SUN5 interacts with nuclear membrane LaminB1 and cytoskeletal GTPase Septin12 mediating the sperm head-and-tail junction.

Acephalic spermatozoa syndrome (ASS) is a severe teratospermia with decaudated, decapitated, and malformed sperm, resulting in male infertility. Nuclear envelope protein SUN5 localizes to the junction between the sperm head and tail. Mutations in the SUN5 gene have been identified most frequently (33-47%) in ASS cases, and its molecular mechanism of action is yet to be explored. In the present study, we generated Sun5 knockout mice, which presented the phenotype of ASS. Nuclear membrane protein LaminB1 and cytoskeletal GTPases Septin12 and Septin2 were identified as potential partners for interacting with SUN5 by immunoprecipitation-mass spectrometry in mouse testis. Further studies demonstrated that SUN5 connected the nucleus by interacting with LaminB1 and connected the proximal centriole by interacting with Septin12. The binding between SUN5 and Septin12 promoted their aggregation together in the sperm neck. The disruption of the LaminB1/SUN5/Septin12 complex by Sun5 deficiency caused separation of the Septin12-proximal centriole from the nucleus, leading to the breakage of the head-to-tail junction. Collectively, these data provide new insights into the pathogenesis of ASS caused by SUN5 deficiency.

The impact of squamous cell transformation on the prognosis of patients treated with radical nephroureterectomy.

BACKGROUND: Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy. METHODS: We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses. RESULTS: The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS. CONCLUSIONS: SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.

The prevalence and genotype distribution of human papillomavirus in central Fujian Province during the COVID-19 pandemic.

BACKGROUND: Global human activities were significantly impacted by the emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by the 2019 novel coronavirus. This study aimed to investigate the prevalence and genotype distribution of HPV infection in Central Fujian Province during the pandemic. METHODS: Cervical samples were collected from 21,612 outpatients and 12,664 females who underwent physical examinations and HPV screening at the People's Hospital of Fujian Province in Fuzhou from April 2020 to April 2023. HPV detection and genotyping were conducted using PCR hybridization. RESULTS: The overall HPV infection rate was 16.1% during the COVID-19 pandemic, with the outpatient group exhibiting a greater infection rate (19.0%) than did the healthy group (12.3%). The top five high-risk HPV (HR-HPV) genotypes in both groups were HPV52, HPV53, HPV58, HPV16, and HPV51. Additionally, HPV81 and HPV43 were the two most common low-risk HPV (LR-HPV) genotypes in the patient group, while HPV81 and HPV42 were the two most common LR-HPV genotypes in the healthy group. The highest prevalence of HPV infection was observed in individuals aged ≤ 24 years (28.4%, 95% CI 25.9-30.9), followed by those aged ≥ 55 years (23.6%, 95% CI 21.6-24.7) and other age groups. The prevalence decreased from 23.0% (95% CI 22.4-23.7) in 2018-2019 to 13.8% (95% CI 12.0-15.5) in 2023. CONCLUSION: This study provides valuable insights into the prevalence and genotypes of HPV infection in the female population of Central Fujian Province from 2020 to 2023. The findings indicate that the prevalence of HPV infection in Central Fujian Province remains relatively low compared to the national average. Furthermore, the prevalence of HPV decreased during the COVID-19 pandemic; however, as the pandemic waned, there was potential for an increase in HPV infection rates. Therefore, it is crucial to strengthen HPV screening and vaccination strategies to prevent the potential spread of HPV.

Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children.

