Atypical behaviour and connectivity in SHANK3-mutant macaques.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.

GRP78 promotes bone metastasis of prostate cancer by regulating bone microenvironment through Sonic hedgehog signaling.

Bone metastasis is the leading cause of tumor-related deaths in patients with prostate cancer (PCa). The interactions between PCa and the bone microenvironment form a vicious cycle. However, the complex molecular mechanism by which PCa regulates the bone microenvironment remains unclear. To determine the role of glucose-regulated protein (GRP78) in bone metastasis and growth, we established intracardiac injection and tibial injection models, and performed their histological staining. To assess the effect of GRP78 on the differentiation of osteoblasts and osteoclasts, we performed cell co-culture, enzyme-linked immunosorbent assay, alizarin red staining, and tartrate-resistant acid phosphatase staining. We found that GRP78 is upregulated in PCa tissues and that its upregulation is associated with PCa progression in patients. Functional experiments showed that GRP78 overexpression in PCa cells considerably promotes bone metastasis and induces bone microstructure changes. Silencing GRP78 substantially inhibits the migration and invasion of PCa cells in vitro and bone metastasis and tumor growth in vivo. Mechanistically, GRP78 promotes the migration and invasion of PCa cells via the Sonic hedgehog (Shh) signaling pathway. Cell co-culture showed that GRP78 promotes the differentiation of osteoblasts and osteoclasts through Shh signaling. Our findings suggest that tumor-bone matrix interactions owing to GRP78-activated paracrine Shh signaling by PCa cells regulate the differentiation of osteoblasts and osteoclasts. This process promotes bone metastasis and the proliferation of PCa cells in the bone microenvironment. Targeting the GRP78/Shh axis can serve as a therapeutic strategy to prevent bone metastasis and improve the quality of life of patients with PCa.

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.

INTRODUCTION: 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 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 types 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.

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.

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.

Effects of physical method and enzymatic hydrolysis on the properties of soybean fiber-rich stabilizer for oil in water emulsions.

BACKGROUND: Okara is a by-product from the soybean industry and an abundant resource of insoluble soybean fiber (ISF). ISF with various properties could be obtained by different extraction methods. It is an attractive option to utilize okara by taking advantage of ISF as an emulsifier or stabilizer. RESULTS: Compared with the untreated ISF (ISFUT ), superfine grinding reduced the particle size and viscosity of ISF (ISFSG ). Steam explosion increased the water solubility from 17.5% to 51.7% but decreased the water holding capacity and swelling capacity of ISF (ISFSE ) from 15.0 and 14.0 g/g to 4.2 and 3.3 g/g, respectively. Emulsions prepared by ISFUT and ISFSG before or after enzymatic hydrolysis presented large oil droplets and were unstable. Although emulsions prepared by ISFSE after enzymatic hydrolysis (ISFSE-E ) showed flocculation, the volume-weighted average diameter (19.7 µm) were the smallest while the viscosity and viscoelastic modulus were the highest, and exhibited excellent physical stability during storage. CONCLUSION: ISF obtained by physical and hydrolysis treatment displayed diverging physicochemical properties while ISF prepared by steam explosion-enzymatic hydrolysis presented the best potential to stabilize emulsions. The present study could provide novel information about the utilization of okara by the application of ISF as an emulsifier or stabilizer. © 2023 Society of Chemical Industry.

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.

Ankylosing spondylitis PET imaging and quantifications via P2X7 receptor-targeting radioligand [18F]GSK1482160.

PURPOSE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine; however, the quantitative detection of inflammation in AS remains a challenge in clinical settings. We aimed to investigate the feasibility of using a specific P2X7R-targeting 18F-labeled tracer [18F]GSK1482160 for positron emission tomography (PET) imaging and the quantification of AS. METHODS: The radioligand [18F]GSK1482160 was obtained based on nucleophilic aliphatic substitution. Dynamic [18F]GSK1482160 and [18F]FDG micro-PET/CT imaging were performed on AS mice (n = 8) and age-matched controls (n = 8). Tracer kinetics modeling was performed using Logan's graphical arterial input function analysis to quantify the in vivo expression of P2X7R. The post-PET tissues were collected for hematoxylin-eosin (H&E), immunohistochemical (IHC), and immunofluorescence (IF) staining. RESULTS: [18F]GSK1482160 PET/CT imaging revealed that the specific binding in the ankle joint and sacroiliac joint (SIJ) of the AS at 8 weeks group (BPNDankle-AS-8W (non-displaceable binding potential of the ankle) 3.931 ± 0.74; BPND SIJ-AS-8W (BPBD of the SIJ) 4.225 ± 0.84) were significantly higher than the controls at 8 weeks group (BPNDankle-Ctr-8W 0.325 ± 0.15, BPNDSJJ-Ctr-8W 0.319 ± 0.17) respectively, and the AS at 14 weeks group (BPNDankle-AS-14W 12.212 ± 2.25; BPNDSJJ-AS-14W 13.389 ± 3.60) were significantly higher than the controls at 14 weeks group (BPNDankle-Ctr-14W 0.204 ± 0.16, BPNDSJJ-Ctr-14W 0.655 ± 0.35) respectively. The four groups had no significant difference in the [18F]FDG uptake of ankle and SIJ. IHC and IF staining revealed that the overexpression of P2X7R was colocalized with activated macrophages from the ankle synovium and spinal endplate in mice with AS, indicating that quantification of P2X7R may contribute to the understanding of the pathogenesis of inflammation in human AS. CONCLUSION: This study developed a novel P2X7R-targeting PET tracer [18F]GSK1482160 to detect the expression of P2X7R in AS mouse models and provided powerful non-invasive PET imaging and quantification for AS.

