26-0.89; p < 0.05) compared to flocks with indigenous crossbred birds. Furthermore, flocks that used anticoccidial drugs (OR = 0.09; 95% CI: 0.03-0.31; p < 0.001) or a combination of vaccines and anticoccidial drugs (OR = 0.06; 95% CI: 0.01-0.25; p < 0.001) were less likely to be positive for E. tenella compared to flocks that only used vaccines. Finally, flocks with C. perfringens type A infection were significantly more likely to have E. necatrix (OR = 3.26; 95% CI: 1.96-5.43; p < 0.001), E. tenella (OR = 2.14; 95% CI: 1.36-3.36; p < 0.001), E. brunetti (OR = 2.48; 95% CI: 1.45-4.23; p < 0.001), and E. acervulina (OR = 2.62; 95% CI: 1.69-4.06; p < 0.001) compared to flocks without C. perfringens type A., Conclusions: This study conducted an investigation on the prevalence, distribution, and risk factors associated with Eimeria species infection in broiler chickens in Guangdong. The farm-level prevalence of Eimeria species was higher than the previous prevalence figures for other areas and countries. E. brunetti was identified at higher prevalence in Guangdong than previously survived prevalence in different regions in China. Farm location, chicken age, drinking water source, control strategy, and the presence of C. perfringens type A were considered as potential risk factors associated with prevalence of Eimeria species. It is imperative to underscore the necessity for further surveys to delve deeper into the occurrence of Eimeria species under intensive management conditions for different flock purposes., (© 2024. The Author(s).)

Background: Endometria are one of the important components of the uterus, which is located in the peritoneal cavity. Endometrial injury usually leads to intrauterine adhesions (IUA), accompanied by inflammation and cell death. We previously reported that both the endometrial ferroptosis was increased and monocytes/macrophages were involved in endometrial injury of IUA. Large peritoneal macrophages (LPMs) are recently reported to migrate into the injured tissues and phagocytose dead cells to repair the tissues. We previously demonstrated that mesenchymal stromal cells (MSCs) had made excellent progress in the repair of endometrial injury. However, it is unclear whether MSCs regulate the LPM efferocytosis against ferroptotic monocytes/macrophages in the injured endometria., Methods: Here, endometrial injury in IUA mouse model was conducted by uterine curettage and LPS injection surgery and the samples were collected at different times to detect the changes of LPMs and ferroptotic monocytes/macrophages. We conducted LPMs depletion assay in vivo and LPMs and Erastin-induced ferroptotic THP-1 cells coculture systems in vitro to detect the LPM efferocytosis against ferroptotic monocytes/macrophages. The IUA model was treated with MSCs, and their effects on LPMs and endometrial repair were analyzed. Flow cytometry, western blotting, quantitative real-time PCR, immunohistochemical analysis, ELISA, and RNA-sequencing were performed., Results: We found that LPMs migrated to the injured uteri in response to the damage in early phase (3 h), and sustained to a later stage (7 days). Astonishingly, we found that ferroptotic monocytes/macrophages were significantly increased in the injured uteri since 12 h after injury. Moreover, LPMs cocultured with Erastin-induced ferroptotic THP-1 cells in vitro, efferocytosis of LPMs against ferroptotic monocytes/macrophages was emerged. The mRNA expression profiles revealed that LPM efferocytosis against ferroptotic monocytes/macrophages was an induction of glycolysis program and depended on the PPARγ-HK2 pathway. Importantly, we validated that MSCs promoted the efferocytic capability and migration of LPMs to the injured uteri via secreting stanniocalcin-1 (STC-1)., Conclusion: The data collectively demonstrated first the roles of LPMs via removal of ferroptotic monocytes/macrophages and provided a novel mechanism of MSCs in repairing the endometrial injury., (© 2024. The Author(s).)

Background: Osteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear., Methods: In this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1β) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1β-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays., Results: Downregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway., Conclusions: This study demonstrated that CHMP5 repressed IL-1β-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future., (© 2024. The Author(s).)

Objective: To assess the prevalence of anemia among pregnant women across their entire pregnancy and the factors affecting it in the monitoring areas., Methods: A total of 108,351 pregnant women who received antenatal health care and delivered from January 1, 2016 to December 31, 2020 in 15 monitoring counties of 8 provinces in the Maternal and Newborn Health Monitoring Program (MNHMP) of National Center for Women and Children's Health (NCWCH) were selected as the study subjects. The anemia status among the subjects across their first, second and third trimester of pregnancy and the influencing factors were analyzed., Results: From 2016 to 2020, the prevalence of anemia at any stage during pregnancy in the monitoring areas was 43.59%. The prevalence of anemia among pregnant women across all three trimesters was 3.95%, and the prevalence of mild and moderate-to-severe anemia was 1.04% and 2.90%, respectively. Protective factors were living in the northern area (OR = 0.395) and being a member of an ethnic minority (OR = 0.632). The risk factors were residing in rural areas (OR = 1.207), with no more than junior high school education (OR = 1.203), having ≥ 3 gravidities (OR = 1.195) and multiple fetuses (OR = 1.478)., Conclusions: Although the prevalence of anemia among pregnant women across all trimesters in the monitoring area was low, the severity of anemia was high. Since the prevalence of anemia among pregnant women across their entire pregnancy in the monitoring area is affected by many different factors, more attention should be paid to pregnant women living in rural areas, with low literacy, ≥ 3 gravidities and multiple fetuses for early intervention., (© 2024. The Author(s).)