OBJECTIVE: To investigate the association between loci rs3761847 and rs10818488 of tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) gene and the susceptibility to IgAV. METHODS: 100 blood samples of children with IgAV and 100 blood samples of healthy children were collected from the Third Xiangya Hospital of Central South University from June 2017 to June 2019. The target gene fragment was amplified by polymerase chain reaction (PCR), and the single nucleic acid gene polymorphism of the gene loci was detected by PCR sequencing based typing technique. The association between gene polymorphism of each locus and susceptibility to IgAV was analyzed. RESULTS: There were significant differences in both genotype (P < .05) and allele frequencies （P < .05) of rs3761847 of TRAF1/C5 gene between the IgAV group and the control group.Besides, the risks of developing IgAV in children with the TT genotype was 0.495 times and in children with the C allele was 1.627 times of that in children with other genotypes and alleles, respectively (P < .05). For IgAV patients, renal involvement risk in children with CC genotype was 5.859 times of that in children with other genotypes (P < .05). There were no significant differences in genotype (P > .05) and allele frequencies (P > .05) of rs10818488 of TRAF1/C5 gene between the IgAV group and the control group. IgAV patients with TT genotype had a 3.2 times higher risk of renal involvement than those with other genotypes (P < .05). CONCLUSIONS: There is an association between locus rs3761847 of TRAF1/C5 gene single nucleotide polymorphisms and susceptibility to IgAV. The T allele at locus rs3761847 of TRAF1/C5 gene may be a protective factor for IgAV. The C allele at locus rs3761847 and the T allele at locus rs10818488 of TRAF1/C5 gene may be associated with kidney injury in IgAV.

Novel Compound Heterogeneous Mutations in CYB5R3 Gene Leading to Methemoglobinemia (Type I) in a Chinese Boy: Case Report and Relevant Comprehensive Analysis.

INTRODUCTION: Recessive congenital methemoglobinemia (RCM) caused by CYB5R3 deficiency due to the mutations in the reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase (CYB5R) gene is an autosomal recessive inherited disease. Clinically, it can be divided into two types, namely red blood cell affected type (RCM I) and systemically affected type (RCM II). CASE PRESENTATION: A 5-year-old male patient was diagnosed with cyanosis for 5 years. Physical examination showed cyanosis in areas such as the lips, fingers, and toes. Laboratory examination revealed low pulse oxygen saturation (81%) and increased blood methemoglobin (23.6%). Gene testing revealed the compound heterozygous mutations in the CYB5R3 gene, c.149G>A (p.Arg50Gln) and c.331A>G (p.Lys111Glu), respectively originating from his parents. By constructing 3D models of CYB5R3 wild-type and mutant types using SWISS-MODEL software, it was found that the mutation caused significant structural abnormalities in the CYB5R protein. The relationship between CYB5R3 gene mutation sites, amino acid change, enzyme activity, and methemoglobinemia type I and II were listed and analyzed. CONCLUSION: A case of congenital RCM type I caused by compound heterozygous mutations in the CYB5R3 gene was reported, with c.331A>G (p.Lys111Glu) being the newly reported mutation. The homozygosity or heterozygosity of CYB5R3 gene mutations that lead to premature termination, loss of exons, and change in amino acid properties in FAD or NADH binding domains, is positively correlated with the severity (from type I to type II) of methemoglobinemia.

Reliability and validity of the Chinese version of the coronary artery disease empowerment scale (CADES) in patients with coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Empowerment is a comprehensive concept involving intrapersonal, interactional, and behavioral aspects. However, there is a lack of a specific empowerment scale for Coronary artery disease (CAD) related to knowledge and skills in China. The reliability and validity of the Coronary Artery Disease Empowerment Scale (CADES) need to be tested. This study aimed to assess the reliability and validity of the Chinese version of CADES among patients with CAD in China. METHODS: The study adopted a cross-sectional design. After obtaining the copyright by contacting the author, the original English CADES was developed into Chinese by forward translation, back-translation, cross-cultural adaptation, and a pretest (30 patients). The Chinese version of CADES was administered to 391 CAD patients between September 2022 and June 2023, with the reliability and validity of the version evaluated. Exploratory factor analysis and confirmatory factor analysis were performed to examine the underlying factor structure of the translated questionnaire. The Cronbach's α coefficient, Guttman's split-half coefficient, and McDonald's omega coefficient were calculated to verify the scale's reliability. RESULTS: For the Chinese version of CADES, the scale-content validity index was 0.972, with the item-content validity index ranging from 0.86 to 1.00. The questionnaire comprised 25 items, and exploratory factor analysis extracted four factors with loadings > 0.40, explaining 62.382% of the total variance. An acceptable model fit was achieved (χ2/df = 1.764, RMSEA = 0.060, TLI = 0.901, CFI = 0.912, IFI = 0.913). The Cronbach's α coefficient of the total questionnaire was 0.928, with coefficients for the four factors ranging from 0.683 to 0.913. The split-half reliability coefficient was 0.777, and the McDonald's omega reliability coefficient was 0.926. CONCLUSIONS: The Chinese version of CADES is reliable and valid among CAD patients in China. This instrument can serve as a valuable reference for guiding the implementation of targeted intervention strategies tailored to the empowerment status of CAD patients in clinical practice.