Preparation and characterization of emulsion gels stabilized by adequately preprocessed insoluble soybean fiber from okara.

Emulsion gels as soft materials were formulated by insoluble soybean fiber (ISF) assembled from okara in this study. Steam explosion on okara (ISFS) transformed the insoluble fiber in the original okara (ISFU) into soluble fiber. Enzymatic hydrolysis led to a lower protein content, smaller particle size and smaller contact angle of ISF. ISFE, which was obtained by enzymatic hydrolysis of ISFU, was not able to produce stable emulsion gels at 0.50 to 1.50 wt% ISF, whereas the ISF after a combined steam explosion-enzymatic hydrolysis treatment (giving rise to ISFSE) stabilized emulsion gels at varying oil volume fractions (φ) from 10 to 50%. The ζ-potential of emulsion gels was around -19 to -26 mV. The droplet size first decreased (from 43.8 µm to 14.8 µm when at φ = 0.3) with increasing ISF content (from 0.25 wt% to 1.25 wt%) and then remained constant, as also seen from the microstructure. The apparent viscosity and viscoelastic properties were strengthened upon increasing both the ISF concentration and oil volume fraction. The protein and soluble fiber contributed to the interfacial activity of ISF while the insoluble fiber played an important role in the gel-like structured network of emulsion gels, making them maintain physical stability during long term storage. These findings could provide novel information about soybean fiber to fabricate soft materials and the utilization of okara at an industrial-scale.

Plasma anti-myosin autoantibodies in the diagnosis of necrotizing enterocolitis.

We aimed to assess whether autoantibodies can be used as biomarkers for necrotizing enterocolitis (NEC) and applied for its early diagnosis. A prospective observational study was conducted in neonates with suspected NEC abdominal distension (the developmental study), which consisted of 50 neonates finally divided into NEC (n = 24) and non-NEC (n = 26) cohorts based on follow-up results. Serum samples were collected within 48 h of illness onset and used for screening NEC-associated plasma autoantibodies by autoantigen microarray. Additionally, we validated anti-myosin autoantibodies by enzyme-linked immunosorbent assay (ELISA) in an independent validation study, for which we selected plasma samples within 48 h of onset of NEC (n = 38) and samples of gestational age- and weight-matched controls (n = 13). Autoantigen microarray revealed that both IgG and IgM anti-myosin autoantibodies in plasma from neonates with NEC were significantly higher than those in neonates with other diagnoses. ELISA showed that plasma anti-myosin autoantibodies increased in the NEC cohort, with 1.5-fold higher levels than in the non-NEC cohort. Anti-myosin autoantibodies were able to distinguish NEC from non-NEC, achieving an area under the curve (AUC) of 0.8856 (95% confidence interval (CI): 0.7918-0.9795), with sensitivity of 81.58% and specificity of 76.93%. Plasma anti-myosin autoantibodies were significantly higher in all three subtypes of NEC (P < 0.0001 for NEC I; P = 0.0018 for NEC II; P = 0.0011 for NEC III), especially in NEC stage I than that in the non-NEC controls. CONCLUSION: Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC, especially for NEC stage I. WHAT IS KNOWN: • Intestinal damage and self-antigen exposure may lead to increased autoantibodies, and they are widely used as biomarkers for diagnosing inflammatory bowel disease. • Necrotizing enterocolitis (NEC) is a devastating disease with overwhelming inflammation and immune dysregulation. WHAT IS NEW: • Increased autoantibodies were present in patients with NEC, even before typical X-ray manifestations. • Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC.

Emerging Human Fascioliasis: A Retrospective Study of Epidemiological Findings in Dali, Yunnan Province, China (2012-2021).

BACKGROUND Human fascioliasis is an emerging zoonotic disease caused by the trematodes, or flatworms, Fasciola hepatica and Fasciola gigantica, also known as liver flukes. This retrospective study aimed to report the epidemiological findings in 95 cases of human fascioliasis in Dali, Yunnan Province, southwestern China, diagnosed between 2012 and 2021. MATERIAL AND METHODS The epidemiologic and clinical data of 95 patients diagnosed with human fascioliasis in Dali area from January 2012 to December 2021 were collected and retrospectively analyzed. The diagnosis of fascioliasis was based on the Chinese National Standard of Diagnosis of Fascioliasis (WS/T566-2017). RESULTS The mean age of patients was 38.54±15.68 years, and there were more female patients than male (61.05% vs 38.95%). The high-incidence seasons were identified as summer and autumn. The patients with human fascioliasis lived in pastoral areas or were infected F. gigantica by consuming contaminated vegetables or water containing metacercaria. Meanwhile, human fascioliasis was diagnosed by positive serologic tests (1: 640), and Fasciola eggs (144-180×73-96 µm) were detected in stool samples of 6 patients. The most common clinical features were abdominal pain (70.53%), accompanied by elevated eosinophils in 89.5% of these patients. Antiparasitic treatment with triclabendazole at 10 mg/kg/day for 2 days led to symptom relief in all patients. CONCLUSIONS The findings from this observational epidemiological study have highlighted the importance of recognizing, diagnosing, and managing fascioliasis, which is an emerging zoonosis associated with increased human proximity to plant-eating domestic and farmed animals.

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.