Comparative analysis of testicular fusion in Spodoptera litura (cutworm) and Bombyx mori (silkworm): Histological and transcriptomic insights.

Spodoptera litura commonly known as the cutworm, is among the most destructive lepidopteran pests affecting over 120 plants species. The powerful destructive nature of this lepidopteran is attributable to its high reproductive capacity. The testicular fusion that occurs during metamorphosis from larvae to pupa in S.litura positively influences the reproductive success of the offspring. In contrast, Bombyx mori, the silkworm, retains separate testes throughout its life and does not undergo this fusion process. Microscopic examination reveals that during testicular fusion in S.litura, the peritoneal sheath becomes thinner and more translucent, whereas in B.mori, the analogous region thickens. The outer basement membrane in S.litura exhibits fractures, discontinuity, and uneven thickness accompanied by a significant presence of cellular secretions, large cell size, increased vesicles, liquid droplets, and a proliferation of rough endoplasmic reticulum and mitochondria. In contrast, the testicular peritoneal sheath of B.mori at comparable developmental stage exhibits minimal change. Comparative transcriptomic analysis of the testicular peritoneal sheath reveals a substantial difference in gene expression between the two species. The disparity in differential expressed genes (DEGs) is linked to an enrichment of numerous transcription factors, intracellular signaling pathways involving Ca2+ and GTPase, as well as intracellular protein transport and signaling pathways. Meanwhile, structural proteins including actin, chitin-binding proteins, membrane protein fractions, cell adhesion, extracellular matrix proteins are predominantly identified. Moreover, the study highlights the enrichment of endopeptidases, serine proteases, proteolytic enzymes and matrix metalloproteins, which may play a role in the degradation of the outer membrane. Five transcription factors-Slforkhead, Slproline, Slcyclic, Slsilk, and SlD-ETS were identified, and their expression pattern were confirmed by qRT-PCR. they are candidates for participating in the regulation of testicular fusion. Our findings underscore significant morphological and trancriptomic variation in the testicular peritoneal sheath of S.litura compared to the silkworm, with substantial changes at the transcriptomic level coinciding with testicular fusion. The research provides valuable clues for understanding the complex mechanisms underlying this unique phenomenon in insects.

Comparison of 19G FNA Versus 22G FNB Needles for Endoscopic Ultrasound-Guided Fine-Needle Sampling of Subepithelial Tumors: Is Bigger Better?

OBJECTIVES: To compare the diagnostic efficiency of 19G fine-needle aspiration (FNA) and 22G fine-needle biopsy (FNB) in endoscopic ultrasound (EUS)-guided sampling for subepithelial tumors (SETs). METHODS: The data of patients with SETs who underwent 19G FNA or 22G FNB were reviewed retrospectively in two tertiary hospitals. Tissue cores were assessed by macroscopic on-site evaluation (MOSE). Cytological or histological diagnosis were classified as definite, suspect, or no diagnosis. RESULTS: Seventy five patients (mean age: 55 years, 44 males) underwent 19G EUS-FNA (31) or 22G EUS-FNB (44). The overall diagnostic yield was 82.7%. The rate of definite cytological diagnoses was 9.7% (3/31) in 19G and 13.6% (6/44) in 22G group (x2 = 1.520, P = .468). In terms of MOSE, 19G needle, requiring only two punctures, achieved a higher good tissue core rate than 22G group (100.0% [31/31] versus 84.1% [37/44], x2 = 5.440, P = .020]). For histological diagnosis, the 19G group achieved higher definite rate than the 22G group, 93.6% (29/31) versus 65.9% (29/44) (x2 = 7.957, P = .019) on the first puncture, 90.3% (28/31) versus 63.6% (28/44) (x2 = 7.139, P = .028) on the second puncture, 96.8% (30/31) versus 70.5% (31/44) (x2 = 7.319, P = .026) on both the first and second punctures, and 96.8% (30/31) versus 72.7% (32/44) (x2 = 7.538, P = .023) on all three punctures. CONCLUSIONS: The 19G EUS-FNA requires only two punctures to achieve better tissue core quality by MOSE and yields a higher rate of histological diagnosis than 22G ProCore needle for SETs. The bigger 19G FNA needle seems to play an important role in the evaluation of SETs.

SUN5, a testis-specific nuclear membrane protein, participates in recruitment and export of nuclear mRNA in spermatogenesis.

SUN5, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that Sun5 is involved in mRNA export. In Sun5-knockout mice ( Sun5 -/-), poly(A) + RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of Sun5, heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A) + RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that Sun5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that Sun5 regulates mRNA export through an Nxf1-dependent pathway. In Sun5 -/- mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.

Embodied Conversational Agents for Chronic Diseases: Scoping Review.

BACKGROUND: Embodied conversational agents (ECAs) are computer-generated animated humanlike characters that interact with users through verbal and nonverbal behavioral cues. They are increasingly used in a range of fields, including health care. OBJECTIVE: This scoping review aims to identify the current practice in the development and evaluation of ECAs for chronic diseases. METHODS: We applied a methodological framework in this review. A total of 6 databases (ie, PubMed, Embase, CINAHL, ACM Digital Library, IEEE Xplore Digital Library, and Web of Science) were searched using a combination of terms related to ECAs and health in October 2023. Two independent reviewers selected the studies and extracted the data. This review followed the PRISMA-ScR (Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. RESULTS: The literature search found 6332 papers, of which 36 (0.57%) met the inclusion criteria. Among the 36 studies, 27 (75%) originated from the United States, and 28 (78%) were published from 2020 onward. The reported ECAs covered a wide range of chronic diseases, with a focus on cancers, atrial fibrillation, and type 2 diabetes, primarily to promote screening and self-management. Most ECAs were depicted as middle-aged women based on screenshots and communicated with users through voice and nonverbal behavior. The most frequently reported evaluation outcomes were acceptability and effectiveness. CONCLUSIONS: This scoping review provides valuable insights for technology developers and health care professionals regarding the development and implementation of ECAs. It emphasizes the importance of technological advances in the embodiment, personalized strategy, and communication modality and requires in-depth knowledge of user preferences regarding appearance, animation, and intervention content. Future studies should incorporate measures of cost, efficiency, and productivity to provide a comprehensive evaluation of the benefits of using ECAs in health care.

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives.

Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/ß-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.

Development and implementation of evidence-based, nurse-leading early warning model and healthcare quality improvement project for transplant-associated thrombotic microangiopathy: a mixed-methods, before-and-after study.

OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.

Effectiveness of Implementing Modified Early Warning System and Rapid Response Team for General Ward Inpatients.

This retrospective study assessed the effectiveness and impact of implementing a Modified Early Warning System (MEWS) and Rapid Response Team (RRT) for inpatients admitted to the general ward (GW) of a medical center. This study included all inpatients who stayed in GWs from Jan. 2017 to Feb. 2022. We divided inpatients into GWnon-MEWS and GWMEWS groups according to MEWS and RRT implementation in Aug. 2019. The primary outcome, unexpected deterioration, was defined by unplanned admission to intensive care units. We defined the detection performance and effectiveness of MEWS according to if a warning occurred within 24 h before the unplanned ICU admission. There were 129,039 inpatients included in this study, comprising 58,106 GWnon-MEWS and 71,023 GWMEWS. The numbers of inpatients who underwent an unplanned ICU admission in GWnon-MEWS and GWMEWS were 488 (.84%) and 468 (.66%), respectively, indicating that the implementation significantly reduced unexpected deterioration (p < .0001). Besides, 1,551,525 times MEWS assessments were executed for the GWMEWS. The sensitivity, specificity, positive predicted value, and negative predicted value of the MEWS were 29.9%, 98.7%, 7.09%, and 99.76%, respectively. A total of 1,568 warning signs accurately occurred within the 24 h before an unplanned ICU admission. Among them, 428 (27.3%) met the criteria for automatically calling RRT, and 1,140 signs necessitated the nursing staff to decide if they needed to call RRT. Implementing MEWS and RRT increases nursing staff's monitoring and interventions and reduces unplanned ICU admissions.

The effect of cognition in combination with an ACBT on dyspnea-related kinesiophobia in patients with moderate to severe COPD: Quasirandomized controlled trial study.

Patients with moderate to severe COPD frequently experience dyspnea, which causes these patients to acquire a fear of dyspnea and a fear of activity. This study developed a cognitive intervention combined with active cycle of breathing technique (ACBT) intervention program based on the fear-avoidance model, with the goal of evaluating the program's effectiveness in improving dyspnea-related kinesiophobia in patients with moderate to severe COPD. This study had a total of 106 participants. For 8 weeks, the intervention group (N=53) received cognitive combined with ACBT, while the control group (N=53) received standard care. The findings of the four times the dyspnea belief questionnaire were collected indicated that the combined intervention had a better impact on reducing dyspnea-related kinesiophobia than did routine nursing (P<0.05), and the impact persisted even after the intervention. Additionally, it may enhance dyspnea and quality of life, increase exercise capacity, and lower the BODE index.

[Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury].

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.

New prediction equations for knee isokinetic strength in young and middle-aged non-athletes.

BACKGROUND: This study aimed to develop alternative prediction equations to predict isokinetic muscle strength at 60°/s based on anthropometric characteristics, including body mass, height, age, and sex for young and middle-aged non-athlete populations. METHODS: Three hundred and thirty-two healthy non-athletic participants (174 females, 158 males) between 20 and 59 years underwent a 60°/s isokinetic knee joint concentric contraction test. Forty people were randomly selected for retesting to assess the reliability of the isokinetic instrument. Multivariate linear regression was used to establish extension peak torque (EPT) and flexion peak torque (FPT) prediction equations. Sixty extra participants were used individually to validate the prediction equations, and Bland Altman plots were constructed to assess the agreement of predicted values with actual measurements. RESULTS: The result demonstrated that the instrument we used has excellent reliability. The multivariable linear regression model showed that body mass, age, and sex were significant predictors of PT (EPT: Adjusted R2 = 0.804, p < 0.001; FPT: Adjusted R2 = 0.705, p < 0.001). Furthermore, the equations we established had higher prediction accuracy than those of Gross et al. and Harbo et al. CONCLUSION: The equations developed in this study provided relatively low bias, thus providing a more suitable reference value for the knee isokinetic strength of young and middle-aged non-athletes.

A study on the visual recognition patterns of multi-information guide signs based on eye movement data analysis.

A two-factor experiment was devised to assess the appropriateness of the quantity and arrangement of information on multi-information guide signs at unique, spacious exits on elevated expressway sections. This experiment investigated 77 signs containing varying amounts of road name information and different placements of destination road names. The research entailed an indoor experiment that incorporated eye-tracking technology and involved the analysis of a total of twenty-eight indicators. A comprehensive index system was developed, identifying three key aspects: visual recognition efficiency, visual recognition difficulty, and visual fatigue. Utilizing repeated measure analysis of variances, the impact of these two factors was examined to identify significant indicators and establish a comprehensive assessment indicator system. The Technique for Order of Preference by Similarity to Ideal Solution method, in conjunction with the coefficient of entropy weight, was employed to assess the effectiveness of these two factors. The findings demonstrated that the 28 eye-movement indicators utilized in this study effectively constitute a valuable indicator system for evaluating drivers' visual recognition characteristics. These indicators capture the subtle psychophysical traits inherent in the process of recognizing signs, including visual recognition efficiency, difficulty, and fatigue. Regarding the first experimental factor, the number of sign road names significantly influences drivers' visual recognition characteristics (Sig < 0.05). Specifically, an increase in the number of sign road names leads to diminished visual recognition efficiency and heightened visual recognition difficulty and fatigue. Consequently, it is advisable to restrict the number of sign road names to a maximum of six per sign under typical circumstances, with nine being the limit under special conditions. As for the second experimental factor, the placement of the destination road name within the sign layout exerts a significant impact on visual recognition characteristics (Sig < 0.05). Each type of multi-information sign exhibits a distinct visual recognition pattern. Generally, the upper portion of the sign is more easily recognized, while the lower part poses greater recognition challenges. Therefore, to mitigate visual recognition risks, it is recommended that road information placement be prioritized based on actual usage conditions.

Toxic Effects of Rare Earth Elements on Human Health: A Review.

Rare earth elements (REEs) are a new type of material resource which have attracted significant attention in recent years. REEs have emerged as essential metals in modern-day technology due to their unique functions. The long-term, large-scale mining and utilization of rare earths has caused serious environmental pollution and constitutes a global health issue, which has raised concerns regarding the safety of human health. However, the toxicity profile of suspended particulate matter in REEs in the environment, which interacts with the human body, remains largely unknown. Studies have shown that REEs can enter the human body through a variety of pathways, leading to a variety of organ and system dysfunctions through changes in genetics, epigenetics, and signaling pathways. Through an extensive literature search and critical analysis, we provide a comprehensive overview of the available evidence, identify knowledge gaps, and make recommendations for future research directions.

Higher Order Structure Characterization of Two Interdomain Disulfide Bond Variants of a Bispecific Monoclonal Antibody.

Characterization and understanding of protein higher order structure (HOS) is essential at all stages of biologics development. Here, two folding variants of a bispecific monoclonal antibody, the correctly folded form and an alternative configuration with reduced potency, were characterized by several HOS characterization techniques. Specifically, differential scanning calorimetry (DSC), circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), Raman and Raman optical activity (ROA) spectroscopy were used together to elucidate the impacts of disulfide bond scrambling in the fused scFv domains on the structure and thermal stability of the antibody. This study illustrates the importance of selecting appropriate biophysical characterization techniques based on the nature and magnitude of the HOS change.

WTAP-mediated abnormal m6A modification promotes cancer progression by remodeling the tumor microenvironment: bibliometric and database analyses.

Background: Wilms' tumor 1 associated protein (WTAP) is an essential component of the m6A methyltransferase complex. The research on WTAP has been continuously developed and promoted in recent years. It is needed to make systematic specific bibliometric and database analyses on WTAP, to identify the cooperation and impact of authors, countries, institutions and journals, to evaluate the knowledge base and find the hotspot trends, and to detect the emerging topics regarding WTAP research. Methods: The related articles and reviews of WTAP in the Web of Science Core Collection from January 1999 to June 2022 were retrieved, and CiteSpace and VOSviewer were used to perform bibliometric and knowledge-map analyses. Multiple databases were used to explore the expression level of WTAP in pan-cancers and its correlation with prognosis and immune infiltration. Results: In recent years, the number of publications on WTAP research has increased rapidly. Among the journals publishing WTAP research, Frontiers in Cell and Developmental Biology had the most papers, while Nature papers were most cited. The country with the highest number of publications on WTAP was China, and China Medical University was the institution with the most publications. The most prominent author was Haruo Sugiyama from Japan. Four main aspects of WTAP research included m6A modification, tumor association, cancer therapy, and regulatory mechanisms. The research frontiers and hotspots were m6A modification, methyltransferase, demethylation, tumor microenvironment (TME), and immunotherapy. Bioinformatics analysis showed that the expression of WTAP was up-regulated in a variety of tumors and closely related to TME and survival prognosis. Conclusions: From the bibliometric and database analyses on the researches on WTAP, it is suggested that up-regulated WTAP in cancers may promote cancer progression by mediating abnormal m6A modifications to reshape the TME, thereby affecting the survival prognosis of the patients. The information would provide helpful references for scholars focusing on WTAP and provide new insights for WTAP as a prognostic evaluation and immunotherapy for tumors in the future.